Low efficiency roll-off phosphorescent organic light-emitting devices using thermally activated delayed fluorescence hosts materials based 1, 2, 4-triazole acceptor

The host in phosphrescent organic light emitting devices (PhOLEDs), showing the thermally activated delayed fluorescence (TADF) charateristic, can effectively overcome the efficiency roll-off. Herein, six bipolar compounds with donor-π-acceptor (D-π-A) and D-π-A-π-D structures have been synthesized using 1,2,4-triazole derivative (TAZ) as an acceptor and phenothiazine (PTZ), phenoxazine (PXZ), and 9, 9-dimethylacridane (DMAC) as donors. The molecular structures were confirmed by 1H NMR, 13C NMR and X-ray single-crystal diffractions. The large steric hindrance endows these molecules with typical TADF features, including the small singlet-triplet energy splitting (Delta E-ST) of 0.08–0.30 eV and completely spatially separate highest occupied molecular orbitals (HOMO) and the lowest unoccupied molecular orbitals (LUMO) electron densities. The PhOLEDs hosted by these novel TADF materials display excellent performances with low efficiency roll-off

Establishment and phenotype verification of mouse oviductal epithelial organoids

Objective·To establish a culture system of oviductal epithelial organoids from wild type (WT) mice and miR-34b/c-/- and miR-449-/- double knockout (dKO) mice, and verify the phenotypes.Methods·The oviduct epithelial cells of WT mice and dKO mice were isolated and purified by enzyme digestion and differential adhesion method, and the purity of the isolated oviduct epithelial cells was identified by immunofluorescence staining. The numbers, growth rates and sizes of oviductal epithelial organoids between WT mice and dKO mice were compared by counting and diameter measurement. Hematoxylin-eosin (H-E) staining and transmission electron microscope (TEM) were used to observe the morphology and structure of the oviductal epithelial organoids. The proportions of ciliated cells and secretory cells in the oviductal epithelial organoids from WT mice and dKO mice were observed and counted by immunofluorescence staining. Immunohistochemistry (IHC), real-time quantitative PCR (RT-qPCR) and Western blotting were used to observe the expression levels of marker genes of ciliated cells and secretory cells in the oviductal epithelial organoids.Results·The purity of the isolated and purified oviduct epithelial cells was high. Compared with the organoids from WT mice, the oviductal epithelial organoids from dKO mice grew faster and larger, and were more in number. But they developed more slowly than those from WT mice, as the invaginations of the dKO mice organoids appeared on the 28th day of culture, while the WT mice organoids exhibited the same structures on the 16th day. The oviductal epithelial organoids showed similar structures as those of the oviduct in vivo under hematoxylin-eosin (H-E) staining and TEM. Immunofluorescence staining showed that the ciliated cells of oviductal epithelial organoids from dKO mice were significantly reduced and the secretory cells were significantly increased (both P<0.05). IHC showed that the molecular expression patterns of the oviductal epithelial organoids were consistent with those of the oviducts in vivo, i.e. the expression levels of ciliated cell markers acetylated α-tubulin (Ac-α-tubulin) and forkhead box J1 (FOXJ1) decreased, and the expression level of the secretory cell marker paired box 8 (PAX8) increased. RT-qPCR showed that the mRNA levels of Foxj1 and tubulin β class Ⅳa (Tubb4a) decreased (both P<0.05), while Pax8 increased in the oviductal epithelial organoids of dKO mice (P<0.05). Western blotting results showed that the protein expression level of FOXJ1 in the organoids of dKO mice significantly decreased, while the expression of PAX8 significantly increased (both P<0.05).Conclusion·The culture system of oviductal epithelial organoids of WT mice and dKO mice are successfully constructed, which can simulate the phenotypes of mouse oviduct in vivo

Apoptosis signal-regulating kinase 1 (Ask1) deficiency alleviates MPP+-induced impairment of evoked dopamine release in the mouse hippocampus

The dopaminergic system is susceptible to dysfunction in numerous neurological diseases, including Parkinson’s disease (PD). In addition to motor symptoms, some PD patients may experience non-motor symptoms, including cognitive and memory deficits. A possible explanation for their manifestation is a disturbed pattern of dopamine release in brain regions involved in learning and memory, such as the hippocampus. Therefore, investigating neuropathological alterations in dopamine release prior to neurodegeneration is imperative. This study aimed to characterize evoked hippocampal dopamine release and assess the impact of the neurotoxin MPP+ using a genetically encoded dopamine sensor and gene expression analysis. Additionally, considering the potential neuroprotective attributes demonstrated by apoptosis signal-regulating kinase 1 (Ask1) in various animal-disease-like models, the study also aimed to determine whether Ask1 knockdown restores MPP+-altered dopamine release in acute hippocampal slices. We applied variations of low- and high-frequency stimulation to evoke dopamine release within different hippocampal regions and discovered that acute application of MPP+ reduced the amount of dopamine released and hindered the recovery of dopamine release after repeated stimulation. In addition, we observed that Ask1 deficiency attenuated the detrimental effects of MPP+ on the recovery of dopamine release after repeated stimulation. RNA sequencing analysis indicated that genes associated with the synaptic pathways are involved in response to MPP+ exposure. Notably, Ask1 deficiency was found to downregulate the expression of Slc5a7, a gene encoding a sodium-dependent high-affinity choline transporter that regulates acetylcholine levels. Respective follow-up experiments indicated that Slc5a7 plays a role in Ask1 deficiency-mediated protection against MPP+ neurotoxicity. In addition, increasing acetylcholine levels using an acetylcholinesterase inhibitor could exacerbate the toxicity of MPP+. In conclusion, our data imply that the modulation of the dopamine-acetylcholine balance may be a crucial mechanism of action underlying the neuroprotective effects of Ask1 deficiency in PD

