Mechanism of SO2/H2O enhanced rare earth tailings catalysts in NH3-SCR at medium and high temperature.

Rare earth tailings (RET) NH3-SCR catalysts were prepared by mechanical and microwave activation of a large amount of rare earth tailings after beneficiation of Bayan Ebo rare earth ore. The effects of SO2/H2O on the denitrification performance of the RET catalysts were evaluated by conducting denitrification activity tests, SO2/H2O tolerance tests and in situ DRIFTs mechanistic analysis. The results showed that the denitrification activity was significantly increased in the presence of SO2/H2O. And in situ DRIFTs analysis showed that in the presence of SO2/H2O, SO2 could be adsorbed as SO32- groups by the hydroxyl groups on the catalyst surface and react with SO42- to form S2O72- species. And in the presence of NH3, S2O72- would decompose into unstable SO42- species and SO32- and continue to react cyclically to form S2O72- species, providing the RET catalyst provides more acid sites, facilitating the SCR reaction.

Combination of two-photon fluorescent probes for carboxylesterase and ONOO- to visualize the transformation of nonalcoholic fatty liver to nonalcoholic steatohepatitis in liver orthotopic imaging.

As the most common cause of liver diseases, nonalcoholic fatty liver disease (NAFLD) can be classified into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). While NAFL is generally benign, the transition from NAFL to NASH is a cardinal feature of the non-benign liver disease that leads to cirrhosis and cancer, which indicates that tracking the transformation of NAFL to NASH timely is significant for precision management of liver diseases. Therefore, two fluorescent probes (CNFCl and DRNO) have been developed to visualize this pathological event. α-Fluorochloroacetamide and α-ketoamide was employed as the recognition site for carboxylesterase (CE) in CNFCl and peroxynitrite (ONOO-) in DRNO, respectively. CNFCl (λem = 445 nm) and DRNO (λem = 560 nm) showed high specificity and sensitivity towards CE and ONOO- respectively. By incubating with CE/ONOO- for 0.5 h respectively, both the emission intensity of CNFCl (linear range: 0-0.2 U/mL) and DRNO (linear range: 0-17.5 µM) displayed significant enhancement. As a result, the detection limit of CNFCl and DRNO for CE and ONOO- was calculated as 4.2 mU/L and 0.05 µM respectively. More importantly, the emission spectra of CNFCl and DRNO in the presence of CE and ONOO- respectively were cross-talk free under the two-photon excitation of 720 nm. This greatly facilitated the simultaneous detection of CE and ONOO- at distinctive channel, thus ensuring the high fidelity of the detection. These two probes were combined to image the fluctuation of CE and ONOO- during the conversion of NAFL to NASH in vitro and in vivo. It was found that while CE displayed a tendency to rise and then reduce during the transition from NAFL to NASH, ONOO- increased continuously, confirming that the combined imaging by CNFCl and DRNO might visualize the transformation of NAFL to NASH. The results provide robust visual tool to decipher the relationship between the stage of NAFLD and the level of CE/ONOO-. We anticipate this study may open new avenues to distinguish NASH from NAFL, which may further promote the study of intracellular biological activities of CE and the development of NAFLD diagnostic methods.

Bio-orthogonally Activatable Fluorescent Probe for Specific Imaging of Myeloid Cell Leukemia 1 Protein.

The antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) has been increasingly identified as a promising potential therapeutic target attributed to its critical regulation effect in diverse cellar physiopathological events. Current fluorescence imaging strategies tend to be susceptible to the cellular microenvironment, and straightforward mapping of Mcl-1's level variation remains challenging. In this paper, an activatable "off-on" fluorescence strategy for Mcl-1 specific labeling was presented based on bio-orthogonal chemistry by introducing tetrazine-functionalized borondipyrromethene (TB) as a fluorescent reporter and trans-cyclooctyne-derived indole-2-carboxylic acid (TI) as an Mcl-1 targeting moiety. With the click pair of TB and TI, the Mcl-1 expression level in vitro and in vivo was successfully mapped straightforward. Also, the level changes of Mcl-1 upon drug challenge were demonstrated. This work provides a robust fluorescence strategy for Mcl-1 in situ imaging, and the results would further facilitate the comprehensive revelation of the Mcl-1 biological effect.

