Screening of potential targets and small-molecule drugs related to lipid metabolism in ovarian cancer based on bioinformatics.

BACKGROUND: about 70 % of ovarian cancer (OC) patients with postoperative chemotherapy relapse within 2-3 years due to drug resistance and metastasis, and the 5-year survival rate is only about 30 %. Lipid metabolism plays an important role in OC. We try to explore the potential targets and drugs related to lipid metabolism to provide clues for the treatment of OC. METHODS: the gene expression profiles of OC and normal ovarian tissue samples were obtained from the cancer genome atlas (TCGA) and genotype-tissue expression databases (GTEx). The differentially expressed genes (DEGs) were analyzed. Lipid metabolism related genes (LMRGs) were downloaded from MSigDB database. The DEGs related to lipid metabolism in OC was obtained by intersection. And gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses were performed. The protein-protein interaction (PPI) network of lipid metabolism related DEGs was constructed, and seven algorithms were used to screen core potential target genes. Its expression in OC and prognostic ability were analyzed by Univariate Cox. Cmap database mining OC lipid metabolism related potential small-molecular drugs and docking. CCK8, scratch assay, transwell test and free fatty acid (FFA) assay, fluorescence detection of cellular fatty acid uptake, and the reactivity assay of CPT1A were used to detect the biological effects of drugs on OC cell.Rreverse transcription PCR(RT-qPCR) and WesternBlot were performed to measure the expression of core targets. RESULTS: 437 DEGs related to lipid metabolism of OC were screened. GO and KEGG analysis showed that these DEGs were lipid metabolism, fatty acid metabolism, sphingolipid metabolism, PPAR signal pathway and so on. The PPI network based on lipid metabolism DEGs consists of 301 nodes and 1107 interaction pairs, and 6 core target genes were screened. ROC curve analysis showed that all of the 6 genes could predict the prognosis of OC. Three small molecular drugs Cephaeline, AZD8055 and GSK-1059615 were found by cmap and molecular docking showed that they all had good binding ability to target gene. Cephaeline has the strongest inhibitory effect on SKOV3 cells of OC, and could significantly inhibit cell migration and invasion regulate the mRNA and protein expression of some targets, and inhibit lipid metabolism process in ovarian cancer cells. CONCLUSION: six OC potential genes related to lipid metabolism were identified and verified, which can be used as potential biomarkers and therapeutic targets to evaluate the prognostic risk of OC patients. In addition, three small-molecular drugs that may be effective in the treatment of OC were unearthed, among which Cephaeline has the most potential. We speculate that Cephaeline may target six genes to inhibit progression of OC by affecting lipid metabolism.

Molecular Dynamics Simulation of Dual Nanodroplet Impacts on a Cylindrical Surface.

Droplet impact behavior is ubiquitous in various fields. However, the dynamics and spreading mechanisms of micro- and nanoscale droplet impact on curved surfaces, particularly in the case of multiple droplets, have yet to be fully elucidated. In this study, molecular dynamics (MD) methods are employed to investigate the dynamic evolution of double nanodroplet impact on a nano cylindrical wall. The effects of droplet spacing, initial impact velocity, and wall wettability on droplet impact characteristics are analyzed. The results demonstrate that there are five impact modes of nanoscale double-droplet impacts with nanocylinders: spreading-partial wrapping-splitting-complete detachment (SPSC), spreading-complete wrapping-complete attachment (SCC), spreading-partial wrapping-complete attachment (SPC), spreading-partial wrapping-partial attachment (SPP), and spreading-partial wrapping-fragmentation-partial attachment (SPFP). The droplet spacing has an insignificant effect on the impact modes but affects the droplets' spreading shape in both the axial and radial directions. The initial velocity and wall wettability have significant impacts on the droplet impact modes and liquid film spreading characteristics. As the initial velocity increases, the liquid film's radial and axial spreading distances gradually increase. Under hydrophobic conditions, the spreading of the droplet is dominant in the radial direction, while under hydrophilic conditions, the spreading is dominant in the axial direction. Properly reducing the droplet spacing, increasing the impact velocity, and enhancing the wall hydrophobicity can promote detaching the droplet from the cylindrical wall.

Fast adaptive focusing confocal Raman microscopy for large-area two-dimensional materials.

