Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development

Background: The advent of novel molecular targets has dramatically changed the treatment landscape of lung cancer in recent years. Isochorismatase domain-containing protein 1 (ISOC1) has been reported as a potential biomarker in gastrointestinal cancer, while its function in lung cancer has not been determined.Methods: The expression levels and prognostic significance of ISOC1 were assessed using bioinformatic analysis. Overexpression of ISOC1 and miR-4633, and knockdown of ISOC1 in non-small cell lung cancer (NSCLC) cell lines were generated by lentiviral infection with overexpressed or shRNA plasmids. CRISPR/Cas9 system was applied to knockout ISOC1 in A549 cells. The functions of ISOC1 and miR-4633 in lung cancer development were investigated using cell proliferation, migration, and invasion assays. Xenograft tumor growth assays in nude mice were further assessed the effect of ISOC1 in the tumorigenesis of NSCLC in vivo. Cell cycle distribution analysis was performed to uncover the underlying mechanism of ISOC1 and miR-4633 in promoting NSCLC cell proliferation. Co-immunoprecipitation combined with mass spectrometry and RNA sequencing were performed to uncover the potential mechanism of ISOC1 in lung cancer development.Results: Our results found that ISOC1 expression was upregulated in NSCLC tissues and that increased expression of ISOC1 was significantly associated with worse disease-free survival in NSCLC patients. Overexpression of ISOC1 could increase the proliferation, viability, migration, and invasion of NSCLC cells. Furthermore, miR-4633, located in the first intron of ISOC1, could also promote tumor cell progression and metastasis. Mice xenograft tumor assay showed that knockout of ISOC1 could significantly inhibit tumor growth in vivo. Besides, co-immunoprecipitation combined with mass spectrometry assay revealed that ISOC1 interacted with the proteins of DNA damage repair pathways and that upregulated ISOC1 expression could significantly increase the number of DNA damage lesions. RNA sequencing analysis showed that the downstream signaling pathways mediated by ISOC1 were mainly inflammation-related.Conclusions: We demonstrated that ISOC1 and its intronic miR-4633, both of them could promote NSCLC cell proliferation, migration, invasion, and cell cycle progression. ISOC1 participates in DNA damage repair and inflammation to promote lung cancer development

Molecular Cloning and Functional Characterization of a Hexokinase from the Oriental River Prawn Macrobrachium nipponense in Response to Hypoxia

Metabolic adjustment to hypoxia in Macrobrachium nipponense (oriental river prawn) implies a shift to anaerobic metabolism. Hexokinase (HK) is a key glycolytic enzyme in prawns. The involvement of HK in the hypoxia inducible factors (HIFs) pathway is unclear in prawns. In this study, the full-length cDNA for HK (MnHK) was obtained from M. nipponense, and its properties were characterized. The full-length cDNA (2385 bp) with an open reading frame of 1350 bp, encoded a 450-amino acid protein. MnHK contained highly conserved amino acids in the glucose, glucose-6-phosphate, ATP, and Mg+2 binding sites. Quantitative real-time reverse transcription PCR assays revealed the tissue-specific expression pattern of MnHK, with abundant expression in the muscle, and gills. Kinetic studies validated the hexokinase activity of recombinant HK. Silencing of HIF-1α or HIF-1β subunit genes blocked the induction of HK and its enzyme activities during hypoxia in muscles. The results suggested that MnHK is a key factor that increases the anaerobic rate, and is probably involved in the HIF-1 pathway related to highly active metabolism during hypoxia

Application Prospect of Artificial Intelligence in Rehabilitation and Management of Myasthenia Gravis

Myasthenia gravis (MG) is a chronic autoimmune disease of the nervous system, which is still incurable. In recent years, with the progress of immunosuppressive and supportive treatment, the therapeutic effect of MG in the acute stage is satisfactory, and the mortality rate has been greatly reduced. However, there is still no consensus on how to conduct long-term management of stable MG, such as guiding patients to identify relapses, practice exercise, return to work and school, etc. In the international consensus guidance for management of myasthenia gravis published by the Myasthenia Gravis Foundation of America (MGFA) in 2020, for the first time, “the role of physical training/exercise in MG” was identified as the topic of discussion. Finally, due to a lack of high-quality evidence on physical training/exercise in patients with MG, the topic was excluded after the literature review. Therefore, this paper reviewed the current status of MG rehabilitation research and the difficulties faced by stable MG patients in self-management. It is suggested that we should take advantage of artificial intelligence (AI) and leverage it to develop the data-driven decision support platforms for MG management which can be used for adverse event monitoring, disease education, chronic management, and a wide variety of data collection and analysis

Behavioral evidence for cone-based ultraviolet vision in divergent bat species and implications for its evolution

We investigated the reactions of four bat species from four different lineages to UV light: Hipposideros armiger (Hodgson, 1835) and Scotophilus kuhlii Leach, 1821, which use constant frequency (CF) or frequency modulation (FM) echolocation, respectively; and Rousettus leschenaultii (Desmarest, 1820) and Cynopterus sphinx (Vahl, 1797), cave and tree-roosting Old World fruit bats, respectively. Following acclimation and training involving aversive stimuli when exposed to UV light, individuals of S. kuhlii and C. sphinx exposed to such stimuli displayed conditioned reflexes such as body crouching, wing retracting, horizontal crawling, flying and/or vocalization, whereas individuals of H. armiger and R. leschenaultii, in most cue-testing sessions, remained still on receiving the stimuli. Our behavioral study provides direct evidence for the diversity of cone-based UV vision in the order Chiroptera and further supports our earlier postulate that, due to possible sensory tradeoffs and roosting ecology, defects in the short wavelength opsin genes have resulted in loss of UV vision in CF bats, but not in FM bats. In addition, Old World fruit bats roosting in caves have lost UV vision, but those roosting in trees have not. Bats are thus the third mammalian taxon to retain ancestral cone-based UV sensitivity in some species

Le Peuple : organe quotidien du syndicalisme

15 mars 19391939/03/15 (A19,N6625)-1939/03/15

Terrace Engineering of the Buffer Layer: Laying the Foundation of Thick GaN Drift Layer on Si Substrates

Abstract Vertical GaN‐on‐Si devices are promising for the next‐generation high‐voltage power electronics with low cost and high efficiency. However, their applications are impeded by the limited thickness of crack‐free GaN layers and high threading dislocation density (TDD) in the layer. Buffer layers are crucial for stress control while they usually behave with poor surface morphology, which causes early stress relaxation in GaN and limited thickness. Hereby, a terrace engineering approach for the buffer layers is proposed. Through tuning the supersaturation ratio, the terrace width can be manipulated and an atomically smooth AlGaN buffer layer can be realized, which effectively reduces the compressive stress relaxation and provides a firm foundation for thick GaN growth. As a result, a 7.5 µm thick GaN drift layer with TDD as low as 8.6 × 107 cm−2 is achieved on Si substrates. The room temperature electron mobility of the GaN drift layer can be raised up to 1210 cm2 V−1 s−1. The fabricated PiN diode shows a high breakdown voltage of 1058 V as well as a high on/off ratio of 1012. This work thus truly demonstrates the potential of high‐performance and low‐cost GaN‐based electronic as well as optoelectronic devices on Si platforms

Additional file 4: Figure S1. of De novo transcriptome sequencing and analysis of male and female swimming crab (Portunus trituberculatus) reproductive systems during mating embrace (stage II)

qRT-PCR was performed for 4 genes that were identified as differentially expressed between the immature and mature male reproductive systems. The Y axis shows the relative mRNA expression levels. * p < 0.05 ** p < 0.01. (PDF 1694 kb