Background
Large‐cell neuroendocrine carcinoma of the lung (LCNEC) and small‐cell lung carcinoma (SCLC) are neuroendocrine neoplasms. However, the underlying mechanisms of common and distinct genetic ...characteristics between LCNEC and SCLC are currently unclear. Herein, protein expression profiles and possible interactions with miRNAs were provided by integrated bioinformatics analysis, in order to explore core genes associated with tumorigenesis and prognosis in SCLC and LCNEC.
Methods
GSE1037 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in LCNEC and SCLC, as compared with normal lung tissues, were selected using the GEO2R online analyzer and Venn diagram software. Gene ontology (GO) analysis was performed using Database for Annotation, Visualization and Integrated Discovery. The biological pathway analysis was performed using the FunRich database. Subsequently, a protein–protein interaction (PPI) network of DEGs was generated using Search Tool for the Retrieval of Interacting Genes and displayed via Cytoscape software. The PPI network was analyzed by the Molecular Complex Detection app from Cytoscape, and 16 upregulated hub genes were selected. The Oncomine database was used to detect expression patterns of hub genes for validation. Furthermore, the biological pathways of these 16 hub genes were re‐analyzed, and potential interactions between these genes and miRNAs were explored via FunRich.
Results
A total of 384 DEGs were identified. A Venn diagram determined 88 common DEGs. The PPI network was constructed with 48 nodes and 221 protein pairs. Among them, 16 hub genes were extracted, 14 of which were upregulated in SCLC samples, as compared with normal lung specimens, and 10 were correlated with the cell cycle pathway. Furthermore, 57 target miRNAs for 8 hub genes were identified, among which 31 miRNAs were correlated with the progression of carcinoma, drug‐resistance, radio‐sensitivity, or autophagy in lung cancer.
Conclusion
This study provided effective biomarkers and novel therapeutic targets for diagnosis and prognosis of SCLC and LCNEC.
Common and distinct features of DEGs of SCLC and LCNEC were identified by integrated bioinformatics methods. Genes related to the cell cycle pathway were discussed. Target miRNAs for hub genes were identified and discussed.
Abstract Stability under high‐temperature environments is crucial for amylase to function in starch‐based industries. This study develops a method of modifying protein surfaces by combining ...computer‐aided tools including FoldX, PoPMuSiC, Discovery Studio, and I‐Mutant 2.0 with conserved sequence analysis. A truncated α‐amylase ∆Amy PTG from Parageobacillus thermoglucosidasius DSMZ 2542 is rationally designed through this method to improve its thermostability. Seven single‐site variants are constructed and five of them displayed enhanced thermostability. Next, three double‐site variants are constructed with one particularly successful double‐site variant N31RT213R, exhibiting a 4.3‐fold longer half‐life at 80 °C. Notably, the specific activity of N31RT213R reaches 10 567.16 U mg −1 , higher than ∆Amy PTG (6645.43 U mg −1 ). When applied to the corn starch liquefaction reaction, the mutant N31RT213R gets a higher yield of product concentration of about 255.70 µg mL −1 , compared to 190.72 µg mL −1 for ∆Amy PTG . Intramolecular forces analysis and surface electrostatic charges analysis are conducted to determine possible causes for the improvement. Also, molecular dynamics simulation is used to analyze the flexibility shifts of the entire protein. This innovative rational engineering approach has proven to be a successful strategy for the selection of hot spots for protein thermostability evolution and has the potential to be applied to other enzymes.
α-Amylase (EC 3.2.1.1) from
(generally recognized as safe) exhibited thermal inactivation, hampering its further application in starch-based industries. To address this, we performed structural ...analyses based on molecular dynamics targeting the flexible regions of α-amylase. Subsequently, we rationally designed a thermostable mutant, AmyS1, by introducing disulfide bonds to stabilize the flexible regions. AmyS1 showed excellent thermostability without any stability-activity trade-off, giving a 40-fold longer
(1359 min) at 90 °C. Thermostability mechanism analysis revealed that the introduction of disulfide bonds in AmyS1 refined weak spots and reconfigured the protein's force network. Moreover, AmyS1 exhibited improved pH compatibility and enhanced corn starch liquefaction at 100 °C with a 5.1-fold increased product concentration. Baking tests confirmed that AmyS1 enhanced bread quality and extended the shelf life. Therefore, mutant AmyS1 is a robust candidate for the starch-based industry.