Large-area two-dimensional (2D) materials possess significant potential in the development of next generation semiconductor due to their unique physicochemical properties. Confocal Raman spectroscopy (CRM), a typical 2D material characterization method, has a limited effective measurement area owing to the restricted focus depth of the system and the less-than-ideal level of the substrate. We propose fast adaptive focusing confocal Raman microscopy (FAFCRM) to realize real-time focusing detection for large-area 2D materials. By observing spot changes on the charge coupled device (CCD) caused by placing an aperture in front of the CCD, the methodology gives a focusing resolution up to 100 nm per 60 µm without axial scanning. A graphene was measured over 25.6 mm × 25.6 mm area on focus through all the scanning. The research results provide new perspectives for non-destructive characterization of 2D materials at the inch level.

Polysaccharides extraction from Ganoderma lucidum using a ternary deep eutectic solvents of choline chloride/guaiacol/lactic acid.

In this study, a purposefully formulated ternary deep eutectic solvents (DESs), consisting of choline chloride, guaiacol, and lactic acid in a molar ratio of 1:1:1, was synthesized for the extraction of polysaccharides from Ganoderma lucidum. The physicochemical properties of the synthesized DESs, including viscosity, density, pH, and hydrogen bonds, were comprehensively examined. Verification of the formation of the ternary DESs was accomplished through Fourier transform infrared and Nuclear magnetic resonance spectroscopies. Subsequently, response surface methodology was applied to optimize crucial parameters for polysaccharide extraction using DESs, resulting in a maximal extraction yield of 94.72 mg/g under the optimized conditions. Cyclic experiments demonstrated the commendable cyclic stability of the DESs, with a recovery rate exceeding 88 %. Furthermore, experiments on monosaccharide composition, molecular weight, and antioxidant activity of the isolated polysaccharides were conducted. Density functional theory was employed to gain insights into the molecular mechanism of polysaccharide extraction by DESs. The findings revealed a triple hydrogen bond interaction and a high binding energy (65.29 kcal/mol) between the DESs and glucose, highlighting their significant contribution to the high extraction effectiveness. This molecular-level understanding underscores the inherent superiority of DESs in the polysaccharide extraction processes, providing valuable insights for future applications in this field.

High spatial resolution of topographic imaging and Raman mapping by differential correlation-confocal Raman microscopy.

Confocal Raman microscopy (CRM) has found applications in many fields as a consequence of being able to measure molecular fingerprints and characterize samples without the need to employ labelling methods. However, limited spatial resolution has limited its application when identification of sub-micron features in materials is important. Here, we propose a differential correlation-confocal Raman microscopy (DCCRM) method to address this. This new method is based on the correlation product method of Raman scattering intensities acquired when the confocal Raman pinhole is placed at different (defocused) positions either side of the focal plane of the Raman collection lens. By using this correlation product, a significant enhancement in the spatial resolution of Raman mapping can be obtained. Compared with conventional CRM, these are 23.1% and 33.1% in the lateral and axial directions, respectively. We illustrate these improvements using in situ topographic imaging and Raman mapping of graphene, carbon nanotube, and silicon carbide samples. This work can potentially contribute to a better understanding of complex nanostructures in non-real time spectroscopic imaging fields.

Betulinic acid increases lifespan and stress resistance via insulin/IGF-1 signaling pathway in Caenorhabditis elegans.

Numerous studies reported that betulinic acid (BA), a natural product extracted from birch bark, exhibited various beneficial effects in vitro. However, its pharmacological activities in aging are rarely understood. In this study, Caenorhabditis elegans was deployed as a whole animal model to investigate the impacts of BA on lifespan and stress resistance. Wild-type C. elegans were fed in the presence or absence of BA and tested for a series of phenotypes, including longevity, mobility, reproductive capacity, pharyngeal pumping, heat stress, and oxidative stress. BA at the optimal dose (50 µg/mL) extended the lifespan, improved the healthspan, and significantly evoked the increased oxidative stress resistance in C. elegans. Incorporating the genetic analysis with different types of longevity mutants, DAF-16, the downstream effector of the Insulin/IGF-1 receptor signaling, was revealed to mediate the protective effects of BA on lifespan and antioxidant activity. Together, these data showcased the potential of BA in promoting healthy aging, which shall facilitate its further development in the food and pharmaceutical industries.

Perspectives on lecithin from egg yolk: Extraction, physicochemical properties, modification, and applications.

