QTY code designed antibodies for aggregation prevention: A structural bioinformatic and computational study.

Therapeutic monoclonal antibodies are the most rapidly growing class of molecular medicine, and they are beneficial to the treatment of a broad spectrum of human diseases. However, the aggregation of antibodies during the process of manufacture, distribution, and storage poses significant challenges, potentially compromising efficacy and inducing adverse immune responses. We previously conceived a QTY (glutamine, threonine, tyrosine) code, a simple tool for enhancing protein water-solubility by systematically pairwise replacing hydrophobic residues L (leucine), V (valine)/I (isoleucine), and F (phenylalanine). The QTY code offers a promising alternative to traditional methods of controlling aggregation in integral transmembrane proteins. In this study, we designed variants of four antibodies applying the QTY code, changing only the ß-sheets. Through the structure-based aggregation analysis, we found that these QTY antibody variants demonstrated significantly decreased aggregation propensity compared to their wild-type counter parts. Our results of molecular dynamics simulations showed that the design by QTY code is capable of maintaining the antigen-binding affinity and structural stability. Our structural informatic and computational study suggests that the QTY code offers a significant potential in mitigating antibody aggregation.

Prognostic biomarker tumor-infiltrating lymphocytes failed to serve as a predictive biomarker for postoperative radiotherapy in completely resected pN2 non-small cell lung cancer: a retrospective analysis.

BACKGROUND: Evidence suggests that radiotherapy is a potent immunomodulator in non-small cell lung cancer (NSCLC). Conversely, it has rarely been demonstrated if immune infiltration can influence radiotherapy efficacy. Herein, we explored the effect of tumor-infiltrating lymphocytes (TILs) on the response to postoperative radiotherapy (PORT) in completely resected stage III-pN2 NSCLC. METHODS: This retrospective study included 244 patients with pathologically confirmed stage III-N2 NSCLC who underwent complete resection at our institution between 2014 and 2020. TILs were assessed with permanent full-face hematoxylin and eosin (H&E) sections and the evaluation of TILs was based on a published guideline. Patients were stratified into the TILlow or TILhigh group with a cutoff value of 50%. Kaplan-Meier method and Log-rank test were utilized to assess disease-free survival (DFS) and overall survival (OS). Univariate and multivariate Cox regression analysis were conducted to determine prognostic indicators. RESULTS: Among 244 patients, a total of 121 patients received PORT whereas 123 did not. TILs level in patients with PORT was significantly higher than that in patients without PORT (p < 0.001). High TILs level was significantly associated with an improved DFS and OS in all the entire chort (DFS, p < 0.001; OS, p = 0.001), PORT chort (DFS, p = 0.003; OS, p = 0.011) and non-PORT chort (DFS, p < 0.001; OS, p = 0.034). There were no significant survival differences between different treatment modalities in the low TILs infiltration (DFS, p = 0.244; OS, p = 0.404) and high TILs infiltration (DFS, p = 0.167; OS, p = 0.958) groups. CONCLUSIONS: TILs evaluated with H&E sections could represent a prognostic biomarker in patients with completely resected pN2 NSCLC, and high TILs infiltration was associated with favorable survival outcomes.The predictive value of TILs for PORT still need to be further explored in the future.

Modulation of Intermolecular Interactions in Organic Emitters for Highly Efficient Organic Light-Emitting Diodes.

The adverse aggregated-caused quenching (ACQ) problem of most electroluminescent materials existing in highly doped thin films is one of the key factors impeding the commercialization of high-efficiency organic light-emitting diodes (OLEDs) panel. Whereas, by delicately constructing and modulating moderate intermolecular interactions, some aggregates have been demonstrated to present distinct luminescent properties such as tunable emission spectra, improved photoluminescence quantum yields, different emission mechanism and enhanced horizontal transition dipole ratio (Θ) of emitting layer, providing feasible solution for ACQ problem. The luminescence from newly generated emissive state in aggregates is different from the traditional "isolated" molecules in organic electronics and will possess novel properties and applications. Herein, we summarize the different types of intermolecular interactions within emitter aggregates exhibiting distinct luminescent mechanisms, as well as their effects on photoluminescent and electroluminescent properties, offering reliable reference for the advancement of highly efficient OLEDs utilizing aggregated emitters.

