A novel molecular model of connecting electron‐donating (D) and electron‐withdrawing (A) moieties via a space‐enough and conjugation‐forbidden linkage (D‐Spacer‐A) is proposed to develop efficient ...non‐doped thermally activated delayed fluorescence (TADF) emitters. 10‐(4‐(4‐(4,6‐diphenyl‐1,3,5‐triazin‐2‐yl) phenoxy) phenyl)‐9,9‐dimethyl‐9,10‐dihydroacridine (DMAC‐o‐TRZ) was designed and synthesized accordingly. As expected, it exhibits local excited properties in single‐molecule state as D‐Spacer‐A molecular backbone strongly suppress the intramolecular charge‐transfer (CT) transition. And intermolecular CT transition acted as the vital radiation channel for neat DMAC‐o‐TRZ film. As in return, the non‐doped device exhibits a remarkable maximum external quantum efficiency (EQE) of 14.7 %. These results prove the feasibility of D‐Spacer‐A molecules to develop intermolecular CT transition TADF emitters for efficient non‐doped OLEDs.
Non‐doped OLEDs: A novel molecular model of connecting electron‐donating (D) and electron‐withdrawing (A) moieties through a conjugation‐forbidden spacer is proposed to develop efficient thermally activated delayed fluorescence emitters for non‐doped organic light‐emitting diodes. The structure shows intermolecular charge‐transfer (CT) transitions as the major radiative channel and a suppressed effect of photoluminescence concentration quenching.
Recurrence and metastasis are the leading causes of tumour-related death in patients with oesophageal squamous cell carcinoma (ESCC). Tumour-infiltrating natural killer cells (NK cells) display ...powerful cytotoxicity to tumour cells and play a pivotal role in tumour therapy. However, the phenotype and functional regulation of NK cells in oesophageal squamous cell carcinoma (ESCC) remains largely unknown.
Single cell suspensions from blood and tissue samples were isolated by physical dissociation and filtering through a 70 μm cell strainer. Flow cytometry was applied to profile the activity and function of NK cells, and an antibody chip experiment was used to identify and quantitate cytokine levels. We studied IL-6 and IL-8 function in primary oesophageal squamous carcinoma and NK cell co-cultures in vitro and by a xenograft tumour model in vivo. Western blotting was used to quantitate STAT3 (signal transducer and activator of transcription 3) and p-STAT3 levels. Finally, we performed an IHC array to analyse IL-6/IL-8 (interleukin 6/interleukin 8) expression in 103 pairs of tumours and matched adjacent tissues of patients with ESCC to elucidate the correlation between IL-6 or IL-8 and clinical characteristics.
The percentages of NK cells in both peripheral blood and tumour tissues from patients with ESCC were significantly increased in comparison with those in the controls and correlated with the clinical characteristics. Furthermore, the decrease in activating receptors and increase in inhibitory receptors on the surface of tumour-infiltrating NK cells was confirmed by flow cytometry. The level of granzyme B, the effector molecule of tumour-infiltrating NK cells, was also decreased. Mechanistically, primary ESCC cells activated the STAT3 signalling pathway on NK cells through IL-6 and IL-8 secretion, leading to the downregulation of activating receptors (NKp30 and NKG2D) on the surface of NK cells. An ex vivo study showed that blockade of STAT3 attenuated the IL-6/IL-8-mediated impairment of NK cell function. Moreover, the expression of IL-6 or IL-8 in tumour tissues was validated by immunohistochemistry to be positively correlated with tumour progression and poor survival, respectively.
Tumour cell-secreted IL-6 and IL-8 impair the activity and function of NK cells via STAT3 signalling and contribute to oesophageal squamous cell carcinoma malignancy.
The conformational distribution and mutual interconversion of thermally activated delayed fluorescence (TADF) emitters significantly affect the exciton utilization. However, their influence on the ...photophysics in amorphous film states is still not known due to the lack of a suitable quantitative analysis method. Herein, we used temperature‐dependent time‐resolved photoluminescence spectroscopy to quantitatively measure the relative populations of the conformations of a TADF emitter for the first time. We further propose a new concept of “self‐doping” for realizing high‐efficiency nondoped OLEDs. Interestingly, this “compositionally” pure film actually behaves as a film with a dopant (quasi‐equatorial form) in a matrix (quasi‐axial form). The concentration‐induced quenching that may occur at high concentrations is thus expected to be effectively relieved. The “self‐doping” OLED prepared with the newly developed TADF emitter TP2P‐PXZ as a neat emitting layer realizes a high maximum external quantum efficiency of 25.4 % and neglectable efficiency roll‐off.
Until now, the influence of the conformational distribution on the photophysics and device performance of thermally activated delayed fluorescence (TADF) emitters has not been clear. Herein, conformational populations in disordered solid states are quantitatively measured for the first time. A high‐performance “self‐doping” OLED with a maximum external quantum efficiency of 25.4 % is achieved.
As an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its ...potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored.
The expression of KDM6B in human ESCC tissues and cell lines was examined using RT-qPCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC.
We show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPβ, leading to the promotion of C/EBPβ transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells.
The present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPβ depending on its H3K27 demethylase activity.
