Identification of peanut skin components for treating hepatocellular carcinoma via network pharmacology and in vitro experiments.

Peanut skin (PS) contains various flavonoids and phenols that have antitumor and antioxidant effects. However, no research has been conducted on PS and hepatocellular carcinoma (HCC). Therefore, this study sought to explore the potential mechanism of PS in treating HCC. PS was searched for in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SYMMAP databases. HCC targets were searched for in five major databases. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Molecular docking and molecular dynamics simulation were used for verification. Furthermore, in vitro experiments were used to verify the regulation of PS on human HCC (HepG2) cells. Ten ingredients and 95 common targets were identified for PS and HCC, respectively. The key targets of ingredients mainly relate to pathways such as hepatitis B, lipid and atherosclerosis, advanced glycation end products (AGEs)-AGE receptors (RAGEs) signaling pathway in diabetic complications, interleukin-17 (IL-17) signaling pathway, mitogen activated kinase-like protein (MAPK) signaling pathway, the PI3K-Akt signaling pathway. In addition, the molecular docking and molecular dynamics simulation analysis indicated the ingredients had strong binding ability with the targets. Moreover, in vitro experiments confirmed that luteolin can promote the apoptosis of HepG2 cells by controlling the expression of phosphorylated protein-tyrosine kinase (p-AKT). This study provides preliminary evidence that PS produces a marked effect in regulating multiple signaling pathways in HCC through multiple ingredients acting on multiple core genes, including AKT serine/threonine kinase 1 (AKT1), MYC, caspase 3 (CASP3), estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), jun proto-oncogene(JUN), and provides the basis for follow-up research to verify the mechanism of action of PS in treating HCC.

The Application of Artificial Intelligence in Thyroid Nodules: A Systematic Review Based on Bibliometric Analysis.

BACKGROUND: Thyroid nodules are common lesions in benign and malignant thyroid diseases. More and more studies have been conducted on the feasibility of artificial intelligence (AI) in the detection, diagnosis, and evaluation of thyroid nodules. The aim of this study was to use bibliometric methods to analyze and predict the hot spots and frontiers of AI in thyroid nodules. METHODS: Articles on the application of artificial intelligence in thyroid nodules were retrieved from the Web of Science core collection database. A website (https://bibliometric.com/), VOSviewer and CiteSpace software were used for bibliometric analyses. The collaboration maps of countries and institutions were analyzed. The cluster and timeline view based on cocitation references and keywords citation bursts visualization map were generated. RESULTS: The study included 601 papers about AI in thyroid nodules. China contributed to more than half (52.41%) of these publications. The cluster view and timeline view of co-citation references were assembled into 9 clusters, "AI", "deep learning", "papillary thyroid carcinoma", "radiomics", "ultrasound image", "biomarkers", "medical image segmentation", "central lymph node metastasis (CLNM)", and "self-organizing auto-encoder". The "AI", "radiomics", "medical image segmentation", "deep learning," and "CLNM", emerging in the last 10 years and continuing until recent years, were included. CONCLUSION: An increasing number of scholars were devoted to this field. The potential future research hotspots include risk factor assessment and CLNM prediction of thyroid carcinoma based on radiomics and deep learning, automatic segmentation based on medical images (especially ultrasound images).

Stereoselective synthesis of (R)-(+)-1-(1-naphthyl)ethylamine by ω-amine transaminase immobilized on amino modified multi-walled carbon nanotubes and biocatalyst recycling.

