Electrochemical detection of nitrofurazone using laser-engraved three-electrode graphene array.

BACKGROUND: Nitrofurazone (NFZ) is a widely-used antimicrobial agent in aquaculture. The NFZ residue can be transmitted to humans through the food chain, and cause adverse health effects including carcinogenesis and teratogenesis. Until now, a number of modified electrodes have been developed for NFZ detection, however, there are some issues that need to be improved. For example, the reported detection sensitivity is relatively low, the modification procedure is complicated, and conventional three-electrode system is used. Therefore, it is quite important to develop new NFZ detection method with higher sensitivity, simplicity and practicality. RESULTS: Herein, a kind of integrated three-electrode array consisted with porous graphene is easily prepared through laser engraving of commercial polyimide tape. Five kinds of graphene arrays were prepared at different laser power percentage (i.e. 30 %, 40 %, 50 %, 60 % and 70 %). It is found that their structure, morphology, fluffiness and porosity show great difference, consequently affecting the electrochemical performance of graphene arrays such as conductivity, active area and electron transfer ability. The engraved graphene array at 50 % laser power percentage (LIG-50 array) is superior owing to uniform 3D structure, abundant pores and high stability. More importantly, LIG-50 array is more active for NFZ oxidation, and significantly enhances the detection sensitivity. The linear range of LIG-50 sensor is from 0.2 to 8 µM, and the detection limit is 0.035 µM, which is successfully used in fish meat samples. SIGNIFICANCE: A sensitive, portable and practical electrochemical sensor has been successfully developed for NFZ using laser-engraved graphene array. The demonstration using fish meat samples manifests this new sensor has good accuracy and great potential in application. This study could provide a new possibility for the design and fabrication of other high-performance electrochemical sensor for various applications in the future.

HydrogelFinder: A Foundation Model for Efficient Self-Assembling Peptide Discovery Guided by Non-Peptidal Small Molecules.

Self-assembling peptides have numerous applications in medicine, food chemistry, and nanotechnology. However, their discovery has traditionally been serendipitous rather than driven by rational design. Here, HydrogelFinder, a foundation model is developed for the rational design of self-assembling peptides from scratch. This model explores the self-assembly properties by molecular structure, leveraging 1,377 self-assembling non-peptidal small molecules to navigate chemical space and improve structural diversity. Utilizing HydrogelFinder, 111 peptide candidates are generated and synthesized 17 peptides, subsequently experimentally validating the self-assembly and biophysical characteristics of nine peptides ranging from 1-10 amino acids-all achieved within a 19-day workflow. Notably, the two de novo-designed self-assembling peptides demonstrated low cytotoxicity and biocompatibility, as confirmed by live/dead assays. This work highlights the capacity of HydrogelFinder to diversify the design of self-assembling peptides through non-peptidal small molecules, offering a powerful toolkit and paradigm for future peptide discovery endeavors.

Interpretable machine learning based on CT-derived extracellular volume fraction to predict pathological grading of hepatocellular carcinoma.

PURPOSE: To develop a non-invasive auxiliary assessment method based on CT-derived extracellular volume (ECV) to predict the pathological grading (PG) of hepatocellular carcinoma (HCC). METHODS: The study retrospectively analyzed 238 patients who underwent HCC resection surgery between January 2013 and April 2023. Six machine learning algorithms were employed to construct predictive models for HCC PG: logistic regression, extreme gradient boosting, Light Gradient Boosting Machine (LightGBM), random forest, adaptive boosting, and Gaussian naive Bayes. Model performance was evaluated using receiver operating characteristic curve analysis, including area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and F1 score. Calibration plots were used for visual evaluation of model calibration. Clinical decision curve analysis was performed to assess potential clinical utility by calculating net benefit. RESULTS: 166 patients from Hospital A were allocated to the training set, while 72 patients from Hospital B (constituting 30.25% of the total sample) were assigned to the test set. The model achieved an AUC of 1.000 (95%CI: 1.000-1.000) in the training set and 0.927 (95%CI: 0.837-0.999) in the validation set, respectively. Ultimately, the model achieved an AUC of 0.909 (95%CI: 0.837-0.980) in the test set, with an accuracy of 0.778, sensitivity of 0.906, specificity of 0.789, negative predictive value of 0.556, and F1 score of 0.908. CONCLUSION: This study successfully developed and validated a non-invasive auxiliary assessment method based on CT-derived ECV to predict the HCC PG, providing important supplementary information for clinical decision-making.

