Alternative splicing (AS) has emerged as a key event in tumor development and microenvironment formation. However, comprehensive analysis of AS and its clinical significance in head and neck squamous ...cell carcinoma (HNSC) is urgently required.
Genome-wide profiling of AS events using RNA-Seq data from The Cancer Genome Atlas (TCGA) program was performed in a cohort of 464 patients with HNSC. Cancer-associated AS events (CASEs) were identified between paired HNSC and adjacent normal tissues and evaluated in functional enrichment analysis. Splicing networks and prognostic models were constructed using bioinformatics tools. Unsupervised clustering of the CASEs identified was conducted and associations with clinical, molecular and immune features were analyzed.
We detected a total of 32,309 AS events and identified 473 CASEs in HNSC; among these, 91 were validated in an independent cohort (n = 15). Functional protein domains were frequently altered, especially by CASEs affecting cancer drivers, such as PCSK5. CASE parent genes were significantly enriched in pathways related to HNSC and the tumor immune microenvironment, such as the viral carcinogenesis (FDR < 0.001), Human Papillomavirus infection (FDR < 0.001), chemokine (FDR < 0.001) and T cell receptor (FDR < 0.001) signaling pathways. CASEs enriched in immune-related pathways were closely associated with immune cell infiltration and cytolytic activity. AS regulatory networks suggested a significant association between splicing factor (SF) expression and CASEs and might be regulated by SF methylation. Eighteen CASEs were identified as independent prognostic factors for overall and disease-free survival. Unsupervised clustering analysis revealed distinct correlations between AS-based clusters and prognosis, molecular characteristics and immune features. Immunogenic features and immune subgroups cooperatively depict the immune features of AS-based clusters.
This comprehensive genome-wide analysis of the AS landscape in HNSC revealed novel AS events related to carcinogenesis and immune microenvironment, with implications for prognosis and therapeutic responses.
As an effective alternative to noble platinum electrocatalyst, earth abundant and inexpensive layered transition metal dichalcogenides (TMDs) are investigated for the hydrogen evolution reaction ...(HER). Compared with binary TMDs, the tunably composed ternary TMDs have hitherto received relatively little attention. Here, few‐layered ternary WS2(1−x)Se2x nanoribbons (NRs) with metallic 1T phases, much more catalytically active in HER, are prepared for the first time. The favorable ΔGHo introduced by the tensile region on the surface, along with the presence of local lattice distortions of the WS2(1−x)Se2x nanoribbons with metallic 1T phases, greatly promotes the HER process. These ternary NRs achieve the lowest overpotential of ≈0.17 V at 10 mA cm−2 and a Tafel slope of ≈68 mV dec−1 at a low catalyst loading (≈0.30 ± 0.02 mg cm−2). Notably, the long‐term durability suggests the potential of practical applications in acid electrolytes. The results here suggest that the ternary WS2(1−x)Se2x NRs with 1T phases are prominent alternatives to platinum‐based HER electrocatalysts.
Few‐layered ternary WS2(1–x)Se2x nanoribbons (NRs) with metallic 1T phases are prepared. The favorable Gibbs free energy for hydrogen absorption (ΔGHo) of the WS2(1–x)Se2x NRs, introduced by the tensile region and local lattice distortions, greatly promotes the hydrogen evolution reaction (HER). The results suggest that the metallic WS2(1–x)Se2x NRs are potential alternatives for HER electrocatalysts.
Copper (II) is one of the most of important cofactors for numerous enzymes and has captured broad attention due to its role as a neurotransmitters for physiological and pathological functions. In ...this article, we present a reaction-based fluorescent sensor for Cu2+ detection (NIR-Cu) with near-infrared excitation and emission, including probe design, structure characterization, optical property test and biological imaging application. NIR-Cu is equipped with a functional group, 2-picolinic ester, which hydrolyzes in the presence of Cu2+ with high selectivity over completed cations. With the experimental conditions optimized, NIR-Cu (5μM) exhibits linear response for Cu2+ range from 0.1 to 5μM, with a detection limit of 29nM. NIR-Cu also shows excellent water solubility and are highly responsive, both desirable properties for Cu2+ detection in water samples. In addition, due to its near-infrared excitation and emission properties, NIR-Cu demonstrates outstanding fluorescent imaging in living cells and tissues.
•A reaction-based sensor for Cu2+ detection with NIR excitation and emission.•The detection limit for Cu2+ is as low as 29nM in aqueous buffer.•The probe shows special selectivity for Cu2+ over other metal ions.
Optical cameras equipped with an underwater scooter can perform efficient shallow marine mapping. In this paper, an underwater image stitching method is proposed for detailed large scene awareness ...based on a scooter-borne camera, including preprocessing, image registration and post-processing. An underwater image enhancement algorithm based on the inherent underwater optical attenuation characteristics and dark channel prior algorithm is presented to improve underwater feature matching. Furthermore, an optimal seam algorithm is utilized to generate a shape-preserving seam-line in the superpixel-restricted area. The experimental results show the effectiveness of the proposed method for different underwater environments and the ability to generate natural underwater mosaics with few artifacts or visible seams.
