White-light activatable organic NIR-II luminescence nanomaterials for imaging-guided surgery.

While second near-infrared (NIR-II) fluorescence imaging is a promising tool for real-time surveillance of surgical operations, the previously reported organic NIR-II luminescent materials for in vivo imaging are predominantly activated by expensive lasers or X-ray with high power and poor illumination homogeneity, which significantly limits their clinical applications. Here we report a white-light activatable NIR-II organic imaging agent by taking advantages of the strong intramolecular/intermolecular D-A interactions of conjugated Y6CT molecules in nanoparticles (Y6CT-NPs), with the brightness of as high as 13315.1, which is over two times that of the brightest laser-activated NIR-II organic contrast agents reported thus far. Upon white-light activation, Y6CT-NPs can achieve not only in vivo imaging of hepatic ischemia reperfusion, but also real-time monitoring of kidney transplantation surgery. During the surgery, identification of the renal vasculature, post-reconstruction assessment of renal allograft vascular integrity, and blood supply analysis of the ureter can be vividly depicted by using Y6CT-NPs with high signal-to-noise ratios upon clinical laparoscopic LED white-light activation. Our work provides efficient molecular design guidelines towards white-light activatable imaging agent and highlights an opportunity for precision imaging theranostics.

Multi-Functional 2D Covalent Organic Frameworks with Diketopyrrolopyrrole as Electron Acceptor.

2D covalent organic framework (COF) materials with extended conjugated structure and periodic columnar π-arrays exhibit promising applications in organic optoelectronics. However, there is a scarcity of reports on optoelectronic COFs, mainly due to the lack of suitable π-skeletons. Here, two multi-functional optoelectronic 2D COFs DPP-TPP-COF and DPP-TBB-COF are constructed with diketopyrrolopyrrole as electron acceptor (A), and 1,3,6,8-tetraphenylpyrene and 1,3,5-triphenylbenzene as electron donor (D) through imine bonds. Both 2D COFs showed good crystallinities and AA stacking with a rhombic framework for DPP-TPP-COF and hexagonal one for DPP-TBB-COF, respectively. The electron D-A and ordered intermolecular packing structures endow the COFs with broad UV-vis absorptions and narrow bandgaps along with suitable HOMO/LUMO energy levels, resulting in multi-functional optoelectronic properties, including photothermal conversion, supercapacitor property, and ambipolar semiconducting behavior. Among them, DPP-TPP-COF exhibits a high photothermal conversion efficiency of 47% under 660 nm laser irradiation, while DPP-TBB-COF exhibits superior specific capacitance of 384 F g-1. Moreover, P-type doping and N-type doping are achieved by iodine and tetrakis(dimethylamino)ethylene on a single host COF, resulting in ambipolar semiconducting behavior. These results provide a paradigm for the application of multi-functional optoelectronic COF materials.

Aggregation-Induced Emission (AIE), Life and Health.

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

A Highly Water-Soluble Aggregation-Induced Emission Luminogen with Anion-π+ Interactions for Targeted NIR Imaging of Cancer Cells and Type†I Photodynamic Therapy.

The low oxygen dependence of type I photosensitizers (PSs) has made them a popular choice for treating solid tumors. However, the drawbacks of poor water solubility, short emission wavelength, poor stability, and inability to distinguish cancer cells from normal cells limit the application of most type I PSs in clinical therapy. Thereby, developing novel type I PSs for overcoming these problems is an urgent but challenging task. Herein, by utilizing the distinctive structural characteristics of anion-π+ interactions, a highly water-soluble type I PS (DPBC-Br) with aggregation-induced emission (AIE) characteristic and near-infrared (NIR) emission is fabricated for the first time. DPBC-Br displays remarkable water solubility (7.3 mM) and outstanding photobleaching resistance, enabling efficient and precise differentiation between tumor cells and normal cells in a wash-free and long-term tracking manner via NIR-I imaging. Additionally, the superior type I reactive oxygen species (ROS) produced by DPBC-Br provide both specific killing of cancer cells in vitro and inhibition of tumor growth in vivo, with negligible systemic toxicity. This study rationally constructs a highly water-soluble type I PS, which has higher reliability and controllability compared with conventional nanoparticle formulating procedures, offering great potential for clinical cancer treatment.

