Isoliquiritigenin limits inflammasome activation of macrophage via docking into Syk to alleviate murine non-alcoholic fatty liver disease.

Isoliquiritigenin (ISL) is a chalcone-type flavonoid derived from the root of licorice with antioxidant, anti-inflammatory, anti-tumour and neuroprotective properties. ISL has been proven to downregulate the productions of IL-1ß, TNF-α and IL-6 by macrophages. However, detailed molecular mechanisms of this modulation remain elusive. Here, ISL suppressed Syk phosphorylation and CD80, CD86, IL-1ß, TNF-α and IL-6 expressions in lipopolysaccharide-stimulated macrophages ex vivo. ApoC3-transgenic (ApoC3TG) mice had more activated macrophages. ISL was also able to downregulate the inflammatory activities of macrophages from ApoC3TG mice. Administration of ISL inhibited Syk activation and inflammatory activities of macrophages in ApoC3TG mice in vivo. The treatment of ISL further alleviated MCD-induced non-alcoholic fatty liver disease (NAFLD) in wild-type and ApoC3TG mice, accompanied by less recruitment and activation of liver macrophages. Due to the inhibition of Syk phosphorylation, ISL-treated macrophages displayed less production of cytoplasmic ROS, NLRP3, cleaved-GSDMD and cleaved-IL-1ß, suggesting less inflammasome activation. Finally, the molecular docking study demonstrated that ISL bound to Syk directly with the Kd of 1.273 × 10-8 M. When the Syk expression was knocked down by its shRNA, the inhibitory effects of ISL on activated macrophages disappeared, indicating that Syk was at least one of key docking-molecules of ISL. Collectively, ISL could alleviate MCD-induced NAFLD in mice involved with the inhibition of macrophage inflammatory activity by the blockade of Syk-induced inflammasome activation.

Apolipoprotein C-III itself stimulates the Syk/cPLA2-induced inflammasome activation of macrophage to boost anti-tumor activity of CD8+ T cell.

Increased prevalence of cancer in obese individuals is involved with dyslipidemia- induced chronic inflammation and immune suppression. Although apolipoprotein C-III (ApoC3)-transgenic mice (ApoC3TG mice) or poloxamer 407 (P407)-treated mice had hyperlipidemia, CD8+ T cells with upregulated antitumor activities were observed in ApoC3TG mice, and decreased CD8+ T cell activities were observed in P407-treated mice. Increased ApoC3 expression in hepatocellular carcinoma was associated with increased infiltration of CD8+ T cells and predicted survival. Recombinant ApoC3 had no direct effects on CD8+ T cells. The upregulation of CD8+ T cells in ApoC3TG mice was due to cross-talk with context cells, as indicated by metabolic changes and RNA sequencing results. In contrast to dendritic cells, the macrophages of ApoC3TG mice (macrophagesTG) displayed an activated phenotype and increased IL-1ß, TNF-α, and IL-6 production. Coculture with macrophagesTG increased CD8+ T cell function, and the adoptive transfer of macrophagesTG suppressed tumor progression in vivo. Furthermore, spleen tyrosine kinase (Syk) activation induced by TLR2/TLR4 cross-linking after ApoC3 ligation promoted cellular phospholipase A2 (cPLA2) activation, which in turn activated NADPH oxidase 2 (NOX2) to promote an alternative mode of inflammasome activation. Meanwhile, mitochondrial ROS produced by increased oxidative phosphorylation of free fatty acids facilitated the classical inflammasome activation, which exerted an auxiliary effect on inflammasome activation of macrophagesTG. Collectively, the increased antitumor activity of CD8+ T cells was mediated by the ApoC3-stimulated inflammasome activation of macrophages, and the mimetic ApoC3 peptides that can bind TLR2/4 could be a future strategy to target liver cancer.

Low-dose adropin stimulates inflammasome activation of macrophage via mitochondrial ROS involved in colorectal cancer progression.

