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Simultaneously fusing pyrrole and pyridine at perylene's opposite edges is facilely achieved in this work, yielding PerNN and its various derivatives. All targets demonstrate global diamagnetic ring current. Benefiting from a spatially separated donor–acceptor group within one planar skeleton, PerNN exhibits efficient narrow blue emission and columnar stacking. More importantly, its alkylated derivatives PerNN-MeCl and PerNN-MeI display anti-Kasha dual emission responsive to solvent polarity and reveal highly efficient ROS generation, paving the way to great potential applications. [ABSTRACT FROM AUTHOR]

Following the latest Permian mass extinction (LPME), abundant unusual sedimentary features and fabrics were widely distributed in Early Triassic carbonate platforms. As a unique type of carbonate grain, spheroids from the Lower Triassic are infrequently reported, yet differ significantly from giant ooids and oncoids. Griesbachian micritic spheroids are well preserved in the Lower Triassic Feixianguan Formation at the Baimiaozi (BMZ) outcrop in Beibei, Chongqing, southwestern China. These spheroids (diameter: 3.9–10.8 mm) were in a marl layer interbedded with massive oolites. They were deposited in the wave troughs of ripple marks comprising micritic clots, sparry calcite, clay minerals, organic matter and pyrite. A microbial spheroid origin is implied based on the coccoidal microbes (coccoid‐like microspherules and bacterial clump‐like microspherules), numerous pyrite framboids (indications suggest the presence of many sulphate‐reducing bacteria and the high iron content in seawater can promote nitrogen‐fixing cyanobacteria proliferation) and microbial‐derived microspherules. The dark‐coloured matrix between the spheroids primarily included microcrystalline calcite, clay minerals, organic matter and metazoan fossils. The spherical and ellipsoidal shapes of the spheroids suggested rapid accretion and lithification. As a unique carbonate depositional mode, Greisbachian spheroids may have been recorded for a palaeo‐ocean with dysoxic and calcium carbonate supersaturation shortly after the LPME. [ABSTRACT FROM AUTHOR]

Cystinosis is a severe, monogenic systemic disease caused by variants in CTNS gene. Currently, there is growing evidence that exonic variants in many diseases can affect pre‐mRNA splicing. The impact of CTNS gene exonic variants on splicing regulation may be underestimated due to the lack of routine studies at the RNA level. Here, we analyzed 59 exonic variants in the CTNS gene using bioinformatics tools and identified candidate variants that may induce splicing alterations by minigene assays. We identified six exonic variants that induce splicing alterations by disrupting the ratio of exonic splicing enhancers/exonic splicing silencers (ESEs/ESSs) or by interfering with the recognition of classical splice sites, or both. Our results help in the correct molecular characterization of variants in cystinosis and inform emerging therapies. Furthermore, our work suggests that the combination of in silico and in vitro assays facilitates to assess the effects of DNA variants driving rare genetic diseases on splicing regulation and will enhance the clinical utility of variant functional annotation. [ABSTRACT FROM AUTHOR]

[Objectives]Ship performance evaluation and optimization technology with regard to wind wave factors of real sea area is the key to ship energy efficiency design,and wind load is an important part of the environmental load of wind waves of ships in real sea area. For large container ships,the stacking mode has significant influence on the wind load characteristics of ships. In order to quantitatively study the influence rule,[Methods]series of wind tunnel tests with multiple wind speeds under full wind angle range are carried out for 10 000 TEU large container ship model with the same container loading quantity but different stacking modes. CFD numerical simulation calculation and Fujiwara's empirical formulas are applied for cross validation.[Results]Analysis results show that the shape parameters for transverse and longitudinal projected areas of ships exposed to the wind are of significant impact on wind load characteristics. Conventional stacking modes with streamlined or stepped layouts have better wind load characteristics in general. Special stacking modes with multiple vacancies on the deck occupy certain advantages in such aspects as yaw moment performance.[Conclusions] The study provides technical reference for container stacking mode design and calculation and evaluation of wind load in practical engineering.