Oxidization enhances type I ROS generation of AIE-active zwitterionic photosensitizers for photodynamic killing of drug-resistant bacteria.

Type I photosensitizers (PSs) with an aggregation-induced emission (AIE) feature have received sustained attention for their excellent theranostic performance in the treatment of clinical diseases. However, the development of AIE-active type I PSs with strong reactive oxygen species (ROS) production capacity remains a challenge due to the lack of in-depth theoretical studies on the aggregate behavior of PSs and rational design strategies. Herein, we proposed a facile oxidization strategy to enhance the ROS generation efficiency of AIE-active type I PSs. Two AIE luminogens, MPD and its oxidized product MPD-O were synthesized. Compared with MPD, the zwitterionic MPD-O showed higher ROS generation efficiency. The introduction of electron-withdrawing oxygen atoms results in the formation of intermolecular hydrogen bonds in the molecular stacking of MPD-O, which endowed MPD-O with more tightly packed arrangement in the aggregate state. Theoretical calculations demonstrated that more accessible intersystem crossing (ISC) channels and larger spin-orbit coupling (SOC) constants provide further explanation for the superior ROS generation efficiency of MPD-O, which evidenced the effectiveness of enhancing the ROS production ability by the oxidization strategy. Moreover, DAPD-O, a cationic derivative of MPD-O, was further synthesized to improve the antibacterial activity of MPD-O, showing excellent photodynamic antibacterial performance against methicillin-resistant S. aureus both in vitro and in vivo. This work elucidates the mechanism of the oxidization strategy for enhancing the ROS production ability of PSs and offers a new guideline for the exploitation of AIE-active type I PSs.

Acene enlargement for absorption red-shifting and photosensitization enhancement of photosensitizers with aggregation-induced emission.

Photosensitizers with aggregation-induced emission (AIE PSs) were widely explored in photodynamic therapy. Numerous acceptors but few donors were reported to design AIE PSs. In this study, we developed a new kind of donor that can improve the comprehensive performance of AIE PSs by expanding the π extension of aromatic rings at the end of the triphenylamine group through acene enlargement. The absorption and fluorescence peaks of anthryl-substituted AIE PS are red-shifted by 29 nm and 42 nm; the photosensitization efficiency is enhanced by 1.16 times; the AIE factor is 86.1 and the fluorescence quantum yield is 9.3%. We also demonstrated that the anthryl-based AIE PS can image and ablate cancer cells well both in vitro and in vivo. The anthryl-triphenylamine donor provides an excellent option to design donor-acceptor AIE PSs with high comprehensive performance.

Fluorination Enhances NIR-II Emission and Photothermal Conversion Efficiency of Phototheranostic Agents for Imaging-Guided Cancer Therapy.

Phototheranostics with second near-infrared (NIR-II) imaging and photothermal effect have become a burgeoning biotechnology for tumor diagnosis and precise treatment. As important parameters of phototheranostic agents (PTAs), fluorescence quantum yield (QY) and photothermal conversion efficiency (PCE) are usually considered as a pair of contradictions that is difficult to be simultaneously enhanced. Herein, a fluorination strategy for designing A-D-A type PTAs with synchronously improved QY and PCE is proposed. Experimental results show that the molar extinction coefficient (ε), NIR-II QY, and PCE of all fluorinated PTAs nanoparticles (NPs) are definitely improved compared with the chlorinated counterparts. Theoretical calculation results demonstrate that fluorination can maximize the electrostatic potential difference by virtue of the high electronegativity of fluorine, which may increase intra/intermolecular D-A interactions, tighten molecule packing, and further promote the increase of ε, ultimately leading to simultaneously enhanced QY and PCE. In these PTA NPs, FY6-NPs display NIR-II emission extended to 1400 nm with the highest NIR-II QY (4.2%) and PCE (80%). These features make FY6-NPs perform well in high-resolution imaging of vasculature and NIR-II imaging-guided photothermal therapy (PTT) of tumors. This study develops a valuable guideline for constructing NIR-II organic PTAs with high performance.