Adropin is encoded by the energy homeostasis-associated (ENHO) gene and widely present in liver, pancreas, heart, kidney, brain, and vascular tissues. Abnormal adropin is associated with metabolic, inflammatory, immune, and central nervous disorders. Whether adropin is involved in the development of colorectal cancer (CRC) is still unclear. Here, decreased adropin expression of tumor-nest cells in advanced-stage CRC was demonstrated. Adropin expressed by carcinoma cells was negatively correlated with macrophage infiltration in the matrix of CRC tissues. However, tumor macrophages enhanced adropin expression and were positively correlated with tumor invasion and metastasis. ENHO gene transfection into colon cancer (MC38) cells inhibited tumor growth in vivo, accompanying the increase of M1 macrophages. Treatment with low-dose adropin (< 100 ng/mL) on macrophages ex vivo directly increased mitochondrial reactive oxygen species for inflammasome activation. Furthermore, ENHO-/- mice had less M1 macrophages in vivo, and ENHO-/- macrophages were inert to be induced into the M1 subset ex vivo. Finally, low-dose adropin promoted glucose utilization, and high-dose adropin enhanced the expression of CPT1α in macrophages. Therefore, variations of adropin level in carcinoma cells or macrophages in tumor tissues are differently involved in CRC progression. Low-dose adropin stimulates the antitumor activity of macrophages, but high-dose adropin facilitates the pro-tumor activity of macrophages. Increasing or decreasing the adropin level can inhibit tumor progression at different CRC stages.

B-N/B-O Contained Heterocycles as Fusion Locker in Multi-Resonance Frameworks towards Highly-efficient and Stable Ultra-Narrowband Emission.

Fusing condensed aromatics into multi-resonance (MR) frameworks has been an exquisite strategy to modulate the optoelectronic properties, which, however, always sacrifices the small full width at half maxima (FWHM). Herein, we strategically embed B-N/B-O contained heterocycles as fusion locker into classical MR prototypes, which could enlarge the π-extension and alleviate the steric repulsion for an enhanced planar skeleton to suppress the high-frequency stretching/ scissoring vibrations for ultra-narrowband emissions. Sky-blue emitters with extremely small FWHMs of 17-18 nm are thereafter obtained for the targeted emitters, decreased by (1.4-1.9)-fold compared with the prototypes. Benefiting from their high photoluminescence quantum yields of >90 % and fast radiative decay rates of >108  s-1 , one of those emitters shows a high maximum external quantum efficiency of 31.9 % in sensitized devices, which remains 25.8 % at a practical luminance of 1,000 cd m-2 with a small FWHM of merely 19 nm. Notably a long operation half-lifetime of 1,278 h is also recorded for the same device, representing one of the longest lifetimes among sky-blue devices based on MR emitters.

Sterically Wrapped Multiple Resonance Fluorophors for Suppression of Concentration Quenching and Spectrum Broadening.

Multiple resonance (MR) emitters are promising for highly efficient organic light-emitting diodes (OLEDs) with narrowband emission; however, they still face intractable challenges with concentration-caused emission quenching, exciton annihilation, and spectral broadening. In this study, sterically wrapped MR dopants with a fluorescent MR core sandwiched by bulk substituents were developed to address the intractable challenges by reducing intermolecular interactions. Consequently, high photo-luminance quantum yields of ≥90 % and small full width at half maximums (FWHMs) of ≤25 nm over a wide range of dopant concentrations (1-20 wt %) were recorded. In addition, we demonstrated that the sandwiched MR emitter can effectively suppress Dexter interaction when doped in a thermally activated delayed fluorescence sensitizer, eliminating exciton loss through dopant triplet. Within the above dopant concentration range, the optimal emitter realizes remarkably high maximum external quantum efficiencies of 36.3-37.2 %, identical small FWHMs of 24 nm, and alleviated efficiency roll-offs in OLEDs.

Nitrogen-Embedded Multi-Resonance Heteroaromatics with Prolonged Homogeneous Hexatomic Rings.

Nitrogen-containing polycyclic heteroaromatics have exhibited fascinating multi-resonance (MR) characteristics for efficient narrowband emission, but strategies to bathochromic shift their emissions while maintaining the narrow bandwidths remain exclusive. Here, homogeneous hexatomic rings are introduced into nitrogen-embedded MR skeletons to prolong the π-conjugation length for low-energy electronic transitions while retaining the non-bonding character of the remaining parts. The proof-of-the-concept emitters exhibit near unity photoluminescence quantum yields with peaks at 598 nm and 620 nm and small full-width-at-half-maximums of 28 nm and 31 nm, respectively. Optimal organic light-emitting diodes exhibit a high external quantum efficiency of 18.2 %, negligible efficiency roll-off, and ultra-long lifetime with negligible degradation at an initial luminance of 10 000 cd m-2 after 94 hours.

