Explore the vast range of titles available.

Catechol O-methyltransferase (COMT) is widely distributed in nature and installs a methyl group onto one of the vicinal hydroxyl groups of a catechol derivative. Enzymes belonging to this family require two cofactors for methyl transfer: S-adenosyl-l-methionine as a methyl donor and a divalent metal cation for regiospecific binding and activation of a substrate. We have determined two high-resolution crystal structures of Rv0187, one of three COMT paralogs from Mycobacterium tuberculosis , in the presence and absence of cofactors. The cofactor-bound structure clearly locates strontium ions and S-adenosyl-l-homocysteine in the active site, and together with the complementary structure of the ligand-free form, it suggests conformational dynamics induced by the binding of cofactors. Examination of in vitro activities revealed promiscuous substrate specificity and relaxed regioselectivity against various catechol-like compounds. Unexpectedly, mutation of the proposed catalytic lysine residue did not abolish activity but altered the overall landscape of regiospecific methylation.

Virtual reality, augmented reality, quantum dot light-emitting diodes, and organic light-emitting diodes have progressed over the last two years. Key achievements in these displays are discussed in terms of device performance.

Multiple resonance (MR) thermally activated delayed fluorescence emitters have been actively studied as pure blue dopants for organic light-emitting diodes (OLEDs) because of excellent color purity and high efficiency. However, the reported MR emitter, 2,5,13,16-tetra- tert -butylindolo[3,2,1- jk ]indolo[1′,2′,3′:1,7]indolo[2,3- b ]carbazole (tDIDCz) based on bis-fused indolocarbazole framework could not demonstrate efficient triplet-to-singlet spin crossover. In this work, we report two isomeric MR emitters designed to promote triplet exciton harvesting by reconstructing the electronic structure of tDIDCz. To manage excited states, strong electron donors were introduced at the 2,5-/1,6-position of tDIDCz. As a result, 2,5-positions managed tDIDCz shows long-range charge transfer characteristics while preserving the MR nature. Quantum chemical calculation demonstrates direct spin-orbit coupling by long-range charge transfer and spin-vibronic coupling assisted reverse intersystem crossing by short-range charge transfer simultaneously contribute to triplet-to-singlet spin crossover. Consequently, high performance blue OLED recorded a high external quantum efficiency of 30.8% at a color coordinate of (0.13, 0.13). Multi resonance thermally activated delayed fluorescence emitters are the next-generation blue dopants for organic light-emitting diodes. Here, the authors develop two isomeric emitters with hybridized long-range and short-range charge transfer excited states and realize device efficiency of 30.8%.

Agonists of glucocorticoid receptor (GR) are frequently given to cancer patients with platinum-containing chemotherapy to reduce inflammation, but how GR influences tumor growth in response to platinum-based chemotherapy such as cisplatin through inflammation-independent signaling remains largely unclear. Combined genomics and transcription factor profiling reveal that MAST1, a critical platinum resistance factor that reprograms the MAPK pathway, is upregulated upon cisplatin exposure through activated transcription factor GR. Mechanistically, cisplatin binds to C622 in GR and recruits GR to the nucleus for its activation, which induces MAST1 expression and consequently reactivates MEK signaling. GR nuclear translocation and MAST1 upregulation coordinately occur in patient tumors collected after platinum treatment, and align with patient treatment resistance. Co-treatment with dexamethasone and cisplatin restores cisplatin-resistant tumor growth, whereas addition of the MAST1 inhibitor lestaurtinib abrogates tumor growth while preserving the inhibitory effect of dexamethasone on inflammation in vivo. These findings not only provide insights into the underlying mechanism of GR in cisplatin resistance but also offer an effective alternative therapeutic strategy to improve the clinical outcome of patients receiving platinum-based chemotherapy with GR agonists. Glucocorticoid receptor (GR) agonists - used in the treatment of solid malignant tumors to reduce inflammation - could potentially affect the anti-tumor activity of chemotherapy. Here, the authors identify a mechanism of cisplatin resistance observed with GR agonist treatment, and show the binding and activation of GR by cisplatin, which leads to MAST1 activation and subsequent MAPK re-activation.