Chondroitin Sulfate Targeting Nanodrug Achieves Near-Infrared Fluorescence-Guided Chemotherapy Against Triple-Negative Breast Primary and Lung Metastatic Cancer.

Introduction: Lack of highly expressed tumor target and ligands limits application of nano-medicine against triple-negative breast cancer (TNBC). Previous study reported that placenta-derived oncofetal chondroitin sulfate glycosaminoglycan chain (CSA) expressed on 90% of stage I-III invasive ductal breast carcinomas. Our study found the CSA anchor protein VAR2CSA derived small peptide plCSA had strong binding activity with TNBC cell lines and tumor tissue. Here, we combined the AIEgens TBZ-DPNA and therapy drug paclitaxel (PTX) to fabricate near-infrared fluorescence-guided nanodrug (plCSA-NP) to investigate its targeting and anti-tumor effect on TNBC. Methods: We synthesized and purified TBZ-DPNA with one step, measured optical properties and photoluminescence (PL) spectra. We prepared nanodrug plCSA-NP by encapsulating TBZ-DPNA and PTX and conjugating them with peptide plCSA. We evaluated plCSA-NP targeting activity by examining AIEdots fluorescence signal on TNBC cell lines and subcutaneous and lung metastatic mouse model. We assessed PTX delivery effect by cytotoxicity assay on TNBC line and tumor growth of subcutaneous and lung metastatic mouse models. Results: PL spectra and TEM imaging results showed plCSA-NP had maximum emission feature at 718 nm and nearly monodispersed nanosphere with an average diameter of 70 nm. In vitro studies showed plCSA-NPs had high affinity and cytotoxicity with TNBC cell lines. In vivo subcutaneous and lung metastasis mouse studies showed plCSA-NPs accumulated on TNBC tumor tissue, and significantly prevented TNBC subcutaneous and lung metastasis tumor growth. Conclusion: In conclusion, we provide solid evidence for chondroitin sulfate targeting peptide plCSA guided nanodrug, exhibit good targeting efficiency and therapeutic effect against TNBC primary and lung metastatic tumor growth.

A Facile Structural Isomerization-Induced 3D Spatial D-A Interlocked Network for Achieving NIR-II Phototheranostic Agents.

The performances of second near-infrared (NIR-II) organic phototheranostic agents (OPTAs) depend on both molecular structure and molecular packing when used as nanoparticles (NPs). Herein, we proposed a facile structural isomerization-induced 3D spatial donor (D)-acceptor (A) interlocked network for achieving NIR-II OPTAs. Two isomers, 4MNVDPP and 6MNVDPP were synthesized and formulated into NPs. 6MNVDPP, which has a larger electrostatic potential difference, exhibits a compact 3D spatial D-A interlocked network in the crystal form, while 4MNVDPP forms 2D D-D type J-aggregates. Thus, 6MNVDPP NPs show red-shifted NIR absorption and larger molar extinction coefficient than 4MNVDPP NPs. Thanks to the typical NIR-II emission, superior photothermal-stability, high photothermal conversion efficiency (89 %) and reactive oxygen species production capacity, 6MNVDPP NPs exhibit outstanding NIR-II tiny capillary vasculature/tumor imaging ability and synergistic photothermal/photodynamic anti-cancer effect in vivo.

Dipole-Dipole and Anion-π+ Interaction Manipulation Synergistically Enhance Intrinsic Antibacterial Activities of AIEgens.

Pathogenic bacteria infections, especially multidrug resistant bacteria infections have aroused worldwide attention due to their severe threats to human beings. Thus, the development of highly effective antibacterial reagents is very important. However, the design of antimicrobials is still quite challenging for the lack of a universal design strategy. Here, a synergistic manipulation strategy of dipole-dipole and anion-π+ interaction is proposed for constructing highly efficient antimicrobials with aggregation-induced emission (AIE) feature. Firstly, four anion-π+ -type AIE luminogens were designed and synthesized. Due to the electron-donating and hydrophilic characteristic of methoxy groups, 3MOTPO containing three methoxy groups showed the largest dipole moment (5.06 Debye) and dual anion-π+ interactions in the solid state. Driven by both dipole-dipole and anion-π+ interactions, 3MOTPO showed the strongest bacterial binding ability and the best antibacterial activities (MIC90 =3.76 µM). The work offers a deep insight into the rational design of highly efficient antimicrobials for luminescence-guided antibacterial study.