One-Shot Synthesis of B/N-Doped Calix[4]arene Exhibiting Narrowband Multiple Resonance Fluorescence.

A novel macrocycle of B/N-doped calix[4]arene (C-BN) was synthesized by a one-shot double boronation. Owing to the structural tension and electron-donating properties of the nitrogen atoms in the macrocycle, reaction selectively proceeds between the adjacent benzene rings outside the macrocycle. C-BN shows a highly centrosymmetric structure with two multiple resonance (MR) fragments bridged by tertiary amine groups at the 1,3 positions of the benzene ring. Benefiting from the large intermolecular distance (>4.6 Å) between adjacent MR-emitting cores, C-BN also exhibits excellent narrowband emitting features against aggregation-induced quenching and spectrum broadening. Optimized organic light-emitting diode devices based on C-BN exhibit high maximum external quantum efficiencies of 24.7-26.6 % and small full width at half maximums of 25-28 nm over a wide doping range of 1-12 wt %.

Deficiency of miR-15a/16 upregulates NKG2D in CD8+ T cells to exacerbate dextran sulfate sodium-induced colitis.

The miR-15a/16 gene cluster is located in human chromosome 13 (13q14.3) and mouse chromosome 14 (14qC3). These genes are involved in cancer development and immune regulation. Our group has previously verified the binding of the 3'-untranslated region of NKG2D gene by miR-16 through dual-luciferase reporter assay. Herein, we found that miR-16 overexpression inhibited the NKG2D expression of CD8+ T cells, and that CD8+ NKG2D+ T cell frequency increased in miR-15/16-/- mice. CD8+ NKG2D+ T cells derived of miR-15/16-/- mice displayed activatory phenotype with enhanced IFN-γ production and cytotoxicity. The transfection of lentivirus containing antago-miR-16 sequences enhanced the NKG2D expression level of CD8+ T cells. However, no significant differences in CD8+ NKG2D+ T cell frequencies existed between wild-type and miR-15/16-transgenic mice because NKG2D was not expressed on the rest CD8+ T cells. When CD8+ T cells of miR-15/16-transgenic mice were treated with IL-2 in vitro, the magnitude of NKG2D expression and activation of CD8+ T cells was lower than that of wild-type mice. miR-15/16-/- mice showed that the exacerbation of colitis induced by dextran sulfate sodium (DSS) with more CD8+ T cells accumulated in inflamed colons, whereas miR-15/16-transgenic mice ameliorated DSS-induced colitis with less infiltration of CD8+ T cells. When NKG2D+ cells were depleted with NKG2D antibody in miR-15/16-/- mice, the aggravated colitis disappeared. All these results demonstrated that NKG2D could be upregulated by decreased miR-16 in CD8+ T cells to mediate inflammation. Thus, gene therapy based on the overexpression of miR-16 in CD8+ T cells can be used for patients with inflammatory diseases.

MiR-15a/16-1 deficiency induces IL-10-producing CD19+ TIM-1+ cells in tumor microenvironment.

IL-10-producing B cells (B10) are associated with autoimmune diseases, infection and tumours. MiR-15a/16 as a tumour-suppressive gene is down-regulated in several tumours, such as chronic lymphocytic leukaemia, pituitary adenomas and prostate carcinoma. Here, increased frequency of IL-10-producing CD19+ Tim-1+ cells was seen in both aged miR-15a/16-/- mice (15-18 months) with the onset of B cell leukaemia and young knockout mice (8-12 weeks) transplanted with hepatic cancer cells. CD19+ Tim-1+ cells down-regulated the function of effector CD4+ CD25low T cells ex vivo dependent on IL-10 production, and adoptive transfer of CD19+ Tim-1+ cells promoted tumour growth in mice. IL-10 production by CD19+ Tim-1+ cells was involved with the STAT3 activation. Bioinformatics analysis shows that miR-16 targets the 3'-untranslating region (3'-UTR) of STAT3 mRNA. Overexpression of miR-16 in CD19+ Tim-1+ cells inhibited STAT3 transcription and its protein expression. Thus, the loss of miR-15a/16 promoted induction of regulatory CD19+ Tim-1+ cells in tumour microenvironment. These results confirmed that miR-15a/16 could be used in tumour therapy due to its inhibition of tumour and regulatory B cells.

Regulatory NK1.1-CD4+NKG2D+ subset induced by NKG2DL+ cells promotes tumor evasion in mice.