Background Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and has a poor prognosis. Identifying biomarkers based on molecular mechanisms is critical for early diagnosis, timely treatment, and improved prognosis of lung cancer. MALAT1 has been reported to have overexpressed and tumor-promoting functions in NSCLC. It has been proposed as a potential biomarker for the diagnosis and prognosis of cancer. Therefore, this study was conducted to profile the changes in gene expression according to the regulation of expression of MALAT1 in NSCLC cell lines and to investigate the correlation through bioinformatic analysis of differentially expressed genes (DEGs). Methods MALAT1 expression levels were measured using RT-qPCR. The biological functions of MALAT1 in NSCLC were analyzed by cell counting, colony forming, wound-healing, and Transwell invasion assays. In addition, gene expression profiling in response to the knockdown of MALAT1 was analyzed by transcriptome sequencing, and differentially expressed genes regulated by MALAT1 were performed by GO and KEGG pathway enrichment analyses. Bioinformatic databases were used for gene expression analysis and overall survival analysis. Results Comparative analysis versus MALAT1 expression in MRC5 cells (a normal lung cell line) and the three NSCLC cell lines showed that MALAT1 expression was significantly higher in the NSCLC cells. MALAT1 knockdown decreased cell survival, proliferation, migration, and invasion in all three NSCLC cell lines. RNA-seq analysis of DEGs in NSCLC cells showed 198 DEGs were upregulated and 266 DEGs downregulated by MALAT1 knockdown in all three NSCLC cell lines. Survival analysis on these common DEGs performed using the OncoLnc database resulted in the selection of five DEGs, phosphoglycerate mutase 1 ( PGAM1 ), phosphoglycerate mutase 4 ( PGAM4 ), nucleolar protein 6 ( NOL6 ), nucleosome assembly protein 1 like 5 ( NAP1L5 ), and sestrin1 ( SESN1 ). The gene expression levels of these selected DEGs were proved to gene expression analysis using the TNMplot database. Conclusion MALAT1 might function as an oncogene that enhances NSCLC cell survival, proliferation, colony formation, and invasion. RNA-seq and bioinformatic analyses resulted in the selection of five DEGs, PGAM1 , PGAM4 , NOL6 , NAP1L5 , and SESN1 , which were found to be closely related to patient survival and tumorigenesis. We believe that further investigation of these five DEGs will provide valuable information on the oncogenic role of MALAT1 in NSCLC.

Radiotherapy is one of the major cancer treatment strategies. Exposure to penetrating radiation causes cellular stress, directly or indirectly, due to the generation of reactive oxygen species, DNA damage, and subcellular organelle damage and autophagy. These radiation-induced damage responses cooperatively contribute to cancer cell death, but paradoxically, radiotherapy also causes the activation of damage-repair and survival signaling to alleviate radiation-induced cytotoxic effects in a small percentage of cancer cells, and these activations are responsible for tumor radio-resistance. The present study describes the molecular mechanisms responsible for radiation-induced cellular stress response and radioresistance, and the therapeutic approaches used to overcome radioresistance.

Recent studies have shown that turbidity in construction site runoff can be greatly reduced by chemical turbidity control. This study evaluated the performance of chitosan-based biopolymer (dual polymer system, DPS) vs. anionic polyacrylamide (PAM) for turbidity reduction and characteristics of flocculated sediments using two soils from North Carolina, USA. The soils were Coastal Plain sand (CPS) and Piedmont Sandy loam (PSL), representing smectitic and kaolinitic mineralogy, respectively. A series of jar tests for DPS (charging agent + chitosan) and two commercial PAM products were conducted to find optimal concentration for turbidity reduction in the respective soil suspension (20 g L−1 in soil loading). After determining the optimal flocculant concentrations, the soil suspensions treated with DPS, PAM, and no flocculant (control) were investigated for turbidity change over settling time, floc stability, floc growth, settleable solids through Imhoff cone test, and particle size distribution by a laser diffraction method. Both flocculants were effective in reducing turbidity (> 90%) in PSL suspensions while PAM outperformed DPS in CPS suspension. Settleable solids volumes increased with flocculant treatments by 23–41% relative to untreated soil suspensions (13 mL for CPS and 20 mL for PSL), indicating efficacy of flocculant-assisted particle settlings. PAM-treated particle size was greater (115 µm, median diameter) than DPS (84 µm) in PSL suspension, both being 3–5 times greater than untreated suspension (24 µm). Repeated stirring resulted in floc growth with PAM but not with DPS. Our results suggested that practitioners using flocculants to treat turbid water in construction site need to perform tests with different flocculants to determine the optimal treatment on their project. While PAM has advantage over DPS as a single flocculant treatment, DPS could be an alternative due to its eco-friendly features.