Intraocular mRNA delivery with endogenous MmPEG10-based virus-like particles.

Virus-like particles (VLP) are a promising tool for intracellular gene delivery, yet their potential in ocular gene therapy remains underexplored. In this study, we bridged this knowledge gap by demonstrating the successful generation and application of vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped mouse PEG10 (MmPEG10)-VLP for intraocular mRNA delivery. Our findings revealed that PEG10-VLP can efficiently deliver GFP mRNA to adult retinal pigment epithelial cell line-19 (ARPE-19) cells, leading to transient expression. Moreover, we showed that MmPEG10-VLP can transfer SMAD7 to inhibit epithelial-mesenchymal transition (EMT) in RPE cells effectively. In vivo experiments further substantiated the potential of these vectors, as subretinal delivery into adult mice resulted in efficient transduction of retinal pigment epithelial (RPE) cells and GFP reporter gene expression without significant immune response. However, intravitreal injection did not yield efficient ocular expression. We also evaluated the transduction characteristics of MmPEG10-VLP following intracameral delivery, revealing transient GFP protein expression in corneal endothelial cells without significant immunotoxicities. In summary, our study established that VSVG pseudotyped MmPEG10-based VLP can transduce mitotically inactive RPE cells and corneal endothelial cells in vivo without triggering an inflammatory response, underscoring their potential utility in ocular gene therapy.

Yes-Associated Protein Targets the Transforming Growth Factor ß Pathway to Mediate High-Fat/High-Sucrose Diet-induced Arterial Stiffness.

BACKGROUND: Metabolic syndrome is related to cardiovascular diseases, which is attributed in part, to arterial stiffness; however, the mechanisms remain unclear. The present study aimed to investigate the molecular mechanisms of metabolic syndrome-induced arterial stiffness and to identify new therapeutic targets. METHODS: Arterial stiffness was induced by high-fat/high-sucrose diet in mice, which was quantified by Doppler ultrasound. Four-dimensional label-free quantitative proteomic analysis, affinity purification and mass spectrometry, and immunoprecipitation and GST (glutathione S-transferase) pull-down experiments were performed to explore the mechanism of YAP (Yes-associated protein)-mediated TGF (transforming growth factor) ß pathway activation. RESULTS: YAP protein was upregulated in the aortic tunica media of mice fed a high-fat/high-sucrose diet for 2 weeks and precedes arterial stiffness. Smooth muscle cell-specific YAP knockdown attenuated high-fat/high-sucrose diet-induced arterial stiffness and activation of TGFß-Smad2/3 signaling pathway in arteries. By contrast, Myh11CreERT2-YapTg mice exhibited exacerbated high-fat/high-sucrose diet-induced arterial stiffness and enhanced TGFß-activated Smad2/3 phosphorylation in arteries. PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) was identified as a YAP-bound phosphatase that translocates into the nucleus to dephosphorylate Smads (mothers against decapentaplegic homologs) in response to TGFß. This process was inhibited by YAP through removal of the K63-linked ubiquitin chain of PPM1B at K326. CONCLUSIONS: This study provides a new mechanism by which smooth muscle cell YAP regulates the TGFß pathway and a potential therapeutic target in metabolic syndrome-associated arterial stiffness.

Deciphering the impact of aging on splenic endothelial cell heterogeneity and immunosenescence through single-cell RNA sequencing analysis.