The maximum tolerated dose (MTD) of lobaplatin as a single agent chemotherapy concurrent with intensity-modulated radiotherapy (IMRT) in Asian population with nasopharyngeal carcinoma (NPC) remains unclear. From June 2016 to December 2017, 17 patients diagnosed with stage III-IVb NPC from an Asian population were prospectively enrolled. Patients were administered lobaplatin with 25-50 mg/m2 escalation of dosage on day 1. Every 21 days (days 1, 22, and 43) during radiotherapy, cycles were repeated. We administered radiotherapy as 2.12-2.27 Gy per fraction with five daily fractions each week for 6 to 7 weeks. The evaluation of lobaplatin-related toxic effects was based on the Common Terminology Criteria for Adverse Events version 4.0. During the weekly treatment period, complete blood counts and biochemistry were performed. Dose-limiting toxicities (DLTs) were determined by the following events during any cycle in which lobaplatin was administered. Each dose group consisted of at least three cases. We proceeded to the subsequent dose group in the absence of DLT with a dose increment of 5 mg/m2 until DLT occurred. Periods from 1 week prior to the chemotherapy initiation to 3 weeks after the last chemotherapy were defined as DLT observation periods. MTD was determined by the dose that was immediately below the dose that produced DLT. After analysis, DLT occurred in three patients, including a group with two of three patients in 45 mg/m2 lobaplatin and another group with one of five patients in 40 mg/m2 lobaplatin. No grade 3-4 toxicity was observed in patients treated with lobaplatin

Abstract Background To compare the clinical effectiveness of ultrasound-guided needle release of the transverse carpal ligament (TCL) with and without corticosteroid injection in carpal tunnel syndrome (CTS). Methods From June 2016 to June 2017, 49 CTS patients (50 wrists) were included in this study. Twenty-five wrists were treated with ultrasound-guided needle release of the TCL plus corticosteroid injection (group A), and 25 wrists were treated with single ultrasound-guided needle release of the TCL (group B). The following parameters were assessed and compared including postprocedure results according to relief of symptoms, ultrasound parameters (cross-sectional area of the median nerve at the levels of pisiform, flattening ratio of median nerve at the levels of the hamate bone, and the thicknesses of TCL on the cross-section at the level of the hamate bone), and electrophysiological parameters (distal motor latency and sensory conduction velocity). Results Group A had higher overall excellent and good rate 3 months after the procedure than group B (84 vs 52%, P

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (GEF) has been used to treat nonsmall-cell lung cancer (NSCLC); yet, the curative effect of GEF was compromised by drug resistance. Herein, an EGFR aptamer-modified therapeutic strategy (Apt/(siRNA + GEF)@ZIF-8 nanoparticles (NPs)) was fabricated by employing zeolitic imidazolate framework-8 (ZIF-8)-based metal–organic frameworks for targeted delivery of GEF and EGFR siRNA to suppress the drug-resistant gene expression in tumors. Apt/(siRNA + GEF)@ZIF-8 NPs had a high loading efficiency for GEF and siRNA, and the particle size was about 75 nm with a stable crystal structure. In vitro experiments showed that GEF cooperating with siRNA could promote cell apoptosis and displayed a synergistic therapeutic effect on drug-resistant cancer cells. In vivo biodistribution study demonstrated that Apt/(siRNA + GEF)@ZIF-8 could be enriched at tumor sites successfully, which provided a basis for in vivo antitumor experiments. In vivo experiment illustrated that the NPs with good biocompatibility had a high efficiency for conquering the acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC with a tumor inhibition rate of 40.6%. Overall, the findings from this study implied that this biological target nanodrug therapy may provide a promising approach for the treatment of drug-resistant NSCLC. [ABSTRACT FROM AUTHOR]

Attention deficit is a critical symptom that impairs social functioning in adolescents with major depressive disorder (MDD). In this study, we aimed to explore the dynamic neural network activity associated with attention deficits and its relationship with clinical outcomes in adolescents with MDD. We included 188 adolescents with MDD and 94 healthy controls. By combining psychophysics, resting‐state electroencephalography (EEG), and functional magnetic resonance imaging (fMRI) techniques, we aimed to identify dynamic network features through the investigation of EEG microstate characteristics and related temporal network features in adolescents with MDD. At baseline, microstate analysis revealed that the occurrence of Microstate C in the patient group was lower than that in healthy controls, whereas the duration and coverage of Microstate D increased in the MDD group. Mediation analysis revealed that the probability of transition from Microstate C to D mediated anhedonia and attention deficits in the MDD group. fMRI results showed that the temporal variability of the dorsal attention network (DAN) was significantly weaker in patients with MDD than in healthy controls. Importantly, the temporal variability of DAN mediated the relationship between anhedonia and attention deficits in the patient group. After acute‐stage treatment, the response prediction group (RP) showed improvement in Microstates C and D compared to the nonresponse prediction group (NRP). For resting‐state fMRI data, the temporal variability of DAN was significantly higher in the RP group than in the NRP group. Overall, this study enriches our understanding of the neural mechanisms underlying attention deficits in patients with MDD and provides novel clinical biomarkers. [ABSTRACT FROM AUTHOR]