We study the propagations of optical self-similar solutions in a tapered graded-index nonlinear-fiber amplifier with an external source through asymmetric twin-core fiber amplifiers. Various types of ...exact self-similar solutions, including the W-shaped and U-shaped solutions, trigonometric function solutions, and periodic wave solutions are found. The results show that these different types of self-similar optical structures can be generated and effectively controlled by modulating the amplitude of the source. The influences of nonlinear tunneling effects on the propagation of optical pulses are investigated as well. The obtained results may have potential applications in a tapered graded-index nonlinear-fiber amplifier with an external source.
The plant species, Sonchus wightianus DC., was historically used in China for both medicinal and dietary uses. In present study, seven new guaiane sesquiterpenoids (1–7) and one cytochalasin (8), ...along with five known guaianes (9–13) and two known cytochalasins (14 and 15), were isolated from the whole plants of S. wightianus. These guaianes showed structural variations in the substituents at C‐8 and/or C‐15, and compounds 6 and 7 are two sesquiterpenoid glycoside derivatives. Their structures were determined by extensive analysis of spectroscopic, electronic circular dichroism, and X‐ray diffraction data, and chemical method. Biological tests revealed that compounds 5 and 8 are potent and selective immunosuppressive reagents.
Abstract Despite the challenges associated with the synthesis of flexible metal‐covalent organic frameworks (MCOFs), these offer the unique advantage of maximizing the atomic utilization efficiency. ...However, the construction of flexible MCOFs with flexible building units or linkages has rarely been reported. In this study, novel flexible MCOFs are constructed using flexible building blocks and copper clusters with hydrazone linkages. The heterometallic frameworks (Cu, Co) are prepared through the hydrazone linkage coordination method and evaluated as catalysts for the oxygen evolution reaction (OER). Owing to the spatial separation and functional cooperation of the heterometallic MCOF catalysts, the as‐synthesized MCOFs exhibited outstanding catalytic activities with an overpotential of 268.8 mV at 10 mA cm –2 for the OER in 1 M KOH, which is superior to those of the reported covalent organic frameworks (COFs)‐based OER catalysts. Theoretical calculations further elucidated the synergistic effect of heterometallic active sites within the linkages and frameworks, contributing to the enhanced OER activity. This study thus introduces a novel approach to the fundamental design of flexible MCOF catalysts for the OER, emphasizing their enhanced atomic utilization efficiency.
RING-finger-type ubiquitin E3 ligase Constitutively Photomorphogenic 1 (COP1) and floral integrators such as FLOWERING LOCUS T (FT), TWIN SISTER OF FT (TSF) and SUPPRESSOR OF OVEREXPRESSION OF ...CONSTANS1 (SOC1) have been identified as regulators of stomatal movement. However, little is known about their roles and relationship in dark-induced stomatal closure. Here, we demonstrated that COP1 is required for dark-induced stomatal closure using
mutant. The
mutant closed stomata in response to exogenous nitric oxide (NO) but not hydrogen peroxide (H
O
), and H
O
but not NO accumulated in
in darkness, further indicating that COP1 acts downstream of H
O
and upstream of NO in dark-induced stomatal closure. Expression of
,
and
in wild-type (WT) plants decreased significantly with dark duration time, but this process was blocked in
. Furthermore,
,
, and
mutants accumulated NO and closed stomata faster than WT plants in response to darkness. Altogether, our results indicate that COP1 transduces H
O
signaling, promotes NO accumulation in guard cells by suppressing
,
and
expression, and consequently leads to stomatal closure in darkness. These findings add new insights into the mechanisms of dark-induced stomatal closure.
The excretory-secretory products released by the liver fluke Fasciola gigantica (FgESPs) play important roles in regulating the host immune response during the infection. Identification of hepatic ...miRNAs altered by FgESPs may improve our understanding of the pathogenesis of F. gigantica infection. In this study, we investigated the alterations in the hepatic microRNAs (miRNAs) in mice treated with FgESPs using high-throughput small RNA (sRNA) sequencing and bioinformatics analysis. The expression of seven miRNAs was confirmed by quantitative stem-loop reverse transcription quantitative PCR (qRT-PCR). A total of 1,313 miRNAs were identified in the liver of mice, and the differentially expressed (DE) miRNAs varied across the time lapsed post exposure to FgESPs. We identified 67, 154 and 53 dysregulated miRNAs at 1, 4 and 12 weeks post-exposure, respectively. 5 miRNAs (miR-126a-3p, miR-150-5p, miR-155-5p, miR-181a-5p and miR-362-3p) were commonly dysregulated at the three time points. We also found that most of the DE miRNAs were induced by FgESPs in the mouse liver after 4 weeks of exposure. These were subjected to Gene Ontology (GO) enrichment analysis, which showed that the predicted targets of the hepatic DE miRNAs of mice 4 weeks of FgESPs injection were enriched in GO terms, including cell membrane, ion binding, cellular communication, organelle and DNA damage. KEGG analysis indicated that the predicted targets of the most downregulated miRNAs were involved in 15 neural activity-related pathways, 6 digestion-related pathways, 20 immune response-related pathways and 17 cancer-related pathways. These data provide new insights into how FgESPs can dysregulate hepatic miRNAs, which play important roles in modulating several aspects of F. gigantica pathogenesis.
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