BACKGROUND: Aging is associated with significant structural and functional changes in the spleen, leading to immunosenescence, yet the detailed effects on splenic vascular endothelial cells (ECs) and their immunomodulatory roles are not fully understood. In this study, a single-cell RNA (scRNA) atlas of EC transcriptomes from young and aged mouse spleens was constructed to reveal age-related molecular changes, including increased inflammation and reduced vascular development and also the potential interaction between splenic endothelial cells and immune cells. RESULTS: Ten clusters of splenic endothelial cells were identified. DEGs analysis across different EC clusters revealed the molecular changes with aging, showing the increase in the overall inflammatory microenvironment and the loss in vascular development function of aged ECs. Notably, four EC clusters with immunological functions were identified, suggesting an Endothelial-to-Immune-like Cell Transition (EndICLT) potentially driven by aging. Pseudotime analysis of the Immunology4 cluster further indicated a possible aging-induced transitional state, potentially initiated by Ctss gene activation. Finally, the effects of aging on cell signaling communication between different EC clusters and immune cells were analyzed. CONCLUSIONS: This comprehensive atlas elucidates the complex interplay between ECs and immune cells in the aging spleen, offering new insights into endothelial heterogeneity, reprogramming, and the mechanisms of immunosenescence.

Revealing the generation of reactive oxygen species in hydrochar and pyrochar: Insight into rational regulation of free radicals and catalytic mechanism.

The removal of organic pollutants by biochar has been extensively studied. However, the differences in the removal mechanisms of contaminants by biochar obtained from different preparation techniques have not been thoroughly elucidated. In this study, the catalytic performances of hydrochar (HC) and pyrochar (PC) were compared in the dark and light. Owing to more persistent free radicals (PFRs), greater defects and stronger charge transfer ability on the surface, PC could produce a certain concentration of superoxide radicals (•O2-) even in the dark, making its degradation efficiency for benzoic acid (BA) 11% higher than that of HC. On the contrary, when the light was turned on, HC rather than PC can generate a higher amount of hydroxyl radical (•OH), resulting in an 11% higher degradation efficiency of BA compared to PC. The improvement of catalytic performance in HC originated from its oxygen-containing functional groups (OFGs), which was beneficial for its effective production of singlet oxygen (1O2) and ·OH under light exposure. For PC, its photocatalytic activity depended mainly on the formation of 1O2 induced by the triplet of DOM (dissolved organic matter), but the lack of oxidative ·OH in its system leads to a lower degradation efficiency than that of HC. To prove the universal applicability of this rule for biochar materials, HC and PC materials obtained from soybean residue were also prepared for degrading BA. This work is devoted to an in-depth exploration of the catalytic activation mechanism of biochar obtained by different technological methods, and can create conditions for the generation of more dominant reactive oxygen species (ROS) on biochar, thus providing the guidance for environmental remediation.

An innovative Zn3In2S6/ZnIn2S4 homojunction photocatalyst with enhanced interfacial charge transfer for the highly efficient degradation of tetracycline under visible radiation.

The interfacial charge transfer ability is a decisive factor influencing the photocatalytic performance of composite photocatalysts. Compared with heterojunctions that combine two or more semiconductors with different properties, homojunctions that combine two semiconductors with similar properties can accelerate the interfacial charge shift and achieve higher photocatalyticability. In this study, a Zn3In2S6/ZnIn2S4 homojunction photocatalyst (ZIS-5) with a Zn3In2S6 to ZnIn2S4 molar ratio of 5:1 was synthesized by selecting Zn3In2S6 nano-microspheres as the substrate material and growing ZnIn2S4 flocs on the nano-microspheres. The photocatalytic performance of the ZIS-5 homojunction was assessed by using tetracycline (TC) as a typical pollutant. The photocatalytic performance and mineralization rate of the ZIS-5 homojunction were significantly improved compared with those of Zn3In2S6 and ZnIn2S4, and its photocatalytic performance was increased by 10.2% and 20.9%, compared with Zn3In2S6 and ZnIn2S4, respectively, while the mineralization rate was enhanced by 22.78% and 43.28%, respectively. The results of the comparison experiment revealed that the interfacial electron transfer ability of the ZIS-5 homojunction is 1.6 times that of the g-C3N4/ZnIn2S4-5 heterojunction. The density functional theory (DFT) computation and Mott-Schottky plots verified the formation of an internal electric field. The toxicity analysis showed that the ZIS-5 homojunction system effectively reduced the toxicity of TC. This work supplies a valuable route for inventing catalysts with efficient photocatalytic performances.