A Lactate Fermentation Mutant of Toxoplasma Stimulates Protective Immunity Against Acute and Chronic Toxoplasmosis

Toxoplasma gondii is an important zoonotic pathogen infecting one-third of the world’s population and numerous animals, causing significant healthcare burden and socioeconomic problems. Vaccination is an efficient way to reduce global sero-prevalence, however, ideal vaccines are not yet available. We recently discovered that the Toxoplasma mutant lacking both lactate dehydrogenases LDH1 and LDH2 (Δldh) grew well in vitro but was unable to propagate in mice, making it a good live vaccine candidate. Here, we tested the protection efficacy of ME49 Δldh using a mouse model. Vaccinated mice were efficiently protected from the lethal challenge of a variety of wild-type strains, including type 1 strain RH, type 2 strain ME49, type 3 strain VEG, and a field isolate of Chinese 1. The protection efficacies of a single vaccination were nearly 100% for most cases and it worked well against the challenges of both tachyzoites and tissue cysts. Re-challenging parasites were unable to propagate in vaccinated mice, nor did they make tissue cysts. High levels of Toxoplasma-specific IgG were produced 30 days after immunization and stayed high during the whole tests (at least 125 days). However, passive immunization of naïve mice with sera from vaccinated mice did reduce parasite propagation, but the overall protection against parasite infections was rather limited. On the other hand, Δldh immunization evoked elevated levels of Th1 cytokines like INF-γ and IL-12, at early time points. In addition, splenocytes extracted from immunized mice were able to induce quick and robust INF-γ and other pro-inflammatory cytokine production upon T. gondii antigen stimulation. Together these results suggest that cellular immune responses are the main contributors to the protective immunity elicited by Δldh vaccination, and humoral immunity also contributes partially. We also generated uracil auxotrophic mutants in ME49 and compared their immune protection efficiencies to the Δldh mutants. The results showed that these two types of mutants have similar properties as live vaccine candidates. Taken together, these results suggest that mutants lacking LDH were severely attenuated in virulence but were able to induce strong anti-toxoplasma immune responses, therefore are good candidates for live vaccines

Novel blue fluorescent emitters structured by linking triphenylamine and anthracene derivatives for organic light-emitting devices with EQE exceeding 5%

Achieving an external quantum efficiency exceeding 5% for traditional blue fluorescent organic light emitting devices (OLEDs) is still a current challenge due to the 25% limit of the radiative exciton yield. Bipolar organic molecules with a special hybrid local-excited and charge-transfer state have showed huge potential to address this issue. Herein, we designed and synthesized two novel bipolar compounds, namely TPA-AN-NA and TPA-AN-TFP, which were structured by simply linking a donor of triphenylamine (TPA) and both acceptors of anthracene derivatives. Both resulting compounds show good blue emission with emission peaks at 468 and 471 nm and photoluminescence quantum yields of 30.68 and 23.96% in thin films for TPA-AN-NA and TPA-AN-TFP, respectively. They also exhibit good solubility and can dissolve in several organic solvents with different polarities. Further, the fabricated blue OLEDs with TPA-AN-NA and TPA-AN-TFP as emitters also realize the corresponding blue emission well with electroluminescence peaks at 464 and 472 nm, respectively. The TPA-AN-NA-based blue device achieves a high external quantum efficiency of 5.44% and a radiative exciton yield of 56.68%, exceeding the theoretical limit

Two novel bipolar hosts based on 1,2,4-triazole derivatives for highly efficient red phosphorescent OLEDs showing a small efficiency roll-off