The development of highly efficient and deep blue emitters satisfying the color specification of the commercial products has been a challenging hurdle in the organic light‐emitting diodes (OLEDs). Here, deep blue OLEDs with a narrow emission spectrum with good color stability and spin‐vibronic coupling assisted thermally activated delayed fluorescence are reported using a novel multi‐resonance (MR) emitter built on a pure organic‐based molecular platform of fused indolo[3,2,1‐ jk ]carbazole structure. Two emitters derived from 2,5,11,14‐tetrakis(1,1‐dimethylethyl)indolo[3,2,1‐ jk ]indolo[1′,2′,3′:1,7]indolo[3,2‐ b ]carbazole (tBisICz) core are synthesized as the MR type thermally activated delayed fluorescence emitters realizing a very narrow emission spectrum with a full‐width‐at‐half‐maximum (FWHM) of 16 nm with suppressed broadening at high doping concentration. The tBisICz core is substituted with a diphenylamine or 9‐phenylcarbazole blocking group to manage the intermolecular interaction for high efficiency and narrow emission. The deep blue OLEDs achieve high external quantum efficiency (EQE) of 24.9%, small FWHM of 19 nm, and deep blue color coordinate of (0.16, 0.04) with good color stability with increase in doping concentration. To the authors’ knowledge, the EQE in this work is one of the highest values reported for the deep blue OLEDs that achieve the BT.2020 standard.

There are several reports in the literature on the association between non-arteritic retinal artery occlusion (NA-RAO) and acute ischemic stroke. We investigated the burden of small vessel disease (SVD) and cerebral coincident infarction observed on cerebral magnetic resonance imaging (MRI) in patients with newly diagnosed NA-RAO. In this retrospective, observational, case-series study, consecutive patients with NA-RAO who underwent cerebral MRI within one month of diagnosis between September 2003 and October 2018 were included. The classification of NA-RAO was based on ophthalmologic and systemic examinations. We also investigated the co-incident infarction and burden of underlying SVD, which were categorized as white matter hyperintensity lesion (WMH), cerebral microbleeds (CMB), and silent lacunar infarction (SLI). Among the 272 patients enrolled in the study, 18% presented co-incident infarction and 73% had SVD, which included WMH (70%), CMB (14%), and SLI (30%). Co-incident infarction, WMH, and SLI significantly increased with age: co-incident infarction was observed in 8% of young (< 50 years) patients and 30% of old (≥ 70 years) patients. The embolic etiology of RAO (large artery atherosclerosis, cardioembolism, and undetermined etiology) was significantly associated with the prevalence of SVD (82%: 70%: 64%, P  = 0.002) and co-incident infarction (30%: 19%: 8%; P  = 0.009). Therefore, high co-incidence of acute cerebral infarction and underlying SVD burden warrant careful neurologic examination and appropriate brain imaging, followed by management of NA-RAO. Urgent brain imaging is particularly pertinent in elderly patients with NA-RAO.

In this study, a multiple‐resonance (MR) core structure is developed with a spin‐flip‐restricted emission mechanism based on a fused indolo[3,2,1‐jk]carbazole (ICz) framework as emitters to improve the lifetime of blue organic light‐emitting diodes. The molecular skeleton modulation approach applied to the conjugated π‐system effectively stabilizes the triplet energy of the fused ICz emitters and narrows the full‐width‐at‐half maximum (<20 nm). In addition, the emitters exhibit higher exciton stability than conventional boron‐based MR emitters. The fused ICz‐based blue fluorescent device exhibits a high external quantum efficiency of 7.2%, a blue index of 68.6 cd A−1 at a Commission internationale de l'éclairage y coordinate (CIEy) of 0.075, and a device lifetime 1.8 times longer than that of a boron‐based emitter. In addition, a phosphor‐sensitized fluorescent device based on the ICz emitter exhibited an improved external quantum efficiency of 20.6% with a CIEy coordinate of 0.076. A multiple‐resonance thermally activated delayed fluorescence emitter with a spin‐flip‐restricted emission mechanism based on a fused indolo[3,2,1‐jk]carbazole (ICz) framework is developed as an emitter to improve the lifetime of blue organic light‐emitting diodes.