Sulfur-Decorated Nonaromatic Amine Emitters Towards Efficient Triplet Exciton Utilization in Organic Light-Emitting Diodes.

Purely organic compounds served as promising materials for organic electronics have intrigued extensive research focuses owing to their unique photophysical and electronic properties. In the field of organic light-emitting diodes (OLEDs), the utilization of triplet excitons is of great significance for realizing high-performance devices. In contrast to the traditional aromatic amine-based counterparts, sulfur atom with a high-level outer orbit simultaneously provides powerful electron-donating ability and striking spin-orbit coupling effect to facilitate the utilization of theoretically spin-forbidden triplet excitons, demonstrating great prospect in constructing highly emissive purely organic emitters for OLED applications. Herein, we summarize the currently developed sulfur-decorated nonaromatic amine-based emitters exhibiting attractive photoelectronic characteristics, and gain insight into the understanding of molecular design and photophysical processes of these emitters, providing new perspectives for enriching the existing luminescent material systems and designing high-performance emitters.

Synthesis of Vinylene-Linked Thiopyrylium-, Pyrylium-, and Pyridinium-Based Covalent Organic Frameworks by Acid-Catalyzed Aldol Condensation.

The development of new vinylene-linked covalent organic frameworks (COFs) with special ionic structure and high stability is challenging. Herein, we report a facile, general method for constructing ionic vinylene-linked thiopyrylium-based COFs from 2,4,6-trimethylpyrylium tetrafluoroborate and other common reagents by means of acid-catalyzed Aldol condensation. Besides, pyrylium-, and pyridinium-based COFs also can be prepared from the same monomer under slightly different reaction conditions. The COFs exhibited uniform nanofibrous morphologies with excellent crystallinities, special ionic structures, well-defined nanochannels, and high specific surface areas.

Quantum manifestations in electronic properties of bilayer phosphorene nanoribbons.

Recently, a new edge structure named ZZ(U) has been evidenced as the lowest-energy structure for bilayer phosphorene nanoribbons (PNRs). Owing to strong quantum confinement effects and edge states, width and edge are the two most important factors that influence the properties of PNRs in nanosized microelectronics. In this study, we systematically investigated the evolution of the electronic properties of bilayer PNRs with different edge configurations as the widths vary. The four types of edges explored include ZZ(Pristine), ZZ(Klein), ZZ(Tube), and newly found ZZ(U). As the widths change from 14 to 40 Å, the ZZ(Pristine) are always metallic with edge states penetrating the Fermi level, while the others are semiconductors. The edge states in ZZ(Klein) are located in the two lowest conduction bands. However, in ZZ(U), the edge states are nearly hidden in the bulk band structure, and its carrier transportation exhibits almost perfect 2D layers, nearly eliminating the U-edge influence. Our results pave the way for phosphorene's utilization in electronics and optoelectronics.

Changes in gene expression and enzyme activity related to glucose metabolism in the livers of Brandt's voles (Lasiopodomys brandtii) exposed to hypoxia.