Exploration of Thermally Activated Delayed Fluorescence (TADF)-Based Photoredox Catalyst To Establish the Mechanisms of Action for Photodynamic Therapy.

The mechanisms of action (MoA) have been proposed to further reduce the O2 dependence of photodynamic therapy (PDT) significantly. However, the triplet states of traditional photosensitizers are relatively short and also are easily deactivated by the quenching of H2O or O2. This is not conducive for the electron transfer in the photocatalytic process and poses a great obstacle to establish the MoA. Therefore, we selected and synthesized a zirconium(IV) complex (Zr(MesPDPPh)2) reported by Milsmann to address this issue. The specific symmetric and intact geometry endowed Zr(MesPDPPh)2 NPs with long-lived triplet excited state (τ = 350 µs), desired sensitized ability, and improved anti-interfering performance on O2, which was matched with the requirements of photoredox catalyst significantly. The results showed that while PDT (I) and PDT (II) could be achieved simultaneously by leveraging Zr(MesPDPPh)2 NPs, it also could be served as a rare example of thermally activated delayed fluorescence (TADF)-based photoredox catalyst to implement the MoA of PDT. It involved the oxidation of NADH and the establishment of catalytic cycle collaborating by O2 and cytochrome c (cyt c) in normoxia and hypoxia, respectively. As a result, the oxygen-free PDT and tumor-growth inhibition was realized.

In Situ Fluorescence Imaging Reveals Contribution of Cerebral Hydroxyl Radicals in Hyperhomocysteinemia-Induced Alzheimer-like Dementia.

Elevated plasma level of homocysteine, also termed as hyperhomocysteinemia, is acknowledged as a significant and independent risk factor of Alzheimer's disease. However, the mechanistic insight has not been thoroughly elucidated yet. In this work, 3,5-dihydroxybenzyloxy was explored as the unique reaction trigger and integrated into the naphthalimide fluorophore via a carbamate linker to afford a new probe for •OH imaging. •OH treatment induced aromatic hydroxylation and subsequent elimination reaction to release the caged fluorophore, accompanied with a highly specific and sensitive turn-on fluorescence response. Cell imaging results revealed that excess homocysteine triggered overwhelming •OH production, which was mediated by N-methyl-d-aspartate receptor and NADPH oxidase, and the resultant •OH stress further initiated neuronal ferroptosis, also confirmed by western blot analyses. Additionally, hyperhomocysteinemic mouse models were established, and Alzheimer-like dementia of the mice was observed from behavioral tests. Most importantly, with this probe, cerebral •OH fluctuation was in situ visualized in live mice, which positively correlated with the severity of Alzheimer-like dementia induced by hyperhomocysteinemia. These results reveal that cerebral •OH stress may be the critical nexus linking hyperhomocysteinemia and Alzheimer's disease. This work provides a robust fluorescence probe for in situ visualizing the cerebral •OH fluctuations and illuminating critical insights into •OH contributions in brain disorders.

Endoplasmic Reticulum-Targeted Carbon Monoxide Photoreleaser for Drug-Induced Hepatotoxicity Remediation.

The alleviation of drug-induced liver injury has been a long-term public health concern. Growing evidence suggests that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of drug-induced hepatotoxicity. Therefore, the inhibition of ER stress has gradually become one of the important pathways to alleviate drug-induced liver injury. In this work, we developed an ER-targeted photoreleaser, ERC, for controllable carbon monoxide (CO) release with a near-infrared light trigger. By employing peroxynitrite (ONOO-) as an imaging biomarker of hepatotoxicity, the remediating effect of CO was mapped upon drug acetaminophen (APAP) challenge. The direct and visual evidence of suppressing oxidative and nitrosative stress by CO was obtained both in living cells and in mice. Additionally, the ER stress inhibiting the effect of CO was verified during drug-induced hepatotoxicity. This work demonstrated that CO may be employed as a potent potential antidote for APAP-related oxidative and nitrative stress remediation.