Regulatory T cells play critical roles in self-tolerance and tumor evasion. CD4+NKG2D+ cells with regulatory activity are present in patients with NKG2DL+ tumors and juvenile systemic lupus erythematosus. We previously showed that TGF-ß-producing CD4+NKG2D+ T cells are present in pCD86-Rae-1ε transgenic mice. Here, we performed both ex vivo and in vivo studies on pCD86-Rae-1ε transgenic mice and an MC38 tumor-bearing mouse model and show that NK1.1-CD4+NKG2D+ T cells have regulatory activity in pCD86-Rae-1ε transgenic mice. Furthermore, this T-cell subset was induced in mice transplanted with NKG2DL+ tumor cells and produced TGF-ß and FasL, and secreted low amounts of IFN-γ. This T-cell subset downregulated the function of effector T cells and dendritic cells, which were abolished by anti-TGF-ß antibody. In vivo, adoptive transfer of NK1.1-CD4+NKG2D+ T cells promoted TGF-ß-dependent tumor growth in mice. We further found that ex vivo induction of NK1.1-CD4+NKG2D+ T cells was dependent on both anti-CD3 and NKG2DL stimulation. Furthermore, regulatory NK1.1-CD4+NKG2D+ T cells did not express Foxp3 or CD25 and expressed intermediate levels of T-bet. Western-blotting showed that STAT3 signaling was activated in NK1.1-CD4+NKG2D+ T cells of MC38 tumor-bearing and pCD86-Rae-1ε transgenic mice. In conclusion, we describe a regulatory NK1.1-CD4+NKG2D+ T-cell population, different from other regulatory T cells and abnormally elevated in pCD86-Rae-1ε transgenic and MC38 tumor-bearing mice.

Increased M1 macrophages in young miR-15a/16-/- mice with tumour grafts or dextran sulphate sodium-induced colitis.

M1 macrophages are involved in inflammation by producing proinflammatory cytokines, whereas M2 macrophages are associated with wound healing and tissue regeneration by producing anti-inflammatory cytokines. MicroRNAs are involved in macrophage polarization. To evaluate whether miR-15a/16 is involved in macrophage polarization under tumour or inflammation microenvironments, we observed the growth of transplanted hepatic cancer (H22) cells or severity of dextran sulphate sodium (DSS)-induced colitis in 8-week-old miR-15a/16 knockout (KO) mice. Compared with littermate controls, the miR-15a/16-/- mice exhibited retarded tumour growth and increased sensibility to DSS-induced colitis. Meanwhile, the M1 cell frequencies were higher in tumour tissues and inflamed colons of KO mice than of littermate controls. Macrophages with miR-15a/16 deletion revealed an enhanced NF-κB transcription under the physiological state and lipopolysaccharide (LPS) or high mobility group box 1 (HMGB1) stimulation. STAT3 expression was also significantly increased in miR-15a/16-/- macrophages under LPS or HMGB1 stimulation. The polarization of M1 macrophages can be associated with the coactivation of NF-κB and STAT3. Results indicated that miR-15a/16 deficiency in the macrophages directs M1 polarization for tumour suppression and proinflammation. Thus, miR-15a/16 deletion in macrophages holds a distinct biological significance from that of the microRNA deficiency in tumour cells.

NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid-derived suppressor cells in mice.

Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8+ T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D-mediated immune cell activation, such as tumour-derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down-regulate the expression of NKG2D on NK cells and CD8+ T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b+ Gr-1+ myeloid-derived suppressor cell (MDSC) via NKG2D in vitro and in vivo. MDSCs induced by RAE1ε display a robust induction of IL-10 and arginase, and these MDSCs show greater suppressive activity by inhibiting antigen-non-specific CD8+ T-cell proliferation. Consistently, upon adoptive transfer, MDSCs induced by RAE1ε significantly promote CT26 tumour growth in IL-10- and arginase-dependent manners. RAE1ε moves cytokine balance towards Th2 but not Th1 in vivo. Furthermore, RAE1ε enhances inhibitory function of CT26-derived MDSCs and promotes IL-4 rather than IFN-γ production from CT26-derived MDSCs through NKG2D in vitro. Our study has demonstrated a novel mechanism for NKG2D ligand+ tumour cells escaping from immunosurveillance by facilitating the proliferation and the inhibitory function of MDSCs.

Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation.

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment.

Immune complex negatively regulates toll-like receptor 3-triggered tumour necrosis factor α production in B cells.

