Synthetic progress of organic thermally activated delayed fluorescence emitters via C-H activation and functionalization.

Thermally activated delayed fluorescence (TADF) emitters have become increasingly prominent due to their promising applications across various fields, prompting a continuous demand for developing reliable synthetic methods to access them. This review aims to highlight the progress made in the last decade in synthesizing organic TADF compounds through C-H bond activation and functionalization. The review begins with a brief introduction to the basic features and design principles of TADF emitters. It then provides an overview of the advantages and concise development of C-H bond transformations in constructing TADF emitters. Subsequently, it summarizes both transition-metal-catalyzed and non-transition-metal-promoted C-H bond transformations used for the synthesis of TADF emitters. Finally, the review gives an outlook on further challenges and potential directions in this field.

Glioma stem cell-derived exosomes induce the transformation of astrocytes via the miR-3065-5p/DLG2 signaling axis.

Tumor-associated astrocytes (TAAs) in the glioblastoma microenvironment play an important role in tumor development and malignant progression initiated by glioma stem cells (GSCs). In the current study, normal human astrocytes (NHAs) were cultured and continuously treated with GSC-derived exosomes (GSC-EXOs) induction to explore the mechanism by which GSCs affect astrocyte remodeling. This study revealed that GSC-EXOs can induce the transformation of NHAs into TAAs, with relatively swollen cell bodies and multiple extended processes. In addition, high proliferation, elevated resistance to temozolomide (TMZ), and increased expression of TAA-related markers (TGF-ß, CD44, and tenascin-C) were observed in the TAAs. Furthermore, GSC-derived exosomal miR-3065-5p could be delivered to NHAs, and miR-3065-5p levels increased significantly in TAAs, as verified by miRNA expression profile sequencing and Reverse transcription polymerase chain reaction. Overexpression of miR-3065-5p also enhanced NHA proliferation, elevated resistance to TMZ, and increased the expression levels of TAA-related markers. In addition, both GSC-EXO-induced and miR-3065-5p-overexpressing NHAs promoted tumorigenesis of GSCs in vivo. Discs Large Homolog 2 (DLG2, downregulated in glioblastoma) is a direct downstream target of miR-3065-5p in TAAs, and DLG2 overexpression could partially reverse the transformation of NHAs into TAAs. Collectively, these data demonstrate that GSC-EXOs induce the transformation of NHAs into TAAs via the miR-3065-5p/DLG2 signaling axis and that TAAs can further promote the tumorigenesis of GSCs. Thus, precisely blocking the interactions between astrocytes and GSCs via exosomes may be a novel strategy to inhibit glioblastoma development, but more in-depth mechanistic studies are still needed.

Unveiling interactions of norfloxacin with microplastic in surface water by 2D FTIR correlation spectroscopy and X-ray photoelectron spectroscopy analyses.

Microplastics (MPs) has shown adsorption of hydrophilic organic matters (HOMs) in aqueous environments. However, it is still difficult to predict the adsorption behaviors of HOMs by different MPs, especially in authentic water systems. In this study, the adsorption behaviors and mechanisms of norfloxacin (NOR) onto polyamide (PA) MPs were investigated in both simulated and real surface water. The results showed that the adsorption equilibrium of NOR by PA in simulated surface water could be achieved within 15 h, while the adsorption rate of NOR in real surface was slowed down, with the equilibrium time of 25 h. Pseudo-second-order model could well describe the adsorption kinetics data. The experimental maximum adsorption capacity of NOR on PA in real surface water (e. g. 132.54 ug/g) was dramatically reduced by 37.5 % compared with that in simulated surface water (e. g. 212.25 ug/g), and the adsorption isotherm would obey Freundlich model. Besides, the leaching of NOR from the surface of PA could occur obviously at acidic environment. Furthermore, the salinity and natural organic matter exhibited significantly adverse effects on the NOR adsorption. Finally, the results of 2D Fourier transform infrared correlation spectroscopy and X-ray photoelectron spectroscopy indicated that the electrostatic, H-bond and van der Waals interactions were involved in the adsorption. More importantly, the sequential functional groups in the adsorption process followed the orders: 1638 (CO) > 1542 amide II (-NH-CO) > 717 (CH2) > 1445 (CO) > 973 amide IV (CONH). This study could provide an insight into the interactions between PA and NOR in different water environments.

Manipulating Exciton Dynamics toward Simultaneous High-Efficiency Narrowband Electroluminescence and Photon Upconversion by a Selenium-Incorporated Multiresonance Delayed Fluorescence Emitter.