Achieving high efficiency and small efficiency roll-off simultaneously for red phosphorescent organic light-emitting diodes (PhOLEDs) is still a challenge, which is largely related to the host material used in device fabrication. In this wok, we designed and synthesized two novel bipolar host materials, termed 2Cz-TAZ-2Cz and 3Cz-TAZ-3Cz in which 1,2,4-triazole was introduced at the C-2 and C-3 positions of 9-phenylcarbazole, respectively. The materials\u27 photophysical properties were studied in detail.. It was found that 2Cz-TAZ-2Cz and 3Cz-TAZ-3Cz possess excellent thermal stability with thermal decomposition temperature (Td) of 457 and 432 °C, respectively, and that 2Cz-TAZ-2Cz has a better bipolar carrier transport compared to the typical host 4, 4′-bis(9H-carbazole-9-yl)-biphenyl (CBP). Based on the excellent performance of these materials, red phosphorescent OLEDs with 2Cz-TAZ-2Cz and 3Cz-TAZ-3Cz as hosts and bis(1-phenylisoquinoline)(acetylacetonate)iridium (III) (Ir(piq)2acac) as emitter were fabricated. The optimized 2Cz-TAZ-2Cz-based device achieved a high maximum current efficiency and external quantum efficiency (EQE) of 12.4 cd/A and 16.60%, respectively. Moreover, this device also exhibits a small efficiency roll-off, i.e., the EQE is lowered by only 12.0% and 29.4% at a brightness of 1000 cd/m2 and 10,000 cd/m2, respectively, which is superior to CBP-based device, indicating a potential far-reaching application

Global intron retention mediated gene regulation during CD4+ T cell activation.

T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Using strand-specific RNA-seq, we observed that intron retention is prevalent in polyadenylated transcripts in resting CD4(+) T cells and is significantly reduced upon T cell activation. Several lines of evidence suggest that intron-retained transcripts are less stable than fully spliced transcripts. Strikingly, the decrease in intron retention (IR) levels correlate with the increase in steady-state mRNA levels. Further, the majority of the genes upregulated in activated T cells are accompanied by a significant reduction in IR. Of these 1583 genes, 185 genes are predominantly regulated at the IR level, and highly enriched in the proteasome pathway, which is essential for proper T cell proliferation and cytokine release. These observations were corroborated in both human and mouse CD4(+) T cells. Our study revealed a novel post-transcriptional regulatory mechanism that may potentially contribute to coordinated and/or quick cellular responses to extracellular stimuli such as an acute infection

A comprehensive review of Tripterygium wilfordii hook. f. in the treatment of rheumatic and autoimmune diseases: Bioactive compounds, mechanisms of action, and future directions

Rheumatic and autoimmune diseases are a group of immune system-related disorders wherein the immune system mistakenly attacks and damages the body’s tissues and organs. This excessive immune response leads to inflammation, tissue damage, and functional impairment. Therapeutic approaches typically involve medications that regulate immune responses, reduce inflammation, alleviate symptoms, and target specific damaged organs. Tripterygium wilfordii Hook. f., a traditional Chinese medicinal plant, has been widely studied in recent years for its application in the treatment of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Numerous studies have shown that preparations of Tripterygium wilfordii have anti-inflammatory, immunomodulatory, and immunosuppressive effects, which effectively improve the symptoms and quality of life of patients with autoimmune diseases, whereas the active metabolites of T. wilfordii have been demonstrated to inhibit immune cell activation, regulate the production of inflammatory factors, and modulate the immune system. However, although these effects contribute to reductions in inflammatory responses and the suppression of autoimmune reactions, as well as minimize tissue and organ damage, the underlying mechanisms of action require further investigation. Moreover, despite the efficacy of T. wilfordii in the treatment of autoimmune diseases, its toxicity and side effects, including its potential hepatotoxicity and nephrotoxicity, warrant a thorough assessment. Furthermore, to maximize the therapeutic benefits of this plant in the treatment of autoimmune diseases and enable more patients to utilize these benefits, efforts should be made to strengthen the regulation and standardized use of T. wilfordii

Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis

ObjectivesHTR2A is previously identified as a susceptibility gene for rheumatoid arthritis (RA). In this study, we performed the association analysis between DNA methylation of HTR2A with RA within peripheral blood samples.MethodsWe enrolled peripheral blood samples from 235 patients with RA, 30 osteoarthritis (OA) patients, and 30 healthy controls. The DNA methylation levels of about 218 bp from chr13: 46898190 to chr13: 46897973 (GRCh38/hg38) around HTR2A cg15692052 from patients were analyzed by targeted methylation sequencing.ResultsWe measured methylation status for 7 CpGs in the promoter region of HTR2A and obseved overall methylation status are signficantly increased in RA compared with normal inviduals (FDR= 9.05 x 10-5). The average cg15692052 methylation levels (methylation score) showed a positive correlation with CRP (r=0.15, P=0.023). Compared with the OA group or HC group, the proportion of haplotypes CCCCCCC (FDR=0.02 and 2.81 x 10-6) is signficantly increased while TTTTTCC (FDR =0.01) and TTTTTTT(FDR =6.92 x 10-3) are significantly decreased in RA. We find methylation haplotypes combining with RF and CCP could signficantly enhance the performance of the diagnosing RA and its comorbidities (hypertension, interstitial lung disease, and osteoporosis), especially in interstitial lung disease.ConclusionsIn our study, we found signficant hypermethylation of promoter region of HTR2A which indicates the potential clinical diagnostic role in rheumatoid arthritis