A Fast-Response AIE-Active Ratiometric Fluorescent Probe for the Detection of Carboxylesterase.

Hepatocellular carcinoma (HCC) is associated with a high mortality rate worldwide. The therapeutic outcomes can be significantly improved if diagnosis and treatment are initiated earlier in the disease process. Recently, the carboxylesterase (CaE) activity/level in human plasma was reported to be a novel serological biomarker candidate for HCC. In this article, we fabricated a new fluorescent probe with AIE characteristics for the rapid detection of CaE with a more reliable ratiometric response mode. The TCFISE probe showed high sensitivity (LOD: 93.0 µU/mL) and selectivity toward CaE. Furthermore, the good pH stability, superior resistance against photobleaching, and low cytotoxicity highlight the high potential of the TCFISE probe for application in the monitoring of CaE activity in complex biological samples and in live cells, tissues, and animals.

Ratiometric imaging of butyrylcholinesterase activity in mice with nonalcoholic fatty liver using an AIE-based fluorescent probe.

Butyrylcholinesterase (BChE) is an essential human biomarker which is related to liver and neurodegenerative diseases. It is of great significance to develop a fluorescent probe that can image BChE in vitro and in vivo. Unfortunately, most fluorescent probes that are based on a single change in fluorescence intensity are susceptible to environmental interference. Therefore, we reported an easily available ratiometric fluorescent probe, TB-BChE, with aggregation-induced emission (AIE) characteristics for ratiometric imaging of BChE. TB-BChE demonstrated excellent sensitivity (LOD = 39.24 ng mL-1) and specificity for BChE. Moreover, we have successfully studied the ratiometric imaging of TB-BChE to BChE in a nonalcoholic fatty liver disease model. These results indicated that TB-BChE is expected to become a powerful analysis tool for butyrylcholinesterase research in basic medicine and clinical applications.

Metabolism and pharmacokinetics of mebendazole in Japanese pufferfish (Takifugu rubripes).

As a typical and broad-spectrum benzimidazole, mebendazole (MBZ) has long been used in human and veterinary medicine to treat parasitic infestations, and is widely employed in the aquaculture of Japanese pufferfish (Takifugu rubripes). However, there have been no studies examining the pharmacokinetic characteristics of MBZ in Japanese pufferfish. Furthermore, the presence of MBZ and its metabolites in animal-derived raw food represents a notable safety concern. Here, we investigated the metabolism of MBZ using a UPLC-Q-TOF system. Additionally, we evaluated the pharmacokinetics of MBZ and two metabolites, 2-amino-5(6)-benzoylbenzimidazole (MBZ-NH2) and 5-hydroxymebendazole (MBZ-OH), in Japanese pufferfish following intramuscular injection of 20 mg/kg MBZ. We detected three metabolites of MBZ (M1-M3), among which, 2-amino-5(6)-(a-hydroxybenzyl) benzimidazole (M3) was detected in an aquatic animal for the first time. The plasma dispositions of MBZ, MBZ-NH2, and MBZ-OH were characterized by low plasma clearance, medium distribution volume, and long terminal half-life. Moreover, these compounds were widely distributed in the muscle, from which they were rapidly cleared. The pharmacokinetics and metabolism of mebendazole in Japanese pufferfish are described for the first time in this study. Our findings provide a basis for the rational application of MBZ in Japanese pufferfish farming and contribute to our understanding of the metabolism of MBZ in cultured fish.

Acceptor Planarization and Donor Rotation: A Facile Strategy for Realizing Synergistic Cancer Phototherapy via Type I PDT and PTT.