Multiresonance thermal activated delayed fluorescence (MR-TADF) materials with an efficient spin-flip transition between singlet and triplet excited states remain demanding. Herein, we report an MR-TADF compound (BN-Se) simultaneously possessing efficient (reverse) intersystem crossing (ISC/RISC), fast radiative decay, close-to-unity quantum yield, and narrowband emission by embedding a single selenium atom into a common 4,4'-diazaborin framework. Benefitting from the high RISC efficiency accelerated by the heavy-atom effect, organic light-emitting diodes (OLEDs) based on BN-Se manifest excellent performance with an external quantum efficiency of up to 32.6% and an ultralow efficiency roll-off of 1.3% at 1000 cd m-2. Furthermore, the high ISC efficiency and small inherent energy loss also render BN-Se a superior photosensitizer to realize the first example of visible (λex > 450 nm)-to-UV (λem < 350 nm) triplet-triplet annihilation upconversion, with a high efficiency (21.4%) and an extremely low threshold intensity (1.3 mW cm-2). This work not only aids in designing advanced pure organic molecules with fast exciton dynamics but also highlights the value of MR-TADF compounds beyond OLED applications.

Tetracoordinate Boron-Based Multifunctional Chiral Thermally Activated Delayed Fluorescence Emitters.

Purely organic emitters have shown great potential but still suffer from low efficiency in near-infrared organic light-emitting diodes (NIR-OLEDs) due to the intensive non-radiative recombination. In this contribution, two pairs of thermally activated delayed fluorescence (TADF) enantiomers (R/S-DOBP and R/S-HDOBP) with tetracoordinate boron geometries were designed and synthesized. The TADF emitters simultaneously showed aggregation-induced emission, circularly polarized luminescence, high-contrast mechanochromism, and piezochromism behaviors. More importantly, R/S-DOBP and R/S-HDOBP revealed high photoluminescence quantum yields and efficient reverse intersystem crossing in neat films. The nondoped solution-processed OLEDs based on these unique emitters revealed the NIR emission (peaking at 716 nm) with a maximum external quantum efficiency of 1.9 % and high exciton utilization efficiency of 86 %, which represent one of the best solution-processed nondoped NIR-OLEDs.

Chiral Multi-Resonance TADF Emitters Exhibiting Narrowband Circularly Polarized Electroluminescence with an EQE of 37.2 .

Highly efficient circularly polarized luminescence (CPL) emitters with narrowband emission remain a formidable challenge for circularly polarized OLEDs (CP-OLEDs). Here, a promising strategy for developing chiral emitters concurrently featuring multi-resonance thermally activated delayed fluorescence (MR-TADF) and circularly polarized electroluminescence (CPEL) is demonstrated by the integration of molecular rigidity, central chirality and MR effect. A pair of chiral green emitters denoted as (R)-BN-MeIAc and (S)-BN-MeIAc is designed. Benefited by the rigid and quasi-planar MR-framework, the enantiomers not only display mirror-image CPL spectra, but also exhibit TADF properties with a high photoluminescence quantum yield of 96 %, a narrow FWHM of 30 nm, and a high horizontal dipole orientation of 90 % in the doped film. Consequently, the enantiomer-based CP-OLEDs achieved excellent external quantum efficiencies of 37.2 % with very low efficiency roll-off, representing the highest device efficiency of all the reported CP-OLEDs.

Meta-analysis: The efficacy of metformin and other anti-hyperglycemic agents in prolonging the survival of hepatocellular carcinoma patients with type 2 diabetes.

INTRODUCTION: This study aimed to compare the therapeutic efficacy of metformin and other anti-hyperglycemic agents in hepatocellular carcinoma (HCC) patients with type 2 diabetes (T2D). MATERIALS: A systematic electronic search on keywords including HCC and different anti-hyperglycemic agents was performed through electronic databases including Medline and EMBASE. The primary outcome was the overall survival (OS). The secondary outcomes were the recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: Six retrospective cohort studies were included for analysis: Four studies with curative treatment for HCC (618 patients with metformin and 532 patients with other anti-hyperglycemic agents) and two studies with non-curative treatment for HCC (92 patients with metformin and 57 patients with other anti-hyperglycemic agents). Treatment with metformin was associated with significantly longer OS (OR1yr=2.62, 95%CI: 1.76-3.90; OR3yr=3.14, 95%CI: 2.33-4.24; OR5yr=3.31, 95%CI: 2.39-4.59, all P<0.00001) and RFS (OR1yr=2.52, 95%CI: 1.84-3.44; OR3yr=2.87, 95%CI: 2.15-3.84; all P<0.00001; and OR5yr=2.26, 95%CI: 0.94-5.45, P=0.07) rates vs. those of other anti-hyperglycemic agents after curative therapies for HCC. However, both of the two studies reported that following non-curative HCC treatment, there were no significant differences in the OS and PFS rates between the metformin and non-metformin groups (I2>50%). CONCLUSIONS: Metformin significantly prolonged the survival of HCC patients with T2D after the curative treatment of HCC. However, the efficacy of metformin needs to be further determined after non-curative therapies for HCC patients with T2D.