Mesenchymal stromal cell‐derived extracellular vesicles (MSC‐EVs) turn out to be a promising source of cell‐free therapy. Here, we investigated the biodistribution and effect of nebulized human ...adipose‐derived MSC‐EVs (haMSC‐EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC‐EVs in healthy volunteers. DiR‐labelled haMSC‐EVs were used to explore the distribution of nebulized haMSC‐EVs in the murine model. Pseudomonas aeruginosa‐induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL‐6, TNF‐α and IL‐10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC‐EVs through the nebulized route. Twenty‐four healthy volunteers were involved and received the haMSC‐EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, NCT04313647). Nebulizing haMSC‐EVs improved survival rate to 80% at 96 h in P. aeruginosa‐induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC‐EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC‐EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC‐EVs in lung injury diseases.
Two novel thermally activated delayed fluorescence (TADF) emitters, 3-phenylquinolino3,2,1-deacridine-5,9-dione (3-PhQAD) and 7-phenylquinolino3,2,1-deacridine-5,9-dione (7-PhQAD), were designed ...and synthesized based on a rigid quinolino3,2,1-deacridine-5,9-dione (QAD) framework. With the effective superimposed resonance effect from electron-deficient carbonyls and electron-rich nitrogen atom, both emitters realize significant TADF characteristics with small ΔE STs of 0.18 and 0.19 eV, respectively. And, molecular relaxations were dramatically suppressed for both emitters because of their conjugated structure. In the devices, 3-PhQAD realizes superior performance with a maximum external quantum efficiency (EQE) of 19.1% and a narrow full width at half-maximum (FWHM) of 44 nm, whereas a maximum EQE of 18.7% and an extremely narrow FWHM of 34 nm are realized for 7-PhQAD. These superior results reveal that apart from nitrogen and boron-aromatic systems, QAD framework can also act as a TADF matrix with effective resonance effect, and QAD derivatives are ideal candidates to develop TADF emitters with narrow FWHMs for practical applications.
A bacterium, designated strain ZK17L-C2
, was isolated from the leaf tissues of wheat (
) collected in Chengdu, Sichuan Province, PR China. It is aerobic, non-motile, Gram-negative, rod-shaped and ...red-to-pink in colour. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZK17L-C2
belonged to the genus
and was most closely related to
KCTC 12533
(98.68 %) and
9PBR-2
(98.19 %). Digital DNA-DNA hybridization (dDDH) values between strain ZK17L-C2
and these two type strains were 26.6 and 26.5 %, and average nucleotide identity (ANI) values were 84.9 and 84.8 %, respectively; these values are lower than the proposed and generally accepted species boundaries for dDDH and ANI. The genomic DNA G+C content of strain ZK17L-C2
was 59.4 mol%. It can grow at pH 5.5-7.5 and 15-30 °C, which is different from the closely related type strains. The major fatty acids of strain ZK17L-C2
were iso-C
, C
and C
. Overall, the results from biochemical, chemical taxonomy and phylogenetic analyses indicate that strain ZK17L-C2
(=CGMCC 1.19373
=KCTC 92184
) represents a new species of the genus
, for which the name
sp. nov. is proposed.
Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease and characterized by slow and progressive loss of dopamine (DA) neurons in the midbrain ...substantia nigra. Microglia-mediated neuroinflammation has been considered as the major central event in the process of DA neuronal loss. Thus, inhibition of neuroinflammation could possess a more viable strategy for PD treatment. Naringenin (NAR), a natural flavanoid contained in citrus fruit and grapefruits, possesses amounts of pharmacological activities. Recent studies indicated that NAR produced neuroprotection against several neurological disorders. However, the mechanisms underlying NAR-generated neuroprotection are not fully illuminated.
In the present study, rat nigral stereotaxic injection of lipopolysaccharide (LPS)-induced DA neuronal loss was performed to investigate NAR-mediated neuroprotection. In addition, BV-2 and MN9D cell lines were applied to explore the underlying mechanisms.
NAR protected DA neurons against LPS-induced neurotoxicity. Also, NAR suppressed microglial nod-like receptor protein 3 (NLRP3) inflammasome signaling activation and the subsequent pro-inflammatory factors release. In addition, NAR-mediated DA neuroprotection was dependent on the inhibition of microglial NLRP3 inflammasome activation, as evidenced by the observations that NAR-reduced pro-inflammatory factors production and further NAR-exerted DA neuroprotection against LPS-induced neuronal damage was not discerned after microglial NLRP3 siRNA treatment.
This study demonstrated that NAR targeted microglial NLRP3 inflammasome to protect DA neurons against LPS-induced neurotoxicity. These findings suggest NAR might hold a promising therapeutic potential for PD.
Two unusual polyketide-sesquiterpene metabolites, craterodoratins T (
) and U (
), along with the known compound craterellin A (
), were isolated from the higher fungus
. The structures of isolated ...compounds were characterized based on nuclear magnetic resonance (NMR) and mass spectrum (MS) spectroscopic analysis, while the absolute configuration of the compounds was determined by theoretical NMR and electronic circular dichroism (ECD) calculations. Compound
possessed a rare structure with two aromatic groups. Compounds
and
showed immunosuppressive activity with IC
values ranging from 5.516 to 19.953
M.
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