Real-time visualization of the fluctuations in HOBr with AIE fluorescent probes during myocardial ischemia-reperfusion injury.

Two fluorescent probes (QM-S and QM-Se) featuring AIE properties were developed. The increased intracellular hypobromous acid (HOBr) in cardiomyocytes during MIRI was revealed with these probes. It was also observed that MIRI might be alleviated by combating oxidative stress, as well as inhibiting inflammation and ferroptosis, which could mediate oxidative stress.

Cyano-substituted stilbene (CSS)-based conjugated polymers: Photophysical properties exploration and applications in photodynamic therapy.

Conjugated polymers (CPs) have attracted great attention due to their excellent optical properties (such as large absorption cross section, signal amplification, high photostability etc.). As representative electron acceptors and organic small molecules which are easy to be synthesized and modified, cyano-substituted stilbene (CSS) derivatives are widely used to construct photoelectrical materials. Despite donor-acceptor (D-A) conjugated polymers based on CSS have been applied in sensing and super-resolution imaging, systematic studies about the effects of different CSS structures on the photophysical properties of CPs have rarely been reported. Therefore, we have synthesized a series of D-A conjugated polymer nanoparticles (CP NPs) based on different CSS units, and found that the photophysical properties of CP NPs including the bandgap and ΔES-T were closely associated with the structure of CSS derivatives. Moreover, the introduction of tetraphenylethylene (TPE) can relieve the aggregation-caused quenching (ACQ) effects of CSS conjugated polymers to varying degrees. The theoretical calculation further corroborated that by regulating the number and distribution of cyanide groups in the repeating units, the stronger D-A strength resulted in a redshift in the emission spectrum and the more efficient capacity of total ROS (1O2, O2•- and •OH) generation. We then selected CP6-TAT NPs, with the near infrared (NIR) emission and best ФPS, to characterize its performance in photodynamic therapy (PDT). It was revealed that CP6-TAT NPs can be regarded as an ideal candidate for PDT. The results provided a new reference for regulating the structure-effect relationship of CPs and a comprehensive method for constructing photosensitizers based on CPs.

Two-photon fluorescence imaging of the cerebral peroxynitrite stress in Alzheimer's disease.

We designed and synthesized an oxindole-functionalized two-photon fluorescent probe based on a naphthalimide fluorophore, which enabled in situ visualization of the overwhelming peroxynitrite flux during amyloid-ß-induced neuronal ferroptosis and cerebral peroxynitrite stress in live mice with Alzheimer's disease.

Fabricating and Modulating Robust Multi-Photoaddressable Systems with the Derivatives of Diarylethylene and Donor-Acceptor Stenhouse Adducts.

Multi-photoaddressable systems (MPSs) belong to complex systems, which are comprised of more than one photoswitching molecule and can respond to different wavelengths of light simultaneously. While MPSs have been extensively applied in various fields, there are also some challenges, such as the deficiency of the wavelength-selective control and the interference from the poor thermodynamic stability of used photoswitching molecules. Herein, we reported two robust MPSs (MPS1/2) consisting of diarylethylene derivative (DAE) and different donor-acceptor Stenhouse adducts (DASAs), in which both opened and closed forms of DAE and opened forms of DASAs are thermodynamically stable. MPS1/2 enable fully reversible cyclic photoswitching with improved thermal interference resistance. Moreover, MPS2 also shows a favorable property in PMMA films and has been applied in multicolor display. It is expected that the prepared MPSs could be used in more fields such as information storage and reading and encoding light.