Polymorph-Dependent Thermally Activated Delayed Fluorescence Emitters: Understanding TADF from a Perspective of Aggregation State.

Current research on thermally activated fluorescence (TADF) emitters is mainly based on the molecular levels, while the aggregation states of TADF emitters are to be explored deeply. Now two multifunctional emitters are reported with simultaneous TADF, aggregation induced emission (AIE), and multicolor mechanochromic luminescence (MCL) features. Both emitters also show polymorph-dependent TADF emission. Crystal structure analysis reveals that the polymorphism is ascribed to the mutable conformations in different aggregation states. This work brings new insight to TADF emitters from a perspective of aggregation states.

Identification of metabolism-associated pathways and genes involved in male and female liver cancer patients.

Hepatocellular carcinoma (HCC) is a major type of primary liver cancer. HCC is influenced by sex and multiple metabolic abnormalities. The present study aimed to compare the overall metabolic changes between male and female HCC patients and identify key metabolic genes. Metabolic genes and pathways were identified based on analyses of publicly available data. Differential expression analysis, gene set enrichment analysis, survival analysis and transcriptional regulation analysis were employed to explore sex differences and identify key metabolic genes in HCC. The results suggested that female patients had more severe metabolic gene expression abnormalities and pathway deregulation than male patients. This study identified 9 key metabolic genes, and only upregulated ALDH1A2 independently increased overall survival risk in patients. Bioinformatic analyses suggest that upregulated GATA3 and TAL1 activate ALDH1A2 and then disrupt amino acid and carbohydrate metabolism, which may increase the risk of HCC. This study identified a novel contribution of upregulated ALDH1A2 to HCC. Future studies are needed to elucidate the potential metabolic mechanism of the role of ALDH1A2 in HCC.

A Simple Organic Molecule Realizing Simultaneous TADF, RTP, AIE, and Mechanoluminescence: Understanding the Mechanism Behind the Multifunctional Emitter.

Aggregation-induced emission (AIE), thermally activated delayed fluorescence (TADF), room-temperature phosphorescence (RTP), and mechanoluminescence (ML) have attracted widespread interest. However, a multifunctional organic emitter exhibiting simultaneous AIE, TADF, RTP, and ML has not been reported. Now, two multifunctional blue emitters with very simple structures, mono-DMACDPS and Me-DMACDPS, exhibit typical AIE, TADF, and RTP properties but different behavior in mechanoluminescence. Crystal structure analysis reveals that large dipole moment and multiple intermolecular interactions with tight packing mode endow mono-DMACDPS with strong ML. Combined with the data of crystal analysis and theoretical calculation, the separated monomer and dimer in the crystal lead to the typical TADF and RTP properties, respectively. Simple-structure mono-DMACDPS is the first example realizing TADF, RTP, AIE, and ML simultaneously.

Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity.

Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro. Scutellarin treatment significantly reduced STAT3 and Girders of actin filaments (Girdin) expression, STAT3 and Akt phosphorylation in HCC cells. Introduction of STAT3 overexpression restored the scutellarin-downregulated Girdin expression, Akt activation, migration and invasion of HCC cells. Furthermore, induction of Girdin overexpression completely abrogated the inhibition of scutellarin on the Akt phosphorylation, migration and invasion of HCC cells. Scutellarin can inhibit HCC cell metastasis in vivo, and migration and invasion in vitro by down-regulating the STAT3/Girdin/Akt signaling.

Efficient approach to 2-hydroxy-2,3-dihydrofuran derivatives and its application for the synthesis of novel 4-(1H-pyrazol-4-yl)pyridazines.

A highly efficient method for the synthesis of 2-hydroxy-2,3-dihydrofuran derivatives from 1,4-enediones and phenacyl pyridinium halides via a domino reaction has been developed. This is a simple and beneficial strategy for the construction of 2-hydroxy-2,3-dihydrofuran compounds from readily available starting materials under mild conditions. Moreover, the application of this reaction provides a straightforward and practical route for the synthesis of the novel 4-(1H-pyrazol-4-yl)pyridazine skeleton.

Copper-catalyzed domino synthesis of 2-imino-1H-imidazol-5(2H)-ones and quinoxalines involving C-C bond cleavage with a 1,3-dicarbonyl unit as a leaving group.