Brandt's vole (Lasiopodomys brandtii) is a hypoxia-tolerant species, and the metabolic characteristics of hypoxia-tolerant species have become a focus of recent research. However, insights into the anaerobic and aerobic metabolism of the livers of Brandt's voles under hypoxia remain limited. In this study, Brandt's voles and hypoxia-intolerant Kunming mice (Mus musculus, control species) were exposed to hypoxia conditions (Brandt's voles, 10% and 7.5% O2; Kunming mice, 10% O2) for 24 h, and changes in gene expression and enzyme activity related to anaerobic and aerobic metabolism in the livers were evaluated. Phosphofructokinase 1 (PFK1), phosphofructokinase 2 (PFK2), pyruvate kinase muscle (PKM), hexokinase 2 (HK2), and lactate dehydrogenase (LDH) related to anaerobic metabolism in the livers of Brandt's voles were increased under 7.5% O2. Regarding gene expression and enzyme activity for aerobic metabolism in Brandt's voles under 7.5% and 10% O2, pyruvate dehydrogenase kinase 1 (PDK1) expression was up-regulated, and succinate dehydrogenase (SDH) activity was decreased. In the livers of Kunming mice, gene expression related to anaerobic and aerobic metabolism was increased at the late stage of 10% O2, and SDH activity was enhanced at 6 h and reduced at 18 h. In addition, PFK1,PKM, PDK1 expression and SDH activity in Brandt's voles were significantly correlated with HIF-1a expression. PFK1, PKM, LDHand PDK1 expression in Kunming mice were significantly correlated with HIF-1a expression. These findings indicate that the livers of Brandt's voles have a certain tolerance to hypoxia, and metabolic changes play important roles in hypoxia tolerance.

Rituximab treatment for refractory nephrotic syndrome in adults: a multicenter retrospective study.

BACKGROUND: The treatment of refractory nephrotic syndrome (RNS) is full of challenges and the role of rituximab (RTX) is not well-established, thus this study aims to demonstrate the role of RTX in RNS. METHODS: This was a multicenter retrospective study of all adult patients receiving RTX for RNS. Patients enrolled were divided into two groups according to pathological pattern: 20 patients as a group of podocytopathy (including minimal change disease [MCD] and focal and segmental glomerulosclerosis [FSGS]), and 26 patients as membranous nephropathy (MN) group. The remission rate, relapse rate, adverse effects, and predictors of remission were analyzed. RESULTS: A total of 75 patients received RTX for RNS and 48 were available for analysis after exclusion criteria. No significant difference in the remission rate at 6 or 12 months was observed between the MCD/FSGS and MN cases (p > 0.05). The median duration of the first complete remission (CR) was 1 month in the podocytopathy group and 12.5 months in the MN group. Three relapses were associated with infection as the ultimate outcome, and 6 out of 48 remained refractory representing a response rate of 87.5% in RNS. Clinical predictors of cumulative CR were estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and mean arterial pressure (MAP) ≤103 mmHg at the beginning of therapy in patients with MN. No serious adverse effects were reported. CONCLUSIONS: RTX appears to be effective in RNS across various clinical and pathological subtypes, exhibiting a low relapse rate and minimal significant side effects in the majority of patients.

Cascading Affine and B-spline Registration Method for Large Deformation Registration of Lung X-rays.

Accurate registration of lung X-rays is an important task in medical image analysis. However, the conventional methods usually cost a lot in running time, and the existing deep learning methods are hard to deal with the large deformation caused by respiratory and cardiac motion. In this paper, we attempt to use deep learning methods to deal with large deformation and enable it to achieve the accuracy of conventional methods. We proposed the cascading affine and B-spline network (CABN), which consists of convolutional cross-stitch affine block (CCAB) and B-splines U-net-like block (BUB) for large lung motion. CCAB makes use of the convolutional cross-stitch model to learn global features among images. And BUB adopts the idea of cubic B-splines which is suitable for large deformation. We separately demonstrated CCAB, BUB, and CABN on two chest X-ray datasets. The experimental results indicate that our methods are highly competitive both in accuracy and runtime when compared to both other deep learning methods and iterative conventional approaches. Moreover, CCAB also can be used for the preprocessing of non-rigid registration methods, replacing affine in conventional methods.

Dynamic Dimerization of Chemokine Receptors and Potential Inhibitory Role of Their Truncated Isoforms Revealed through Combinatorial Prediction.