Inappropriate activation of toll-like receptor 3 (TLR3) has been implicated in the pathogenesis of autoimmune diseases, so the negative regulation of TLR3-triggered immune response has received increasing attention. Nonpathogenic immune complex (IC) has been used as treatment for many inflammatory and autoimmune diseases. However, the role of IC in the regulation of TLR3-triggered immune responses and the underlying mechanisms need to be investigated. In this study we demonstrate that IC or intravenous immunoglobulin (Ig) stimulation of B cells attenuates polyinosinic:polycytidylic acid (poly I:C)-induced CD40 expression; IC, but not Ig, can significantly inhibit poly I:C-induced pro-inflammatory tumour necrosis factor α (TNF-α) production by B cells. Moreover, IC/Ig stimulation does not alter the expression of TLR3 in B cells. Further experiments suggest that receptor for the Fc portion of IgGIIb (FcγRIIb) is involved in the suppressive effect of IC on TLR3-mediated TNF-α production, but not CD40 expression. Thus, we provide a new means of negative regulation of TLR3-triggered immune responses in B cells via FcγRIIb, and we provide a new mechanistic explanation of the therapeutic effect of nonpathogenic IC on inflammatory or autoimmune diseases.

MiR-16 regulates mouse peritoneal macrophage polarization and affects T-cell activation.

MiR-16 is a tumour suppressor that is down-regulated in certain human cancers. However, little is known on its activity in other cell types. In this study, we examined the biological significance and underlying mechanisms of miR-16 on macrophage polarization and subsequent T-cell activation. Mouse peritoneal macrophages were isolated and induced to undergo either M1 polarization with 100 ng/ml of interferon-γ and 20 ng/ml of lipopolysaccharide, or M2 polarization with 20 ng/ml of interleukin (IL)-4. The identity of polarized macrophages was determined by profiling cell-surface markers by flow cytometry and cytokine production by ELISA. Macrophages were infected with lentivirus-expressing miR-16 to assess the effects of miR-16. Effects on macrophage-T cell interactions were analysed by co-culturing purified CD4(+) T cells with miR-16-expressing peritoneal macrophages, and measuring activation marker CD69 by flow cytometry and cytokine secretion by ELISA. Bioinformatics analysis was applied to search for potential miR-16 targets and understand its underlying mechanisms. MiR-16-induced M1 differentiation of mouse peritoneal macrophages from either the basal M0- or M2-polarized state is indicated by the significant up-regulation of M1 marker CD16/32, repression of M2 marker CD206 and Dectin-1, and increased secretion of M1 cytokine IL-12 and nitric oxide. Consistently, miR-16-expressing macrophages stimulate the activation of purified CD4(+) T cells. Mechanistically, miR-16 significantly down-regulates the expression of PD-L1, a critical immune suppressor that controls macrophage-T cell interaction and T-cell activation. MiR-16 plays an important role in shifting macrophage polarization from M2 to M1 status, and functionally activating CD4(+) T cells. This effect is potentially mediated through the down-regulation of immune suppressor PD-L1.

Immune complex negatively regulates Toll-like receptor 9-mediated immune responses in B cells through the inhibitory Fc-gamma receptor IIb.

Because inappropriate activation of Toll-like receptor 9 (TLR9) may induce pathological damage, negative regulation of the TLR9-triggered immune response has attracted considerable attention. Nonpathogenic immune complex (IC) has been demonstrated to have beneficial therapeutic effects in some kinds of autoimmune diseases. However, the role of IC in the regulation of TLR9-triggered immune responses and the underlying mechanisms remain unclear. In this study, it was demonstrated that IC stimulation of B cells not only suppresses CpG-oligodeoxynucleotide (CpG-ODN)-induced pro-inflammatory IL-6 and IgM κ production, but also attenuates CD40 and CD80 expression. Furthermore, our results suggest that the receptor for the Fc portion of IgG (FcγR) IIb is involved in the suppressive effect of IC on TLR9-mediated CD40, CD80 and IL-6 expression. Finally, it was found that IC down-regulates TLR9 expression in CpG-ODN activated B cells. Our results provide an outline of a new pathway for the negative regulation of TLR9-triggered immune responses in B cells via FcγRIIb. A new mechanistic explanation of the therapeutic effect of nonpathogenic IC on inflammatory and autoimmune diseases is also provided.