Although 2-imino-1H-imidazol-5(2H)-ones have important biological activities in metabolism, their synthesis has rarely been investigated. Quinoxalines as "privileged scaffolds" in medicinal chemistry have been extensively investigated, but the development of novel and efficient synthetic methods remains very attractive. Herein, we have developed two copper-catalyzed domino reactions for the synthesis of 2-imino-1H-imidazol-5(2H)-ones and quinoxalines involving CC bond-cleavage with a 1,3-dicarbonyl unit as a leaving group. The domino sequence for the synthesis of 2-imino-1H-imidazol-5(2H)-ones includes aza-Michael addition, intramolecular cyclization, CC bond-cleavage, 1,2-rearrangement, and aerobic dehydrogenation reaction, whereas the domino sequence for the synthesis of quinoxalines includes aza-Michael addition, intramolecular cyclization, elimination reaction, and CC bond-cleavage reaction. The two domino reactions have significant advantages including high efficiency, mild reaction conditions, and high tolerance of various functional groups.

Brønsted acid promoted addition-cyclization and C-C bond cleavage: a convenient synthesis of 2-amino-5-aroylmethylthiazoles derivatives.

A Brønsted acid promoted C-C bond cleavage method for the synthesis of novel 2-amino-5-aroylmethylthiazole derivatives has been directly developed from 1,4-enediones and thioureas through self-sequenced thio-Michael-addition, intramolecular selective cyclization, dehydration/aromatization, and C-C bond cleavage reactions. It is noteworthy that this reaction has significant advantages in simple reagents, under environmentally benign conditions and with excellent yields. This highly efficient method is also a highly attractive alternative for the preparation of PLTP, CETP inhibitors and novel biheterocycles.

Synthesis of tetrasubstituted unsymmetrical 1,4-enediones via copper-promoted autotandem catalysis and air as the oxidant.

An efficient procedure has been developed for the preparation of tetrasubstituted unsymmetrical 1,4-enediones via copper-promoted autotandem catalysis and air as the oxidant. Various N-nucleophiles are compatible with this reaction, such as morpholine, piperidine, pyrrolidine, arylamines, pyrazole, imidazole, benzimidazole, and benzotriazole. This reaction also has significant advantages in easily available substrates, atom economy, bond-forming efficiency, and environmental benignity.

Versatile Host Materials for Both D-A-Type and Multi-Resonance TADF Emitters toward Solution-Processed OLEDs with Nearly 30% EQE.

Fabricating solution-processible host material for thermally activated delayed fluorescence (TADF) emitter remains a formidable challenge for organic light-emitting diodes (OLEDs). In this work, two new host materials, namely 3CzAcPy and 9CzAcPy, are found to exhibit high triplet energy levels, high thermal stability, and excellent film morphology from a solution process. An in-depth analysis on the photophysical data and device performance reveals the isomeric effect of the host materials has a significant impact not only on the host properties, but also on the host-dopant interactions and thus the performance of the resulting solution-processed TADF OLEDs. Impressively, the new hosts are proven to be suitable for both donor-acceptor type and multi-resonance TADF emitters, achieving state-of-the-art device performance. By using the new host 9CzAcPy, solution-processed OLED based on a donor-acceptor TADF emitter of DPAC-PCN, a maximum external quantum efficiency (EQE) of 29.5% is achieved, and solution-processed narrowband OLED based on a multiple-resonance TADF emitter of BN-CP1 acquires a maximum EQE of 26.6%. These efficiencies represent the highest values among the solution-processed TADF OLEDs. This study highlights the significance of host-dopant interactions in modulating the electroluminescence performance of TADF emitters, and provides an effective design principle for solution-processible host materials.

A novel antibody-TCR (AbTCR) T-cell therapy is safe and effective against CD19-positive relapsed/refractory B-cell lymphoma.