A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy.

METTL3, a primary methyltransferase catalyzing the RNA N6-methyladenosine (m6A) modification, has been identified as an oncogene in several cancer types and thus nominated as a potentially effective target for therapeutic inhibition. However, current options using this strategy are limited. In this study, we targeted protein-protein interactions at the METTL3-METTL14 binding interface to inhibit complex formation and subsequent catalysis of the RNA m6A modification. Among candidate peptides, RM3 exhibited the highest anti-cancer potency, inhibiting METTL3 activity while also facilitating its proteasomal degradation. We then designed a stapled peptide inhibitor (RSM3) with enhanced peptide stability and formation of the α-helical secondary structure required for METTL3 interaction. Functional and transcriptomic analysis in vivo indicated that RSM3 induced upregulation of programmed cell death-related genes while inhibiting cancer-promoting signals. Furthermore, tumor growth was significantly suppressed while apoptosis was enhanced upon RSM3 treatment, accompanied by increased METTL3 degradation, and reduced global RNA methylation levels in two in vivo tumor models. This peptide inhibitor thus exploits a mechanism distinct from other small-molecule competitive inhibitors to inhibit oncogenic METTL3 activity. Our findings collectively highlight the potential of targeting METTL3 in cancer therapies through peptide-based inhibition of complex formation and proteolytic degradation.

Engeletin alleviates depressive-like behaviours by modulating microglial polarization via the LCN2/CXCL10 signalling pathway.

Microglial polarization and associated inflammatory activity are the key mediators of depression pathogenesis. The natural Smilax glabra rhizomilax derivative engeletin has been reported to exhibit robust anti-inflammatory activity, but no studies to date have examined the mechanisms through which it can treat depressive symptoms. We showed that treatment for 21 days with engeletin significantly alleviated depressive-like behaviours in chronic stress social defeat stress (CSDS) model mice. T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) imaging revealed no significant differences between groups, but the bilateral prefrontal cortex of CSDS mice exhibited significant increases in apparent diffusion coefficient and T2 values relative to normal control mice, with a corresponding reduction in fractional anisotropy, while engeletin reversed all of these changes. CSDS resulted in higher levels of IL-1ß, IL-6, and TNF-a production, enhanced microglial activation, and greater M1 polarization with a concomitant decrease in M2 polarization in the mPFC, whereas engeletin treatment effectively abrogated these CSDS-related pathological changes. Engeletin was further found to suppress the LCN2/C-X-C motif chemokine ligand 10 (CXCL10) signalling axis such that adeno-associated virus-induced LCN2 overexpression ablated the antidepressant effects of engeletin and reversed its beneficial effects on the M1/M2 polarization of microglia. In conclusion, engeletin can alleviate CSDS-induced depressive-like behaviours by regulating the LCN2/CXCL10 pathway and thereby altering the polarization of microglia. These data suggest that the antidepressant effects of engeletin are correlated with the polarization of microglia, highlighting a potential avenue for future design of antidepressant strategies that specifically target the microglia.

The pathogenesis of liver cancer and the therapeutic potential of bioactive substances.

Liver cancer is the third most common cause of cancer-related deaths in the world and has become an urgent problem for global public health. Bioactive substances are widely used for the treatment of liver cancer due to their widespread availability and reduced side effects. This review summarizes the main pathogenic factors involved in the development of liver cancer, including metabolic fatty liver disease, viral infection, and alcoholic cirrhosis, and focuses on the mechanism of action of bioactive components such as polysaccharides, alkaloids, phenols, peptides, and active bacteria/fungi. In addition, we also summarize transformation methods, combined therapy and modification of bioactive substances to improve the treatment efficiency against liver cancer, highlighting new ideas in this field.

Efficacy of MR diffusion kurtosis imaging for differentiating low-grade from high-grade glioma before surgery: A systematic review and meta-analysis.