Harnessing SeN to develop novel fluorescent probes for visualizing the variation of endogenous hypobromous acid (HOBr) during the administration of an immunotherapeutic agent.

By means of the formation of SeN, the ABT-Se and NDI-Se were developed to detect and visualize endogenous hypobromous acid (HOBr) in live cells. Specifically, the upregulation of HOBr was monitored by NDI-Se during the administration of an immunotherapeutic agent.

Dual-Channel Imaging of Amyloid-ß Plaques and Peroxynitrite To Illuminate Their Correlations in Alzheimer's Disease Using a Unimolecular Two-Photon Fluorescent Probe.

Alzheimer's disease (AD) involves multiple pathological factors that mutually cooperate and closely contact to form interaction networks for jointly promoting the AD progression. Therefore, the comonitoring of different factors is particularly valuable for elucidating their level dynamics and complex interactions. However, such significant investigations remain a major challenge due to the lack of unimolecular fluorescent probes capable of simultaneous and discriminative visualization of multiple targets. To address this concern, as proof of principle, we rationally designed a unimolecular fluorescent probe to discriminate and simultaneously profile amyloid-ß (Aß) plaques and peroxynitrite (ONOO-), which are both the pronounced AD pathological factors. Herein, a novel ONOO- reaction trigger was installed onto an Aß plaque binding fluorophore to generate a dual functional fluorescent probe, displaying completely separate spectral responses to Aß plaques and ONOO- with high selectivity and sensitivity. With this probe, for the first time, we comonitored the distribution and variation of Aß plaques and ONOO- through two independent fluorescence channels, demonstrating their close apposition and tight correlation during AD course in live cell and mouse models through two-photon imaging mode. Notably, Aß aggregates induce the neuronal ONOO- generation, which conversely facilitates Aß aggregation. The two critical events, ONOO- stress and Aß aggregation, mutually amplify each other through positive feedback mechanisms and jointly promote the AD onset and progression. Furthermore, by coimaging of the level dynamics of Aß plaques and ONOO-, we found that the cerebral ONOO- is a potential biomarker, which emerges earlier than Aß plaques in transgenic mouse models. Overall, the dual-channel responsive performance renders this probe as a powerful imaging tool to decipher Aß plaque-ONOO- interactions, which will facilitate AD-associated molecular pathogenesis elucidation and multitarget drug discovery.

A light-activatable photosensitizer for photodynamic therapy based on a diarylethene derivative.

Herein, a light-activatable photosensitizer based on a diarylethene derivative, DAE-TPE, was developed for photodynamic therapy. Upon UV exposure, the "opened" form (OF) of DAE-TPE NPs was converted to the "closed" form (CF), and photosensitization was activated. The CF of DAE-TPE NPs exhibited sufficient photodynamic therapy effects upon HeLa cells.

A near-infrared fluorogenic probe for nuclear thiophenol detection.

Based on the thiolysis of dinitrophenyl ethers, a nucleus-targeted fluorescent probe, AQD, with bisalkylaminoanthraquinone as the fluorophore, was prepared for the near-infrared mapping of thiophenol in live cells, zebrafish, and mice.

An H2S-activated ratiometric CO photoreleaser enabled by excimer/monomer conversion.

Based on the excimer-monomer conversion of a pyrene-flavone hybrid, a ratiometric CO photoreleaser, PFN, was constructed for simultaneous H2S quantification and CO release in inflammatory cells.

Visualizing peroxynitrite fluxes in myocardial cells using a new fluorescent probe reveals the protective effect of estrogen.

A tetraphenyl ethylene (TPE)-based fluorescent probe specific for ONOO- was developed to evaluate and verify the protective effect of estrogen on myocardial cells during OGD/R.

Reactivity Modulation of Benzopyran-Coumarin Platform by Introducing Electron-Withdrawing Groups: Specific Detection of Biothiols and Peroxynitrite.