The utilization of metal-organic frameworks (MOFs) as photocatalysts for the degradation of organic pollutants has gained significant attention in recent years, yet the challenge of recycling MOFs ...has hindered their widespread use. In this study, we have fabricated a novel MIL-101(Fe)/Polysulfone (MP) composite hollow microsphere via a Pickering emulsion template approach for the application in photo-Fenton degradation of methylene Blue (MB). Our results revealed that the loading of MIL-101(Fe) plays a crucial role in determining the porosity, density, and optical properties of the MP composite microspheres. The MP composite microspheres exhibited excellent MB removal performance and showed a higher adsorption rate compared to MIL-101(Fe) and Polysulfone (PSF). The enhanced performance can be attributed to the porous structure and electrostatic attraction between MB+ and negatively charged PSF materials. Additionally, the MP composite microspheres displayed good degradation efficiency and a high degree of reusability, remaining stable even after 5 cycles. These results demonstrate that the MP composite microsphere is a highly effective, reusable, and durable photocatalyst for the treatment of water and organic pollutants.
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•Processing composite hollow microspheres via a Pickering emulsion template.•MIL-101(Fe) as particle stabilizer adsorbed on the surface of PSF microspheres.•The degradation efficiency of MB remained at the initial high level after 5 cycles.
Starch-based industries require a robust alpha-amylase capable of withstanding elevated temperatures and long incubation periods. In this study, a loop-grafting strategy based on a computer-aided ...design was proposed to engineer a thermostable alpha-amylase from Geobacillus stearothermophilus. Molecular dynamics (MD) simulations and trajectory analyses were employed to target the weak spots responsible for thermal inactivation, and three loop regions were identified as weak spots requiring improvement. Subsequently, substitute candidates from the thermophilic orthologous library were selected to refine these weak spots and the most promising mutant was screened using thermal unfolding and MD simulations. Expectedly, an alpha-amylase variant was constructed efficiently and specifically, which can withstand high-temperatures up to 100 °C without any stability-activity trade-off, giving an 8.0-fold longer half-life at 100 °C. Notably, the variant exhibited excellent thermotolerance during corn starch liquefaction at 100 °C, giving a 3.3-fold increased product concentration. Furthermore, the origin of the enhanced thermostability based on the dynamic trajectory of the variant was revealed. Successful attempts to tailor the thermal resistance and catalytic activity of alpha-amylase can further fuel the food industry, particularly high-temperature starch-based industries.
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•Loop-grafting based on the computer-aided design produced thermostable alpha-amylase.•Mutant had an 8.0-fold longer half-life at 100 °C with improved catalysis.•This strategy targeted mutation accurately without onerous screening.•The mutant is promising in starch-processing as it enhanced corn starch hydrolysis by 3.3-fold.
We aim to develop and validate an effective nomogram prognostic model for patients with typical lung carcinoid tumors using a large patient cohort from the Surveillance, Epidemiology, and End Results ...(SEER) database.
Data from patients with typical lung carcinoid tumors between 2010 and 2015 were selected from the SEER database for retrospective analysis. Univariate and multivariate Cox analysis was performed to clarify independent prognostic factors. Next, a nomogram was formulated to predict the probability of 3- and 5-year overall survival (OS). Concordance indexes (c-index), receiver operating characteristic analysis and calibration curves were used to evaluate the model.
The selected patients were randomly divided into a training and a validation cohort. A nomogram was established based on the training cohort. Cox analysis results indicated that age, sex, T stage, N stage, surgery, and bone metastasis were independent variables for OS. All these factors, except surgery, were included in the nomogram model for predicting 3- and 5-year OS. The internally and externally validated c-indexes were 0.787 and 0.817, respectively. For the 3-year survival prediction, receiver operating characteristic analysis showed that the areas under the curve in the training and validation cohorts were 0.824 and 0.795, respectively. For the 5-year survival prediction, the area under the curve in the training and validation cohorts were 0.812 and 0.787, respectively. The calibration plots for probability of survival were in good agreement.