BACKGROUND: Accurate discrimination and diagnosis of low-grade glioma (LGG) and high-grade glioma (HGG) before surgery is clinically important because it affects the patient's outcome and guides the clinicians to select appropriate management. The aim of this study was to evaluate the diagnostic performance of diffusion kurtosis imaging (DKI) for differentiating LGG from HGG. METHODS: A literature search of the PubMed, Web of Science, Cochrane Library and EMBASE databases was conducted up to December 15, 2020. Studies that evaluated the diagnostic performance of DKI for differentiating LGG from HGG were selected. Retrieved hits were evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Summary sensitivity and specificity were determined, and the data analysis was performed using Stata 14.0 and Review Manager 5.3. RESULTS: Thirteen studies with 705 patients were included. The individual sensitivity and specificity of the 13 studies varied from 71% to 100% for sensitivity and 73-100% for specificity. The pooled sensitivity of DKI was 88% (95% confidence interval [CI], 83-91%), and the pooled specificity was 91% (95% CI, 86-95%). The area under the summary receiver operating characteristic curve was 0.93 (95% CI, 0.90-0.95). The pooled diagnostic odds ratio of DKI was 64.85 (95% CI 38.52-109.19). The levels of heterogeneity for sensitivity and specificity across the included studies were high (I2 =66%) and mild (I2 =47.04%), respectively. The multiple subgroup analyses were driven by DKI technique and study region. CONCLUSIONS: DKI demonstrated a high diagnostic performance for differentiation of LGG from HGG.

The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review.

Chlorogenic acid (CGA), also known as coffee tannic acid and 3-caffeoylquinic acid, is a water-soluble polyphenolic phenylacrylate compound produced by plants through the shikimic acid pathway during aerobic respiration. CGA is widely found in higher dicotyledonous plants, ferns, and many Chinese medicine plants, which enjoy the reputation of "plant gold." We have summarized the biological activities of CGA, which are mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system, and action on blood vessels. We further determined the main applications of CGA in the food industry, including food additives, food storage, food composition modification, food packaging materials, functional food materials, and prebiotics. With a view to the theoretical improvement of CGA, biological activity mechanism, and subsequent development and utilization provide reference and scientific basis.

The bioactivity and applications of pomegranate peel extract: A review.

Pomegranate peel (PP) is a by-product in the processing of pomegranate products, which is usually discarded as a waste. However, a large number of researches have shown that pomegranate peel extract (PPE) is rich in a variety of phenolic substances, among which ellagic acid (EA), as one of the main active components, has significant biological activities, such as anti-oxidation, anti-tumor, anti-inflammatory, neuroprotection, anti-viral, and anti-bacterial. We analyzed the mechanism of EA's biological activity, and discussed its application in the food industry, for instance, food preservation, food additives, and functional foods. Combined with the research status of PPE, we discussed the limitations and development potential of PPE, in order to provide theoretical reference and scientific basis for the development and utilization of pomegranate by-products. PRACTICAL APPLICATIONS: Pomegranate peel (PP), the inedible part of the fruit, is usually treated as waste. In recent years, researchers have been committed to exploring various bioactive ingredients in PP and exploring its potential benefits to human health, which has far-reaching significance. In this paper, the chemical constituents of polyphenols in PP were reviewed, mainly focusing on the biological activity and mechanism of ellagic acid (EA). We reviewed the applications and invention patents of pomegranate peel extract (PPE) in food field, including food preservation, food additive, and functional foods, providing reference for the recycling and reuse of PP.

Identification of Differentially Expressed Genes and Signaling Pathways in Glioma by Integrated Bioinformatics Analysis.

BACKGROUND: Gene alterations are very vital when it comes to the molecular pathogenesis of glioma. In this study, there was the design of the probable candidate genes in the glioma. METHODS: Gene Expression Omnibus (GEO) database data sets of glioma tissue were retrieved and the differentially expressed genes (DEGs) from the individual microarray were merged. The following were performed: Gene Ontology; enrichment analysis; Kyoto Encyclopedia of Genes and Genomes (KEGG); pathway analysis; protein-protein interaction networks analysis. RESULTS: The following were selected: 4 GEO data sets that included 370 high-grade glioma samples as well as 169 low-grade glioma samples. Identification of a total of 174 DEGs was done. Out of the identified DEGs, 82 were upregulated and 92 were downregulated genes. According to the Gene Ontology analysis, the primary biologic focus of DEGs included passive transmembrane transporter activity, regulation of channel activity, as well as the revelation that the biologic roles of DEGs aimed primarily on regulating channel activity, as well as the monovalent inorganic cation transmembrane transporter activity. The most significant pathway in KEGG analysis was PI3K-AKT signaling pathway. Some of the significant hub genes as per the protein-protein interaction network analysis included CDC20, NDC80, DLGAP5, CENPF, CENPE, ASPM, TPX2, TOP2A, RRM2, and PRC1. CONCLUSION: From this study, it is evidenced that the use of integrated bioinformatics analyses in screening for pathways and DEGs in glioma can help us understand the clinical significance of understanding glioma, the molecular mechanism that underlies the development of glioma, as well as the provision of an effective target to treat glioma.