Tumor hypoxia seriously impairs the therapeutic outcomes of type II photodynamic therapy (PDT), which is highly dependent upon tissue oxygen concentration. Herein, a facile strategy of acceptor planarization and donor rotation is proposed to design type I photosensitizers (PSs) and photothermal reagents. Acceptor planarization can not only enforce intramolecular charge transfer to redshift NIR absorption but also transfer the type of PSs from type II to type I photochemical pathways. Donor rotation optimizes photothermal conversion efficiency (PCE). Accordingly, three 3,6-divinyl-substituted diketopyrrolopyrrole (DPP) derivatives, 2TPAVDPP, TPATPEVDPP, and 2TPEVDPP, with different number of rotors were prepared. Experimental results showed that three compounds were excellent type I PSs, and the corresponding 2TPEVDPP nanoparticles (NPs) with the most rotors possessed the highest PCE. The photophysical properties of 2TPEVDPP NPs are particularly suitable for in vivo NIR fluorescence imaging-guided synergistic PDT/PTT therapy. The proposed strategy is helpful for exploiting type I phototherapeutic reagents with high efficacy for synergistic PDT and PTT.

Novel nortriterpenoids with new skeletons and limonoids from the fruits of Evodia rutaecarpa and their bioactivities.

Two novel nortriterpenoids together with 7 known compounds were isolated from the fruits of Evodia rutaecarpa. The structures of the new compounds were elucidated by spectroscopic analysis, X-ray, and electronic circular dichroism (ECD) calculations. Compound 1 is the first example of triterpenoid with a 27 (17 â†’ 12)-abeo-five-ring skeleton. In turn, compound 2 possesses a unique C/D/E linear fused ring system and a methyl on C-21. Plausible biogenetic pathway for the new compounds 1 and 2 are also proposed. Compound 1 exhibited significantly antitumor activity against A549 and LoVo cells with IC50 values of 2.0 µM and 1.9 µM, respectively. Colony formation inhibition, cell cycle arrest and cell apoptosis of compound 1 were also evaluated. Compound 2, 6, 7 and 9 showed potent neuroprotective activities against serum-deprivation induced P12 cell damage.

Highly Stable and Bright NIR-II AIE Dots for Intraoperative Identification of Ureter.

Iatrogenic ureteral injury is a dreaded complication of abdominal and pelvic surgeries, and thus, intraoperative identification of ureters is of paramount importance but lacks efficient methods and probes. Herein, we used near-infrared II (NIR-II, 1000-1700 nm) fluorescence imaging with advantages of higher spatial resolution, deeper tissue penetration, lower light scattering, and less tissue autofluorescence to identify ureters by aggregation-induced emission luminogen dots (AIE dots). The intraoperative ureteral injuries and common ureteral diseases can be visualized timely and precisely. Due to the longer emission wavelength and higher quantum yield of the AIE dots, it largely outperforms the commercial indocyanine green dye in brightness and penetration depth. It was the first time to realize the intraoperative identification of ureters in vivo using NIR-II imaging. Thus, our work provides a new platform for intraoperative monitoring during clinical operation.

Effects of electroacupuncture on patients with chronic urinary retention caused by a lower motor neuron lesion: An exploratory pilot study.

Chronic urinary retention (CUR) is defined as a non-painful bladder that remains palpable or percussible after the patient has passed urine. Acupuncture may decrease PVR and improve bladder function in patients with neurogenic CUR. The aim of this study was to preliminarily observe the effectiveness of electroacupuncture (EA) for patients with CUR caused by a lower motor neuron lesion and to provide some therapeutic data for further study.This study was a pilot study of 30 patients with CUR caused by a lower motor neuron lesion. Patients were treated with EA for 12 weeks with 36 sessions of EA.Responders were defined as participants with a decline in postvoid residual urine (PVR) volume after spontaneous urination of ≥50% from baseline. The proportion of responders, change in PVR volume from baseline after spontaneous urination, and the proportion of patients with severe difficulty with urination, who required assistance with bladder emptying and with stool retention, were measured at weeks 4, 8, and 12.Thirty patients were included in this study, and 23 completed 12 weeks of treatment. The proportion of responders at weeks 4, 8, and 12 was 6.67%, 28%, and 43.48%, respectively. Decrease in PVR volume, compared with baseline, was significant at all asessment timepoints. The proportion of patients with severe difficulty with urination, who required assistance with bladder emptying and with stool retention, decreased after treatment.EA is a potential treatment for improving bladder function in patients with CUR caused by a lower motor neuron lesion.

