NIR Fluorescent/Photoacoustic Bimodal Imaging of Ferroptosis in Pancreatic Cancer Using Biothiols-Activable Probes.

Ferroptosis modulation is a powerful therapeutic option for pancreatic ductal adenocarcinoma (PDAC) with a low 5-year survival rate and lack of effective treatment methods. However, due to the dual role of ferroptosis in promoting and inhibiting pancreatic tumorigenesis, regulating the degree of ferroptosis is very important to obtain the best therapeutic effect of PDAC. Biothiols are suitable as biomarkers of imaging ferroptosis due to the dramatic decreases of biothiol levels in ferroptosis caused by the inhibited synthesis pathway of glutathione (GSH) and the depletion of biothiol by reactive oxygen species. Moreover, a very recent study reported that cysteine (Cys) depletion can lead to pancreatic tumor ferroptosis in mice and may be employed as an effective therapeutic strategy for PDAC. Therefore, visualization of biothiols in ferroptosis of PDAC will be helpful for regulating the degree of ferroptosis, understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis, and further promoting the study and treatment of PDAC. Herein, two biothiol-activable near-infrared (NIR) fluorescent/photoacoustic bimodal imaging probes (HYD-BX and HYD-DX) for imaging of pancreatic tumor ferroptosis were reported. These two probes show excellent bimodal response performances for biothiols in solution, cells, and tumors. Subsequently, they have been employed successfully for real-time visualization of changes in concentration levels of biothiols during the ferroptosis process in PDAC cells and HepG2 cells. Most importantly, they have been further applied for bimodal imaging of ferroptosis in pancreatic cancer in mice, with satisfactory results. The development of these two probes provides new tools for monitoring changes in concentration levels of biothiols in ferroptosis and will have a positive impact on understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis and further promoting the study and treatment of PDAC.

In Situ-Grown 2D Perovskite Based on π-Conjugated Aggregation-Induced Emission Organic Spacer Boosting the Efficiency and Stability of 2D-3D Heterostructured Perovskite Solar Cells.

The two-dimensional-three-dimensional (2D-3D) heterostructured perovskite solar cells (PSCs) have drawn widespread interest, wherein the organic spacer plays a significant role in the photovoltaic performance. Herein, a novel π-conjugated organic spacer with the aggregation-induced emission (AIE) property, (Z)-2-([1,1'-biphenyl]-4-yl)-3-(5-(4-(3-aminopropoxy)phenyl)thiophen-2-yl)acrylonitrile (BPCSA-S), is designed and synthesized, which is successfully applied for the in situ construction of 2D-3D heterostructured PSCs via the two-step solution method. By virtue of the functional groups (i.e., cyano, thiophene, and amino) in BPCSA-S, the BPCSA-S organic spacer can trigger the in situ growth of 2D perovskites, which will serve as the template for the heteroepitaxial growth of 3D perovskites, thus obtaining a 2D-3D heterostructured film with high-quality and few defects. More pleasingly, benefiting from the AIE property and delocalized π-electrons in the π-conjugated BPCSA-S organic spacer, excellent photosensitization process and carrier transport can be achieved. Consequently, the resultant 2D-3D heterostructured PSCs yield a pleasing PCE of 22.07%, accompanied by mitigatory hysteresis, as well as enhanced stability. Our research shows a hopeful multifunctional organic spacer approach using the novel π-conjugated AIE organic spacer for high-performance PSCs.

Direct in situ photolithography of ultra-stable CsPbBr3 quantum dot arrays based on crosslinking polymerization.

CsPbX3 (X = Br, Cl, I) perovskite quantum dots (PQDs) are the rising star for various display applications owing to their excellent opto-electrical properties, such as an adjustable spectrum, narrow emission linewidth and high quantum yield. However, these PQDs are well known to suffer from intrinsic instability under atmospheric conditions. In this work, a novel photosensitive ligand, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (XBPO), was employed as a dual-functional reagent for PQD surface engineering. The XBPO ligand could cleave to produce phenylphosphinyl radicals and trimethylbenzoyl radicals under UV light irradiation. The phenylphosphinyl radicals with PO bonds could effectively passivate the PQD surface defects, leading to quantum yield improvement. The CsPbBr3 and CsPbI3 PQDs with XBPO modification could achieve a photoluminescence quantum yield (PLQY) of near unity and 92%, respectively. Additionally, the in situ encapsulation of the PQDs was achieved by the subsequent crosslinking polymerization, which significantly improved the stability of the PQDs against solvents and the environment. By combining a standard photolithography procedure, we demonstrated a micro-pattern of CsPbBr3 PQDs. These results establish a universal route for PQD patterning, compatible with the existing photolithography processes, which could facilitate the application of PQDs in next-generation display technology.

Reaction-Activated Disassembly of the NIR-II Probe Enables Fast Detection and Ratiometric Photoacoustic Imaging of Glutathione In Vivo.