Can dynamic contrast-enhanced MRI evaluate VEGF expression in brain glioma? An MRI-guided stereotactic biopsy study.

PURPOSE: To investigate whether pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to evaluate vascular endothelial growth factor (VEGF) expression in brain glioma based on a point-to-point basis. MATERIALS AND METHODS: Forty-seven patients with treatment-naïve glioma received preoperative DCE-MRI before stereotactic biopsy. We histologically quantified VEGF from section of stereotactic biopsies, and co-registered biopsy locations with localized measurements of DCE-MRI parameters including volume transfer coefficient (Ktrans), reverse reflux rate constant (Kep), extracellular extravascular volume fraction (Ve) and blood plasma volume (Vp). The correlations between DCE-MRI parameters (Ktrans, Kep, Ve and Vp) and VEGF were determined using Spearman correlation coefficient. P≤.05 was considered statistically significant. RESULTS: Seventy-nine biopsy samples were obtained and graded into 45 high-grade gliomas (HGGs) and 34 low-grade gliomas (LGGs). Ktrans showed a significant positive correlation with VEGF expression in HGGs group (ρ=0.505, P<0.001) and in combined group (LGGs+HGGs) (ρ=0.549, P<0.001), but not in LGGs group (P>0.05). Kep, Ve or Vp was not correlated with VEGF even though a positive trend showed (P>0.05). CONCLUSIONS: DCE-MRI is a useful, non-invasive imaging technique for quantitative evaluation of VEGF, and its parameter Ktrans other than Kep, Ve or Vp may be used as a surrogate for VEGF expression in brain gliomas.

Quantitative Proteomics of TRAMP Mice Combined with Bioinformatics Analysis Reveals That PDGF-B Regulatory Network Plays a Key Role in Prostate Cancer Progression.

Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice is a widely used transgenic animal model of prostate cancer (PCa). We performed a label-free quantitative proteomics analysis combined with a bioinformatics analysis on the entire prostate protein extraction from TRAMP mice and compared it with WT littermates. From 2379 total identified proteins, we presented a modest mice prostate reference proteome containing 919 proteins. 61 proteins presented a significant expression difference between two groups. The integrative bioinformatics analysis predicted the overexpression of platelet-derived growth factor B (PDGF-B) in tumor tissues and supports the hypothesis of the PDGF-B signaling network as a key upstream regulator in PCa progression. Furthermore, we demonstrated that Crenolanib, a novel PDGF receptor inhibitor, inhibited PCa cell proliferation in a dose-dependent manner. Finally, we revealed the importance of PDGF-B regulatory network in PCa progression, which will assist us in understanding the role and mechanisms of PDGF-B in promoting cancer growth and provide valuable knowledge for future research on anti-PDGF therapy.

Evaluation of computed tomography vascular reconstruction for the localization diagnosis of perigastric mass.

BACKGROUND: The aim of this study was to evaluate the utility of computed tomography (CT) vascular reconstruction in the localization diagnosis of perigastric mass. METHODS: Fifty-eight patients with pathologically detected perigastric mass underwent abdominal dynamic contrast-enhanced CT. CT vascular reconstructions were produced from arterial phase data using volume rendering (VR), multiplanar reconstruction (MPR), and maximal intensity projection (MIP). Image analysis was focused on the relationship between the mass, perigastric arteries, and the gastric wall. Localization diagnosis values were compared between CT vascular reconstruction and dynamic-enhanced CT images. RESULTS: Among the 58 cases of perigastric mass, 41 cases originated from the stomach, 7 cases from the left liver lobe, 6 from the pancreas, 2 from lessor omental bursa, 1 from transverse mesocolon, and 1 from left adrenal gland. The accuracy of CT vascular reconstruction images in the localization diagnosis of perigastric mass was higher than that of dynamic-enhanced CT images (98.3% and 86.2%, respectively, P = .04). On the reference level, 35 (35/41) patients with stomach-originated masses showed the mass adjacent perigastric arteries pushed away from the stomach (arterial displacement sign), and 15 (15/17) patients with nonstomach-originated masses showed perigastric arteries between the mass and the stomach (arterial entrapment sign). The sensitivity, specificity, positive predictive value, and negative predictive value of the localization diagnosis of perigastric mass with arterial displacement sign were 85.4%, 100%, 100%, and 73.9%, respectively, and with arterial entrapment sign, 88.2%, 100%, 100%, and 95.3%, respectively. CONCLUSION: CT vascular reconstruction can clearly depict the relationship between perigastric mass and adjacent perigastric arteries, which may help us more accurately differentiate between stomach-originated and nonstomach-originated masses compared with original dynamic-enhanced CT images.

Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins in platelet-derived growth factor b signaling pathway.

Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues. Notably, several significant proteins are in the PDGF-B signaling pathway, including peroxiredoxin5 (PRDX5), S100A6, calreticulin (CALR) and cathepsin D (CTSD), which were validated by western blot. Furthermore, upstream regulators including PDGF-B, PDGFR-ß, Akt, eIF4E and p70s6K were found significantly increased in the gastric cancer tissues. In addition, silencing of PRDX5 and PDGF-B suppressed the proliferation of gastric cancer cells in vitro. The administration of exogenous PDGF-BB recovered the reduced expression of PDGF-B signaling pathway in PDGF-B knockdown cells. Taken together, our findings suggested that PDGF-B signaling pathway plays an important role in the regulation of gastric cancer proliferation and the inhibition of this pathway may be a potential approach for treatment of gastric cancer.

MicroRNA-205 suppresses the invasion and epithelial-mesenchymal transition of human gastric cancer cells.

Distant metastasis is the predominant pattern of gastric cancer (GC) recurrence, and is the most common cause of cancer­associated mortality. Accumulating evidence has suggested that aberrant activation of epithelial­mesenchymal transition has a crucial role in the genesis, invasion and metastasis of various types of cancer, including GC. Using Cell Counting kit­8 and Transwell assays, the effects of microRNA (miR)­205 on the proliferation, migration and invasion of NCI­H87 GC cells were determined, and the potential underlying mechanisms were explored. The results of the present study demonstrated that miR­205, which has been reported to function as a tumor suppressor in various types of cancer, significantly suppressed the migration and invasion of GC cells, which may be correlated with its suppressive effects on EMT. Upon transfection with miR­205, the epithelial marker CDH1 (E­cadherin) was upregulated, and the mesenchymal markers CDH2 (N­cadherin) and vimentin were suppressed. Furthermore, zinc­finger E­box­binding homeobox factor­1 (ZEB1) was identified as a putative target gene of miR­205 in GC, which may be associated with its suppressive effects. The results of the present study may provide novel diagnostic and therapeutic options for the treatment of human GC.

Evaluating the effect of high-intensity focused ultrasound therapy on liver tumors using multislice CT perfusion.

The aim of this study was to investigate the changes of the multislice computed tomography (MSCT) perfusion parameters and histopathology of the liver in rabbits with VX2 tumors before and after high-intensity focused ultrasound (HIFU) therapy. VX2 carcinoma cells were implanted into the livers of eight New Zealand white rabbits 3 weeks prior to the treatment. MSCT perfusion was performed one week before and one and six weeks after the treatment. These CT perfusion (CTP) data, including hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT) and permeability-surface area product (PS), were analyzed semi-quantitatively and qualitatively. Furthermore, the histopathological features of the liver tissues were also assessed semi-quantitatively before and after the treatment. Six weeks after HIFU therapy, MTT increased noticeably from 5.45±0.27 to 10.38±2.22 sec (P<0.05) and PS decreased significantly from 79.03±3.41 to 68.13±0.21 ml/100 g/min (P<0.05), while no significant differences in HBF and HBV were found. Furthermore, more CD3(+) T cells were observed at the rim and center of the liver tumors six weeks after treatment. Therefore, HIFU therapy may be a simple and effective method for the treatment of liver tumors. CTP, as an effective method to obtain functional information about HBF, is able to quantify tumor vascularity and angiogenesis in liver tumors.