The nomogram brings us closer to personalized medicine and the maximization of predictive accuracy in the prediction of OS in patients with typical lung carcinoid tumors.
Circular RNAs (circRNAs) have been implicated in cancer development. However, their regulation, function, and underlying mechanisms of action remain unclear. We found that circHIPK2 was downregulated ...in colon cancer, and low expression levels of circHIPK2 were associated with high tumor grade and poor patient survival. The expression of circHIPK2 was observed to be regulated by the transcription factor HOXD10, which was downregulated in colon cancer. Consequently, low circHIPK2 expression promoted colon cancer cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, circHIPK2 sponges miR-373-3p to upregulate the expression of the tumor suppressor RGMA, leading to the activation of BMP/Smad signaling and, ultimately, the inhibition of colon cancer cells, indicating that circHIPK2 inhibits colon cancer cells through the miR-373-3p/RGMA/BMP pathway. These findings revealed a previously unknown regulation, function, and underlying mechanism of circHIPK2 in cancer cells. Hence, circHIPK2 may have a prognostic value and serve as a potential target for colon cancer treatment.
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•CircHIPK2 functions as a suppressor of colon cancers.•CircHIPK2 inhibits colon cancer cells through miR-373-3p/RGMA/BMP axis.•Downregulation of circHIPK2 is associated with high tumor grade and poor patients' survival.
9,9-Dimethyl-9,10-dihydroacridine (DMAC) and naphthalene are fused to produce a chromophore 12,12-Dimethyl-7,12-dihydrobenzoa acridine (DMBA). Based on DMBA, two emitters, ...12,12-dimethyl-7-phenyl-7,12-dihydrobenzoaacridine (BACH) and 3-fluoro-12,12-dimethyl-7-phenyl-7,12-dihydrobenzoaacridine (BACF), were designed and synthesized. Thanks to the planar structure and weak electron donating ability of DMBA, these two emitters exhibit deep-blue emissions with photoluminescence (PL) spectra peaks (λPLs) of 402–422 nm in solutions and doped films. The non-doped devices based on BACH and BACF present excellent deep-blue electroluminescence (EL) emission with spectra peaks (λELs) of 428 and 427 nm, maximum external quantum efficiencies (EQEs) of 6.09% and 5.99%, respectively. Notably, the CIE coordinates of these non-doped devices closely approach the Rec.2020 standard (0.131, 0.046).
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•A new deep-blue chromophore 12,12-Dimethyl-7,12-dihydrobenzoa acridine (DMBA) were designed with fusion of 9,9-Dimethyl-9,10-dihydroacridine (DMAC) and naphthalene.•Two deep-blue emitters (BACH and BACF) were designed and synthesized based on DMBA.•The photophysical and electroluminance properties of BACH and BACF were characterized and analyzed.•The non-doped devices of BACH and BACF exhibited deep-blue emission and high external quantum efficiencies (∼6%).
Clear cell renal cell carcinoma (ccRCC) is a common malignancy of the genitourinary system and is associated with high mortality rates. However, the molecular mechanism of ccRCC pathogenesis is still ...unclear, which translates to few effective diagnostic and prognostic biomarkers. In this study, we conducted a bioinformatics analysis on three Gene Expression Omnibus datasets and identified 437 differentially expressed genes (DEGs) related to ccRCC development and prognosis, of which 311 and 126 genes are respectively down-regulated and up-regulated. The protein-protein interaction network of these DEGs consists of 395 nodes and 1872 interactions and 2 prominent modules. The Staphylococcus aureus infection and complement and coagulation cascades are significantly enriched in module 1 and are likely involved in ccRCC progression. Forty-two hub genes were screened, of which von Willebrand factor, TIMP metallopeptidase inhibitor 1, plasminogen, formimidoyltransferase cyclodeaminase, solute carrier family 34 member 1, hydroxyacid oxidase 2, alanine-glyoxylate aminotransferase 2, phosphoenolpyruvate carboxykinase 1, and 3-hydroxy-3-methylglutaryl-CoA synthase 2 are possibly related to the prognosis of ccRCC. The differential expression of all nine genes was confirmed by quantitative real-time polymerase chain reaction analysis of the ccRCC and normal renal tissues. These key genes are potential biomarkers for the diagnosis and prognosis of ccRCC and warrant further investigation.
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