Immobilized enzymes exhibit favorable advantages in biocatalysis, such as high operation stability, feasible reusability, and improved organic solvents tolerance. Herein, an immobilized ω-amine transaminase AtATA@MWCNTs-NH2 is successfully prepared using amino modified multi-walled carbon nanotubes as carrier and glutaraldehyde as crosslinker. Under the optimum immobilization conditions, the activity recovery is 78.7%. Compared with purified enzyme AtATA, AtATA@MWCNTs-NH2 possesses superior stability, even in harsh conditions (e.g., high temperature, acidic or alkali environment, and different kind of organic solvents). To simplify the separation and extraction of products, we choose methanol (10%, v/v) as the cosolvent, replacing DMSO (20%, v/v) in our previous work, for the catalytic reaction of AtATA@MWCNTs-NH2. AtATA@MWCNTs-NH2 can be used for stereoselective synthesis (R)-(+)- 1(1-naphthyl)ethylamine ((R)-NEA) for 15 cycles, with the e.e.p (enantiomeric excess) > 99.5%. The catalytic process of AtATA@MWCNTs-NH2 achieves cycle production of (R)-NEA using methanol as cosolvent.

The value of radiomics-based CT combined with machine learning in the diagnosis of occult vertebral fractures.

PURPOSE: To develop and evaluate the performance of radiomics-based computed tomography (CT) combined with machine learning algorithms in detecting occult vertebral fractures (OVFs). MATERIALS AND METHODS: 128 vertebrae including 64 with OVF confirmed by magnetic resonance imaging and 64 corresponding control vertebrae from 57 patients who underwent chest/abdominal CT scans, were included. The CT radiomics features on mid-axial and mid-sagittal plane of each vertebra were extracted. The fractured and normal vertebrae were randomly divided into training set and validation set at a ratio of 8:2. Pearson correlation analyses and least absolute shrinkage and selection operator were used for selecting sagittal and axial features, respectively. Three machine-learning algorithms were used to construct the radiomics models based on the residual features. Receiver operating characteristic (ROC) analysis was used to verify the performance of model. RESULTS: For mid-axial CT imaging, 6 radiomics parameters were obtained and used for building the models. The logistic regression (LR) algorithm showed the best performance with area under the ROC curves (AUC) of training and validation sets of 0.682 and 0.775. For mid-sagittal CT imaging, 5 parameters were selected, and LR algorithms showed the best performance with AUC of training and validation sets of 0.832 and 0.882. The LR model based on sagittal CT yielded the best performance, with an accuracy of 0.846, sensitivity of 0.846, and specificity of 0.846. CONCLUSION: Machine learning based on CT radiomics features allows for the detection of OVFs, especially the LR model based on the radiomics of sagittal imaging, which indicates it is promising to further combine with deep learning to achieve automatic recognition of OVFs to reduce the associated secondary injury.

Prediction of Central Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma by CT Radiomics.

RATIONALE AND OBJECTIVES: To explore the feasibility of the preoperative prediction of pathological central lymph node metastasis (CLNM) status in patients with negative clinical lymph node (cN0) papillary thyroid carcinoma (PTC) using a computed tomography (CT) radiomics signature. MATERIALS AND METHODS: A total of 97 PTC cN0 nodules with CLNM pathology data (pN0, with CLNM, n = 59; pN1, without CLNM, n = 38) in 85 patients were divided into a training set (n = 69) and a validation set (n = 28). For each lesion, 321 radiomic features were extracted from nonenhanced, arterial and venous phase CT images. Minimum redundancy and maximum relevance and the least absolute shrinkage and selection operator were used to find the most important features with which to develop a radiomics signature in the training set. The performance of the radiomics signature was evaluated by receiver operating characteristic curves, calibration curves and decision curve analysis . RESULTS: Three nonzero the least absolute shrinkage and selection operator coefficient features were selected for radiomics signature construction. The radiomics signature for distinguishing the pN0 and pN1 groups achieved areas under the curve of 0.79 (95% CI 0.67, 0.91) in the training set and 0.77 (95% CI 0.55, 0.99) in the validation set. The calibration curves demonstrated good agreement between the radiomics score-predicted probability and the pathological results in the two sets (p= 0.399, p = 0.191). The decision curve analysis curves showed that the model was clinically useful. CONCLUSION: This radiomic signature could be helpful to predict CLNM status in cN0 PTC patients.