Glutathione (GSH), the most abundant nonprotein biothiol, is a significant endogenous molecule that plays a key role in redox equilibrium in vivo and is regarded as a critical biomarker of cancer. Currently, various fluorescent probes have been designed and synthesized for imaging GSH at the cellular level in the visible range and the first near-infrared window (NIR-I, 750-900 nm). However, the application of these fluorescent probes for bioimaging and biosensing in vivo has been extremely hindered by the high biobackground and low tissue penetration. Herein, based on the self-assembly and disassembly of J-aggregation, we designed and synthesized a GSH-activatable probe MC-PSE for second near-infrared window (NIR-II) fluorescence and ratiometric photoacoustic imaging of GSH in vivo. The anionic cyanine-based MC-PSE tends to form stable J-aggregates in an aqueous solution. Upon the reaction with GSH, the J-aggregates of MC-PSE disassembled, the emission peak intensity of MC-PSE at 940 nm significantly increased by about 20 times, and the PA900/PA980 ratio increased by 4 times within 15 min in vitro. Notably, we used MC-PSE to visualize GSH in tumor-bearing mice and to distinguish normal and tumor areas successfully by virtue of NIR-II FL and PA dual-modal imaging. The design strategy of MC-PSE provides a novel method for ratiometric photoacoustic imaging, and MC-PSE is expected to be a powerful tool for the accurate detection of GSH in cancer diagnosis.

A Quencher-Based Blood-Autofluorescence-Suppression Strategy Enables the Quantification of Trace Analytes in Whole Blood.

Precise quantification of trace components in whole blood via fluorescence is of great significance. However, the applicability of current fluorescent probes in whole blood is largely hindered by the strong blood autofluorescence. Here, we proposed a blood autofluorescence-suppressed sensing strategy to develop an activable fluorescent probe for quantification of trace analyte in whole blood. Based on inner filter effect, by screening fluorophores whose absorption overlapped with the emission of blood, a redshift BODIPY quencher with an absorption wavelength ranging from 600-700 nm was selected for its superior quenching efficiency and high brightness. Two 7-nitrobenzo[c] [1,2,5] oxadiazole ether groups were introduced onto the BODIPY skeleton for quenching its fluorescence and the response of H2 S, a gas signal molecule that can hardly be quantified because of its low concentration in whole blood. Such detection system shows a pretty low background signal and high signal-to-back ratio, the probe thus achieved the accurate quantification of endogenous H2 S in 20-fold dilution of whole blood samples, which is the first attempt of quantifying endogenous H2 S in whole blood. Moreover, this autofluorescence-suppressed sensing strategy could be expanded to other trace analytes detection in whole blood, which may accelerate the application of fluorescent probes in clinical blood test.

In situ detection of alkaline phosphatase in a cisplatin-induced acute kidney injury model with a fluorescent/photoacoustic bimodal molecular probe.

Kidneys play an important part in drug metabolism and excretion. High local concentration of drugs or drug allergies often cause acute kidney injury (AKI). Identification of effective biomarkers of initial stage AKI and constructing activable molecular probes with excellent detection properties for early evaluation of AKI are necessary, yet remain significant challenges. Alkaline phosphatase (ALP), a key hydrolyzing protease, exists in the epithelial cells of the kidney and is discharged into the urine following kidney injury. However, no studies have revealed its level in drug-induced AKI. Existing ALP fluorescent molecular probes are not suitable for testing and imaging of ALP in the AKI model. Drug-induced AKI is accompanied by oxidative stress, and many studies have indicated that a large increase in reactive oxygen species (ROS) occur in the AKI model. Thus, the probe used for imaging of AKI must be chemically stable in the presence of ROS. However, most existing near-infrared fluorescent (NIRF) ALP probes are not stable in the presence of ROS in the AKI model. Hence, we built a chemically stable molecular sensor (CS-ALP) to map ALP level in cisplatin-induced AKI. This novel probe is not destroyed by ROS generated in the AKI model, thus allowing high-fidelity imaging. In the presence of ALP, the CS-ALP probe generates a new absorbance peak at 685 nm and a fluorescent emission peak at 716 nm that could be used to "turn on" photoacoustic (PA) and NIRF imaging of ALP in AKI. Levels of CS-ALP build up rapidly in the kidney, and CS-ALP has been successfully applied in NIRF/PA bimodal in vivo imaging. Through the NIRF/PA bimodal imaging results, we demonstrate that upregulated expression of ALP occurs in the early stages of AKI and continues with injury progression.

Defects enriched cobalt molybdate induced by carbon dots for a high rate Li-ion battery anode.

A defects-enriched CoMoO4/carbon dot (CD) with CoMoO4around 37 nm is achieved via hydrothermal reaction by introducing CDs to buffer large volume changes of CoMoO4during lithiation-delithiation and enhance rate performance. The phase, morphology, microstructure, as well as the interface of the CoMoO4/CD composites were investigated by x-ray diffraction, scanning electron microscopy, transmission electron microscopy and x-ray photoelectron spectroscopy. When employed as Li-ion battery anode, the CoMoO4/CD exhibits a reversible capacity of ∼531 mAh g-1after 400 cycles at a current density of 2.0 A g-1. Under the scan rate at 2 mV s-1, the CoMoO4/CD shows accounts for 81.1% pseudocapacitance. It may attribute to the CoMoO4with surface defects given more reaction sites to facilitate electrons and lithium ions transfer at high current densities. Through galvanostatic intermittent titration technique, the average lithium ion diffusion coefficient calculated is an order of magnitude larger than that of bulk CoMoO4, indicating that the CoMoO4/CD possesses promising electrons and lithium ions transportation performance as anode material.