PURPOSE: A barrier to widespread adoption of chimeric antigen receptor (CAR) T-cell therapy is toxicity. To address this, we recently developed a novel antibody-T-cell receptor (AbTCR) platform (trademarked as ARTEMIS®) which was designed to leverage natural immune receptor signaling and regulation. The AbTCR platform includes a gamma/delta (γδ) TCR-based AbTCR construct and a separate co-stimulatory molecule, both engineered to be tumor-specific. Here, we aim to assess the safety and preliminary efficacy of a CD19-directed AbTCR T-cell therapy. METHODS: We generated ET019003 T cells, which are autologous CD19-directed AbTCR T cells. We then conducted an early phase I study to evaluate the safety and preliminary efficacy of ET019003 T cells for the treatment of CD19-positive relapsed/refractory (r/r) B-cell lymphoma. RESULTS: Sixteen patients enrolled in this study and 12 patients were treated. Of the 12 patients treated, 6 patients (50%) achieved a complete response (CR), and 4 (33%) achieved a partial response (PR) (best objective response rate [ORR] of 83%). CRs were durable, including 2 patients with ongoing CRs for 22.7 months and 23.2 months. ET019003 was well-tolerated with an attractive safety profile. No patients experienced severe (grade ≥ 3) cytokine release syndrome (CRS) and only 1 patient experienced immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade. Significant elevations of cytokine levels were not seen, even in patients with marked expansion of ET019003 T cells. CONCLUSION: This study provides initial clinical validation of the AbTCR platform as a novel cancer treatment with the potential to provide durable clinical benefit with low toxicity. TRIAL REGISTRATION: NCT03642496; Date of registration: August 22, 2018.

Quantitative assessment of interactions of hydrophilic organic contaminants with microplastics in natural water environment.

The interaction between microplastics (MPs) and hydrophilic organic contaminants (HOCs) in natural water environment has recently raised great public attentions due to the potential toxicity to humans. However, the quantitative assessment is less studied. In this study, the interaction between ciprofloxacin (CIP) and ofloxacin (OFL) (two important HOCs) and virgin and aged polystyrene (PS) was investigated. The aged PS showed higher adsorption rate and capacity than the virgin PS, due to its larger surface area and more O-containing groups. The pH-dependent adsorption of CIP was higher than OFL on both virgin and aged PS; the maximum adsorption for both HOCs occurred at pH 5. The sequential orders of functional groups for the adsorption were discovered according to the study by the 2D correlation Fourier transform infrared spectroscopy. Several mechanisms existed for the interaction: (1) at 3.0 < pH < 5.0, the electrostatic attraction (EA) was inhibited while H-bond (HB) was dominant, accounting for > 60% of the total uptake; (2) at 5.0 < pH < 8.0, the contribution of EA increased to around 50-60% while HB decreased to 30-40%; (3) at 8.0 < pH < 10.0, EA, HB and π-π conjugation caused 30-40%, 25-40% and 20-45% of the total uptake, respectively; (4) at 10.0 < pH < 12.0, π-π conjugation accounted for 90-100%. Notably, higher adsorption of CIP was mainly attributed to the presence of secondary amino groups and its higher pKa value, correspondingly leading to the additional ordinary HB and negative charge-assisted HB, and EA interactions with PS. This study further provides clear evidences on the risk of MPs and HOCs on humans and aqueous living organisms.

Bipolar Hemicyanine-Based Photodynamic Modulation of Type I Pathway for Efficient Sterilization and Real-Time Monitoring.

The development of photosensitizers with low oxygen dependence for generating type I ROS is in high demand to be able to treat pathogenic infections in hypoxic conditions. Here, we report a series of cationic bipolar hemicyanines (C3, C6, and C10) with alkyl linkers of varying lengths that are found to exclusively produce hydroxyl radicals and superoxide radicals with the aid of white light and that have different antibacterial abilities toward a variety of pathogens. Furthermore, hemicyanines could differentiate live from dead bacteria to track the status of pathogens in real time. It is expected that hemicyanines could be applied for combatting various microbial infections in hypoxia and real-time tracking.

Optically Programmable Circularly Polarized Photodetector.

The detection of circularly polarized light (CPL) has aroused wide attention from both the scientific and industrial communities. However, from the optical activity of the chiral layer in the conventional CPL photodetectors, the sign inversion property is difficult to be achieved. As a result, great challenges arise during the preparation of miniaturized and integrated devices for tunable CPL detection applications. Along these lines, in this work, by taking advantage of the CPL-induced chirality characteristics of the achiral poly(9,9-di-n-hexylfluorene-alt-benzothiadiazole) (F6BT) and the good crystalline and electrical properties of the poly(3-hexylthiophene) (P3HT) film, an optically programmable CPL photodetector was fabricated. Interestingly, the device exhibited excellent discrimination between left- and right-handed CPL, while the maximum anisotropy factor of responsivity was 0.425. On top of that, the rigorously controlled chirality of the F6BT and the capability to be switched by the handedness of CPL was leveraged to realize the switchable detection of both L-CPL and R-CPL. Furthermore, a CPL photodetector array was fabricated, and the image processing and cryptographic characteristics were demonstrated. The proposed device configuration can find application in various scientific fields, including photonics, emission, conversion, or sensing with CPL but also is anticipated to play a key role for imaging and anticounterfeiting applications.