CD4(+) NKG2D(+) T cells induce NKG2D down-regulation in natural killer cells in CD86-RAE-1ε transgenic mice.

The binding of NKG2D to its ligands strengthens the cross-talk between natural killer (NK) cells and dendritic cells, particularly at early stages, before the initiation of the adaptive immune response. We found that retinoic acid early transcript-1ε (RAE-1ε), one of the ligands of NKG2D, was persistently expressed on antigen-presenting cells in a transgenic mouse model (pCD86-RAE-1ε). By contrast, NKG2D expression on NK cells, NKG2D-dependent cytotoxicity and tumour rejection, and dextran sodium sulphate-induced colitis were all down-regulated in this mouse model. The down-regulation of NKG2D on NK cells was reversed by stimulation with poly (I:C). The ectopic expression of RAE-1ε on dendritic cells maintained NKG2D expression levels and stimulated the activity of NK cells ex vivo, but the higher frequency of CD4(+) NKG2D(+) T cells in transgenic mice led to the down-regulation of NKG2D on NK cells in vivo. Hence, high levels of RAE-1ε expression on antigen-presenting cells would be expected to induce the down-regulation of NK cell activation by a regulatory T-cell subset.

High-Efficiency Narrowband Multi-Resonance Emitter Fusing Indolocarbazole Donors for BT. 2020 Red Electroluminescence and Ultralong Operation Lifetime.

Polycyclic heteroaromatics with multi-resonance (MR) characteristics are attractive materials for narrowband emitters in wide-color-gamut organic light-emitting diodes. However, MR emitters with pure-red colors are still rare and usually exhibit problematic spectral broadening when redshifting emission. Here, a narrowband pure-red MR emitter is reported by fusing indolocarbazole segments into a boron/oxygen-embedded skeleton, realizing BT.2020 red electroluminescence for the first time together with a high efficiency and an ultralong lifetime. The rigid indolocarbazole segment possesses a strong electron-donating ability due to its para-positioned nitrogen-π-nitrogen backbone and also enlarges the π-extension of the MR skeleton to suppress structural displacement during radiation, achieving concurrently redshifted and narrowed emission spectrum. An emission maximum at 637 nm with a full width at half-maxima of merely 32 nm (0.097 eV) is recorded in toluene. The corresponding device simultaneously exhibits CIE coordinates of (0.708, 0.292) precisely matching the BT.2020 red point, a high external quantum efficiency of 34.4% with low roll-off and an ultralong LT95 (time to 95% of the initial luminance) of >10 000 h at 1000 cd m-2 . These performance characteristics are superior even to those of state-of-the-art perovskite and quantum-dot-based devices for this specific color, paving the way toward practical applications.

Genetic polymorphism analysis of killer cell immunoglobulin-like receptor genes in the Chinese Uygur population.

Human killer cell immunoglobulin-like receptors are expressed in natural killer cells and subsets of T lymphocytes. They regulate these cells upon interaction with human leukocyte antigen class I molecules and other ligands presented by target cells. KIR gene frequencies and haplotype distributions have been shown to differ significantly between populations from different geographical regions and ethnic origins, which relates to functional variations in the immune response. We have investigated KIR gene frequencies and genotype diversities of 15 KIR genes (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, ID, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and two pseudogenes (KIR3DP1 and 2DP1) in 120 unrelated healthy individuals of the Uygur population living in the Xinjiang autonomous region of China. All individuals were typed positive for the four framework loci KIR3DL3, 2DL4, 3DL2 and KIR3DP1, while activating genes (KIR2DS1, 2DS2, 2DS3, 2DS5 and KIR3DS1) indicated some variation in this population. KIR3DS1 was found in a higher frequency in the studied population than in other groups from China. Linkage disequilibrium among KIR genes displayed a wide range. χ(2) analysis, conducted among non-ubiquitous genes, based on the KIR gene frequency data from our study population and previously published population data, revealed significant differences in the KIR2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 2DS1, 2DS2, 2DS3, 2DS5, and 3DS1 genes. A neighbor-joining phylogenic tree, built using the observed carrier frequencies data of 13 KIR loci (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 3DL1, 3DL2, 3DL3, 2DS1, 2DS2, 2DS3, 2DS5, and 3DS1), showed relationships between the population studied and other previously reported populations. The present study can therefore be valuable for enriching the ethnical gene information resources of the KIR gene pool, for population origin studies and for KIR-related clinical practice.