Enhancing the ROS generation ability of a rhodamine-decorated iridium(iii) complex by ligand regulation for endoplasmic reticulum-targeted photodynamic therapy.

The endoplasmic reticulum (ER) is a very important organelle responsible for crucial biosynthetic, sensing, and signalling functions in eukaryotic cells. In this work, we established a strategy of ligand regulation to enhance the singlet oxygen generation capacity and subcellular organelle localization ability of a rhodamine-decorated iridium(iii) complex by variation of the cyclometallating ligand. The resulting metal complex showed outstanding reactive oxygen species generation efficiency (1.6-fold higher than that of rose bengal in CH3CN) and highly specific ER localization ability, which demonstrated the promise of the metal-based photo-theranostic agent by simultaneously tuning the photochemical/physical and biological properties. Additionally, low dark cytotoxicity, high photostability and selective tumour cell uptake were featured by this complex to demonstrate it as a promising candidate in photodynamic therapy (PDT) applications. In vivo near infrared fluorescence (NIRF) imaging and tumour PDT were investigated and showed preferential accumulation at the tumour site and remarkable tumour growth suppression, respectively.

Tuning molecular aggregation to achieve highly bright AIE dots for NIR-II fluorescence imaging and NIR-I photoacoustic imaging.

Currently, bright aggregation-induced emission luminogens (AIEgens) with high photoluminescence quantum yields (PLQYs) in the NIR-II region are still limited, and thus an efficient strategy to enhance NIR-II fluorescence performance through tuning molecular aggregation is proposed here. The synthesized donor-acceptor tailored AIEgen (DTPA-TBZ) not only exhibits an excellent absorptivity in the NIR-I region, but also good fluorescence signals in the NIR-II region with an emission extending to 1200 nm. Benefiting from such improved intramolecular restriction and aggregation, a significant absolute PLQY value of 8.98% was obtained in solid DTPA-TBZ. Encouragingly, the resulting AIE dots also exhibit a high relative PLQY of up to 11.1% with IR 26 as the reference (PLQY = 0.5%). Finally, the AIE dots were applied in high performance NIR-II fluorescence imaging and NIR-I photoacoustic (PA) imaging: visualization of abdominal vessels, hind limb vasculature, and cerebral vessels with high signal to background ratios was performed via NIR-II imaging; Moreover, PA imaging has also been performed to clearly observe tumors in vivo. These results demonstrate that by finely tuning molecular aggregation in DTPA-TBZ, a good NIR-I absorptivity and a highly emissive fluorescence in the NIR-II region can be achieved simultaneously, finally resulting in a promising dual-modal imaging platform for real-world applications to achieve precise cancer diagnostics.

[Grassland vegetation phenology change and its response to climate changes in North China]. / ä¸­å›½åŒ—æ–¹è‰åœ°æ¤è¢«ç‰©å€™å˜åŒ–åŠå ¶å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Understanding phenological change of grasslands has scientific significance to reveal their responses to global climate change. Based on the data of GIMMS NDVI 3g, climate data from 1983 to 2015 and digital elevation model (DEM), dynamic threshold method was used to extract the phenological information of northern grassland [the start of growth season (SOS), the end of growth season (EOS), and the length of growth season (LOS)]. We analyzed the temporal and spatial variation of phenology of grassland vegetation and the influence of climate on LOS. The results showed that 88.9% of SOS occurred from late March to late May (90-150 d), and 68.1% of pixels were advanced with a rate of -1.5-0 d·(32 a)-1. 79.7% of EOS occurred from early October to late October (270-300 d), with a delay rate of 0-1.5 d·(32 a)-1, accounting for 70.3% of the pixel number. LOS lasted for 100-140 days and became longer (73.7%), with a rate of 0-1.5 d·(32 a)-1. LOS was significantly positively correlated with temperature (R=0.628) and weakly negatively correlated with precipitation (R=-0.091). There was a significant spatial variation. The 2000 m line above sea level was recognized as the demarcation line. LOS had a weak positive correlation with altitude under 2000 m (R=0.235) and a significant negative correlation with altitude above 2000 m (R=-0.861). Above 3000 m altitude, LOS decreased by about 10 d for every 1000 m elevation.