Egg yolk lecithin has physiological activities as an antioxidant, antibacterial, anti-inflammatory, and neurologic, cardiovascular, and cerebrovascular protectant. There are several methods for extracting egg yolk lecithin, including solvent extraction and supercritical extraction. However, changes in extraction methods and functional activity of egg yolk lecithin are a matter of debate. In this review we summarized the molecular structure, extraction method, and functional activity of egg yolk lecithin to provide a good reference for the development of egg yolk lecithin products in the future.

Recent advances and trends of trichloroethylene biodegradation: A critical review.

Trichloroethylene (TCE) is a ubiquitous chlorinated aliphatic hydrocarbon (CAH) in the environment, which is a Group 1 carcinogen with negative impacts on human health and ecosystems. Based on a series of recent advances, the environmental behavior and biodegradation process on TCE biodegradation need to be reviewed systematically. Four main biodegradation processes leading to TCE biodegradation by isolated bacteria and mixed cultures are anaerobic reductive dechlorination, anaerobic cometabolic reductive dichlorination, aerobic co-metabolism, and aerobic direct oxidation. More attention has been paid to the aerobic co-metabolism of TCE. Laboratory and field studies have demonstrated that bacterial isolates or mixed cultures containing Dehalococcoides or Dehalogenimonas can catalyze reductive dechlorination of TCE to ethene. The mechanisms, pathways, and enzymes of TCE biodegradation were reviewed, and the factors affecting the biodegradation process were discussed. Besides, the research progress on material-mediated enhanced biodegradation technologies of TCE through the combination of zero-valent iron (ZVI) or biochar with microorganisms was introduced. Furthermore, we reviewed the current research on TCE biodegradation in field applications, and finally provided the development prospects of TCE biodegradation based on the existing challenges. We hope that this review will provide guidance and specific recommendations for future studies on CAHs biodegradation in laboratory and field applications.

Unilateral-shift-subtracting confocal microscopy with nanoscale axial focusing precision.

A novel unilateral-shift-subtracting confocal microscopy (USSCM) method with nanoscale axial focusing precision is proposed based on the optical arrangement of conventional confocal microscopy (CM). As the two segments of data on both sides of the confocal axial response curve are very sensitive to variations of the axial position, USSCM introduces an axial shift of S for one segment, to intersect it with the other segment. It then separately interpolates the two segments of intersecting data, subtracts the corresponding interpolated data, and selects the data that exhibit a good linearity from all of the subtracted data to fit a straight line. It calculates the zero position of the fitting line and offsets it by S/2, to precisely reveal the focus position of the confocal system, thereby achieving high-precision imaging of the three-dimensional sample's structure. Theoretical analyses and preliminary experiments indicate that, for excitation wavelength of λ=405 nm, numerical aperture of NA=0.95, and normalized axial shift of S=5.21, USSCM achieves an axial resolution of 3 nm and a repetitive focusing precision of 1.5 nm, while it does not change the lateral resolution of CM. Furthermore, compared with conventional CM, under the same noise condition, USSCM is less affected by system aberration, which leads to higher focusing precision. These findings demonstrate that USSCM is a very efficient method for imaging.

Overexpression of GRK6 attenuates neuropathic pain via suppression of CXCR2 in rat dorsal root ganglion.

G protein-coupled kinase (GRK) 6 is a member of the GRK family that mediates agonist-induced desensitization and signaling of G protein-coupled receptors (GPCRs), thus involving in a wide variety of processes including inflammation and nociception. Recent studies have indicated that chemokines play an important role in chronic pain via increased expression of respective GPCRs. This study was designed to investigate the role of GRK6 and its interaction with substrate chemokine receptors in dorsal root ganglion (DRG) in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Following induction of CCI, GRK6 expression was significantly downregulated in rat DRGs at L4-L6 segments. Overexpression of GRK6 using lentiviral-mediated production strategy via sciatic nerve injection markedly attenuated mechanical allodynia and thermal hyperalgesia in CCI rats. Overexpression of GRK6 also drastically reversed the hyperexcitability of DRG neurons innervating the hind paw and suppressed the enhanced expression of CXCR2 in DRGs of CCI rats. In addition, co-immunoprecipitation, immunofluorescence, and correlation analysis supported the interaction between GRK6 and CXCR2. These results suggest that GRK6 might be a key molecular involved in peripheral mechanism of neuropathic pain and that overexpression of GRK6 might be a potential strategy for treatment for neuropathic pain through inhibition of CXCR2 signal pathway.