Synthesis and utilization of Co3O4 doped carbon nanofiber for fabrication of hemoglobin-based electrochemical sensor.

In this paper cobalt oxide (Co3O4) nanoparticles were mixed with polyacrylonitrile to prepare Co3O4 doped carbon nanofiber (CNF) composite by electrospinning and carbonization, which was further used to modify on carbon ionic liquid electrode (CILE). Hemoglobin (Hb) was immobilized on Co3O4-CNF/CILE surface with Nafion acted as the protective film to fabricate an electrochemical biosensor (Nafion/Hb/Co3O4-CNF/CILE). Electrochemical behavior of Hb on the electrode was investigated with a pair of quasi-reversible redox peak appeared on cyclic voltammogram and electrochemical parameters were calculated. Moreover, this biosensor had good analytical capabilities for electrocatalytic reduction of different substrates including trichloroacetic acid, potassium bromate and sodium nitrite with wider detection range from 40.0 to 260.0 mmol L-1, 0.1 to 48.0 mmol L-1 and 1.0 to 12.0 mmol L-1 by cyclic voltammetry, respectively. The proposed method showed excellent anti-interferences ability with good selectivity and was successful used for quantitative detection of real samples, which displayed the potential applications to develop into a new analytical device.

Proton transfer reactions of methylanthracene radical cations with nitrogen-centered bases under non-steady-state conditions. a search for the possible effect of reactant impurities upon the kinetic data.

[reaction: see text] At a recent conference, the issue was raised that our earlier non-steady-state kinetic studies(1)(-)(3) may be in error because of the effects of possible impurities in the N-centered bases employed. This prompted our reinvestigation of these systems with that possibility in mind. It was pointed out that in a series of reactions, if a reactive impurity affects the kinetics in one reaction, then it would exert a consistent effect on the kinetics of all of the reactions in the series. Experimental data for three different series of reactions, proton transfer reactions of 2,6-dimethylpyridine, 2,6-diethylpyridine, and 2,6-diphenylpyridine with four different methylanthracene radical cations, were concurrently examined for possible reactant impurity problems. The analysis confirms that the simulated data for the simple second-order mechanism in the presence of a reactive impurity do not fit experimental data for the proton transfer reactions. The hypothesis that deviations from simple second-order kinetics are caused by the presence of reactive impurities is not valid. It was concluded that the presence of reactive impurities was not a significant problem in the studies of proton transfer reactions of methylanthracene radical cations with pyridine bases.

Resolution of the non-steady-state kinetics of the elimination of HBr from 2-(p-nitrophenyl)ethyl bromide in alcohol/alkoxide media.

Non-steady-state kinetic studies reveal that the elimination of HBr from 2-(p-nitrophenyl)ethyl bromide in alcohol/alkoxide media, the classical concerted E2 reaction, actually takes place by a two-step mechanism involving the intermediate formation of the carbanion.

Hydride-exchange reactions between NADH and NAD+ model compounds under non-steady-state conditions. Apparent and real kinetic isotope effects.

The kinetics of the hydride exchange reaction between NADH model compound 10-methyl-9,10-dihydroacridine (MAH) and 1-benzyl-3-cyanoquinolinium (BQCN+) ion in acetonitrile were studied at temperatures ranging from 291 to 325 K. The extent of reaction-time profiles during the first half-lives are compared with theoretical data for the simple single-step mechanism and a 2-step mechanism involving initial donor/acceptor complex formation followed by unimolecular hydride transfer. The profiles for the reactions of MAH deviate significantly from those expected for the simple single-step mechanism with the deviation increasing with increasing temperature. The deviation from simple mechanism behavior is much less pronounced for the reactions of 10-methyl-9,10-dihydroacridine-10,10-d2 (MAD) which gives rise to extent of reaction dependent apparent kinetic isotope effects (KIEapp). Excellent fits of the experimental extent of reaction-time profiles with theoretical data for the 2-step mechanism, in the pre-steady-state time period, were observed in all cases. Resolution of the kinetics of the hydride exchange reaction into the microscopic rate constants over the entire temperature range resulted in real kinetic isotope effects for the hydride transfer step ranging from 40 (291 K) to 8.2 (325 K). That the reaction involves significant hydride tunnelling was verified by the magnitudes of the Arrhenius parameters; Ea D - EaH = 8.7 kcal mol-1 and AD/AH = 8 x 10(4). An electron donor acceptor complex (lambda max = 526 nm) was observed to be a reaction intermediate. Theoretical extent of reaction-time profile data are discussed for the case where a reaction intermediate is formed in a non-productive side equilibrium as compared to the case where it is a real intermediate on the reaction coordinate between reactants and products. The common assumption that the two cases are kinetically indistinguishable is shown to be incorrect.