Chemokine receptors play crucial roles in fundamental biological processes. Their malfunction may result in many diseases, including cancer, autoimmune diseases, and HIV. The oligomerization of chemokine receptors holds significant functional implications that directly affect their signaling patterns and pharmacological responses. However, the oligomerization patterns of many chemokine receptors remain poorly understood. Furthermore, several chemokine receptors have highly truncated isoforms whose functional role is not yet clear. Here, we computationally show homo- and heterodimerization patterns of four human chemokine receptors, namely CXCR2, CXCR7, CCR2, and CCR7, along with their interaction patterns with their respective truncated isoforms. By combining the neural network-based AlphaFold2 and physics-based protein-protein docking tool ClusPro, we predicted 15 groups of complex structures and assessed the binding affinities in the context of atomistic molecular dynamics simulations. Our results are in agreement with previous experimental observations and support the dynamic and diverse nature of chemokine receptor dimerization, suggesting possible patterns of higher-order oligomerization. Additionally, we uncover the strong potential of truncated isoforms to block homo- and heterodimerization of chemokine receptors, also in a dynamic manner. Our study provides insights into the dimerization patterns of chemokine receptors and the functional significance of their truncated isoforms.

Highly efficient persulfate catalyst prepared from modified electrolytic manganese residues coupled with biochar for the roxarsone removal.

The contamination of organoarsenic is becoming increasingly prominent while SR-AOPs were confirmed to be valid for their remediation. This study has found that the novel metal/carbon catalyst (Fe/C-Mn) prepared by solid waste with hierarchical pores could simultaneously degrade roxarsone (ROX) and remove As(V). A total of 95.6% of ROX (20 mg/L) could be removed at the concentration of 1.0 g/L of catalyst and 0.4 g/L of oxidant in the Fe/C-Mn/PMS system within 90 min. The scavenging experiment and electrochemical test revealed that both single-electron and two-electron pathways contributed to the ROX decomposition. Spectroscopic analysis suggested the ROX has been successfully mineralized while As(V) was fixed with the surface Fe and Mn. Density functional theory (DFT) calculation and chromatographic analysis indicated that the As7, N8, O9 and O10 sites of ROX molecule were vulnerable to being attacked by nucleophilic, electrophilic and radical, resulting in the formation of several intermediates such as phenolic compounds. Additionally, the low metal leaching concentration during recycling and high anti-interference ability in various water matrices manifested the practicability of Fe/C-Mn/PMS system.

Screening and identification of high yield tetramethylpyrazine strains in Nongxiangxing liquor Daqu and study on the mechanism of tetramethylpyrazine production.

BACKGROUND: There are few reports on the breeding of high-yielding tetramethylpyrazine (TTMP) strains in strong-flavor Daqu. In addition, studies on the mechanism of TTMP production in strains are mostly based on common physiological and biochemical indicators, and there is no report on RNA level. Therefore, in this study, a strain with high production of TTMP was screened out from strong-flavor liquor, and transcriptome sequencing analysis was performed to analyze its key metabolic pathways and key genes, and to infer the mechanism of TTMP production in the strain. RESULTS: In this study, a strain with a high yield of tetramethylpyrazine (TTMP) was screened out, and the yield was 29.83 µg mL-1 . The identified strain was Bacillus velezensis, which could increase the content of TTMP in liquor by about 88%. After transcriptome sequencing, a total of 1851 differentially expressed genes were screened, including 1055 up-regulated genes and 796 down-regulated genes. Three pathways related to the production of TTMP were identified by gene ontology (GO) annotation and COG annotation, including carbohydrate metabolism, cell movement and amino acid metabolism. The key genes of TTMP were analyzed, and the factors that might regulate the production of TTMP, such as the transfer of uracil phosphate ribose and glycosyltransferase, were obtained. CONCLUSIONS: A strain of B. velezensis with high TTMP production was screened and identified in strong-flavor Daqu for the first time. The yield of TTMP was 29.83 µg mL-1 , which increased the TTMP content in liquor by 88%. The key metabolic pathways of TTMP production in the strain were obtained: carbohydrate metabolism, cell movement and amino acid metabolism, and the key regulatory genes of each pathway were found, which complemented the gap in gene level in the production regulation of the strain, and provided a theoretical basis for the subsequent study of TTMP in liquor. © 2023 Society of Chemical Industry.