A variety of fluorophores have been designed and created to fabricate organic fluorescent probes. Among these fluorophores, benzopyran-coumarin (BC) based fluorescent platform has attracted increasing attention as it shows multiple appropriate fluorescent and imaging capacities. Nevertheless, the analytical potential of BC is still urgently needed to be further excavated as its detection performance is hindered by the inherent drawbacks of current BC skeleton, that is, limited number of reactive sites. As such, in this work, by simply introducing electron-withdrawing (EW) substituent groups, we reconstructed BC skeleton to afford two fluorescent probes, BCB (-Br substitued) and BCN (-NO2 substitued), both of which featured two highly reactive sites. These two probes were capable of detecting peroxynitrite (ONOO-) and biothiols (hydrogen sulfide, glutathione, cysteine, and homocysteine) through naked eye and UV-vis absorption analysis in buffer solution. In addition, BCB was able to specifically sense biothiols with fluorescent analysis while BCN, with - NO2 instead of -Br, displayed more prominent fluorescent specificity toward ONOO-. This work provided a new strategy for the reactivity regulation of fluorophore through EW group introduction, as well as an alternative approach and method for the construction of fluorescent probes for other important biological species.

A Facile, Versatile, and Highly Efficient Strategy for Peroxynitrite Bioimaging Enabled by Formamide Deformylation.

Peroxynitrite (ONOO-) is attracting increasing attention due to its involvement in multiple facets of pathophysiological processes. However, ONOO- bioimaging is still challenging due to (1) the lack of highly specific reaction triggers, (2) the tedious and low-yielding synthesis of current sophisticated probes, and (3) the lack of availability of a versatile chemical strategy. To address these challenges, on the basis of amine formylation/deformylation chemistry, we have developed a novel strategy for ONOO- bioimaging. As proof of principle, we designed, synthesized, and evaluated four novel fluorescent probes equipped with the formamide functionality. Although they feature distinctly different fluorophore classes, all probes can be synthesized in one step in high yields and exhibit particularly specific, highly sensitive, and rapid responses to ONOO-. The bioimaging capability is well demonstrated by successfully visualizing ONOO- fluctuation in live cells and major organs of mice suffering from paraquat poisoning. The proposed strategy has proved to be a facile, versatile, and highly efficient methodology for ONOO- visualization, which will greatly facilitate ONOO- biochemistry and pathophysiology.

A two-photon fluorescent probe for ratiometric visualization of hypochlorous acid in live cells and animals based on a selenide oxidation/elimination tandem reaction.

Utilizing the oxidation/elimination tandem reaction of the α-phenylseleno carbonyl moiety, a two-photon fluorescent probe for ratiometric visualization of hypochlorous acid was developed. Its superior sensing performance and practical applications were well demonstrated.

Mitochondrial Peroxynitrite Mediation of Anthracycline-Induced Cardiotoxicity as Visualized by a Two-Photon Near-Infrared Fluorescent Probe.

Anthracyclines rank among the most efficacious anticancer medications. However, their clinical utility and oncologic efficacy are severely compromised by the cardiotoxicity risk facing the early-diagnosis difficulty and their unclear molecular mechanism. Herein, a two-photon-excitable and near-infrared-emissive fluorescent probe, TPNIR-FP, was fabricated and endowed with extraordinary specificity and sensitivity and a rapid response toward peroxynitrite (ONOO-), as well as mitochondria-targeting ability. With the aid of TPNIR-FP, we demonstrate that mitochondrial ONOO- is upregulated in the early stage and contributes to the onset and progression of anthracycline cardiotoxicity in cardiomyocyte and mouse models; therefore, it represents an early biomarker to predict subclinical cardiotoxicity induced by drug challenge. Furthermore, TPNIR-FP is proved to be a robust imaging tool to provide critical insights into drug-induced cardiotoxicity and other ONOO--related pathophysiological processes.