Mild Synthesis of Polychlorinated Arenes for Efficient Organic Light-emitting Diodes with Dual Thermally Activated Delayed Fluorescence.

Polychlorinated (hetero)arenes have shown great promise for organic optoelectronics applications. However, the harsh synthetic routes for polychlorinated compounds and the possible luminescence quenching from the compact intermolecular π-π stacking induced by chlorine atoms limit their investigations and applications in luminescent materials. Herein, two isomeric polychlorinated polycyclic aromatic hydrocarbon (PAH) compounds JY-1-Cl and JY-2-Cl consisting of rigidified aryl ketones and amine are designed and synthesized under mild conditions through nucleophilic chlorination intermediated by an electron donor-acceptor complex. Among them, as a result of the strong π-π interactions induced by chlorine atoms, JY-2-Cl exhibits bright monomer and dimer emissions with dual thermally activated delayed fluorescence (TADF) characters. Notably, compared with the non-chlorinated compounds, a high photoluminescence quantum yield is maintained after introducing multiple chlorine atoms into JY-2-Cl. The first dual-TADF organic light-emitting diodes are also successfully fabricated with maximum external quantum efficiency as high as 29.1 % by employing JY-2-Cl as emitter. This work presents a new paradigm and synthesis of polychlorinated amine-carbonyl PAHs and demonstrates the great potential of the chlorinated materials for luminescent applications.

Sulfone-Embedded Heterocyclic Narrowband Emitters with Strengthened Molecular Rigidity and Suppressed High-Frequency Vibronic Coupling.

Sulfone-embedded heterocyclics are of great interest in organic light-emitting diodes (OLEDs), however, exploring highly efficient narrowband emitters based on sulfone-embedded heterocyclics remains challenging. Herein, five emitters with different sulfur valence state and molecular rigidity, namely tP, tCPD, 2tCPD, tPD and tPT, are thoroughly analysed. With restricted twisting of flexible peripheral phenyl by strengthening molecular rigidity, molecular emission spectra can be enormously narrowed. Further, introducing the sulfone group with bending vibration in low-frequency region that suppresses high-frequency vibration, sharp narrow full-widths at half-maximum of 28 and 25 nm are achieved for 2tCPD and tPD, respectively. Maximum external quantum efficiencies of 22.0 % and 27.1 % are successfully realized for 2tCPD- and tPD-based OLED devices. These results offer a novel design strategy for constructing narrowband emitters by introducing sulfone group into a rigid molecular framework.

Osteopontin is required for the maintenance of leukemia stem cells in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous hematopoietic disorder with a poor prognosis. The clinical significance of Leukemia stem cells (LSCs) plays an important role in the generation of AML and is the main cause of the recurrence after remission. Osteopontin (OPN), an extracellular matrix protein, has been implicated in hematopoietic malignancies. However, the specific role and the underlying mechanism of AML cell autocrined OPN in leukemia maintenance remain unknown. Here, we showed that knockdown of Opn expression significantly prolonged the survival of mice with MLL-AF9 cell-induced AML and markedly reduced the tumor burden. The LSCs from the Opn-knockdown groups exhibited decreased numbers and impaired function as determined by immunophenotype, colony-forming and limiting dilution assays. Further analysis revealed that Opn prevents LSCs from undergoing apoptosis and cell cycle arrest. Repression of OPN in human AML cell lines in vitro mimics the phenotypes observed in the mouse model. Overall, our data indicated that OPN is a potent therapeutic target for eradicating LSCs in AML.