Iris metastasis from clear cell renal cell carcinoma: A case report.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common type of tumor that can metastasize to any organs and sites. However, it is extremely rare for ccRCC to metastasize to the iris. Here, we describe a rare case of iris metastasis from ccRCC with a history of left nephrectomy in 2010. CASE SUMMARY: A 62-year-old male was admitted to the hospital due to blurred vision and red eyes, and a mass was found on the iris in the right eye. B-scan ultrasonography revealed a well-bounded high-density lesion at the corner of the anterior chamber at the 3-4 o'clock position. Phacoemulsification with simultaneous intraocular lens implantation and iridocyclectomy was performed in the right eye. The lesion was confirmed to be metastatic ccRCC by histological and immunohistochemical analyses. The patient was still alive at 9 mo after surgical treatment. Ocular metastasis can be an initial sign with a poor prognosis. Timely detection and treatment may improve survival. Clinicians should pay attention to similar metastatic diseases to prevent misdiagnosis leading to missed treatment opportunities. CONCLUSION: This report of the characteristics and successful management of a rare case of iris metastasis from ccRCC highlights the importance of a comprehensive medical history, histopathology, immunohistochemistry, and clinical manifestation for successful disease diagnosis.

Synthesis of 2-arylethenesulfonyl fluorides and isoindolinones: Ru-catalyzed C-H activation of nitrones with ethenesulfonyl fluoride.

A novel strategy for the synthesis of 2-arylethenesulfonyl fluorides from nitrones and ethenesulfonyl fluoride (ESF) by the activation of the C-H bond using an inexpensive and readily available Ru-catalyst has been developed. In this process, the directing group can be concomitantly converted to an amide group. Interestingly, changing the substituent of the nitrogen of nitrones from a tert-butyl to a methyl group resulted in the formation of cyclic isoindolinones. Detailed mechanistic studies are also presented.

Porous Lactose as a Novel Ingredient Carrier for the Improvement of Quercetin Solubility In Vitro.

In this work, quercetin was loaded in the highly-porous lactose via the adsorption of quercetin molecules in ethanol. The method aims to improve the quercetin solubility and the loading capacity of lactose. The method relates to the synthesis of the highly-porous lactose with a particle size of ∼35 µm, a mean pore width of ∼30 nm, a BET surface area of 35.0561 ± 0.4613 m2/g, and a BJH pore volume of ∼0.075346 cc/g. After the quercetin loading in ethanol, BET surface area and BJH pore volume of porous lactose were reduced to 28.8735 ± 0.3526 m2/g and 0.073315 cc/g, respectively. The reduction rate was based on the quercetin loading efficiency of highly-porous lactose. DSC analysis and XRD analysis suggest that the sediments of quercetin in the nanopores of porous lactose are crystalline. FTIR spectroscopy results suggest that there is no significant interaction between quercetin and lactose. The highly-porous lactose had a higher loading efficiency of 20.3% (w/w) compared to the α-lactose (with 5.2% w/w). The release rates of quercetin from the highly-porous lactose tablets were faster compared to the conventional α-lactose carrier.

Synthesis of Indolo[2,1-a]benzazepinones through Rhodium-Catalyzed Cascade Reactions of 2-Arylindoles with Allyl Alcohols.

An efficient synthesis of indolo[2,1-a]benzazepinones through rhodium-catalyzed cascade reactions of 2-arylindoles with allyl alcohols has been developed. This work expands the scope of products that are available through C-H activation/intramolecular annulation reactions of 2-arylindoles in organic synthesis.

Rh(III)-Catalyzed Regioselective Annulations of 3-Arylisoxazolones and 3-Aryl-1,4,2-dioxazol-5-ones with Propargyl Alcohols: Access to 4-Arylisoquinolines and 4-Arylisoquinolones.

The Rh(III)-catalyzed dual directing group assisted C-H activation/annulation of 3-arylisoxazolones with propargyl alcohols has been developed, which expands the application scope of isoxazolones in organic synthesis. This protocol also worked well with 3-aryl-1,4,2-dioxazol-5-ones to produce synthetically and biologically important 4-arylisoquinolones.

CCAAT enhancer binding protein α suppresses proliferation, metastasis, and epithelial-mesenchymal transition of ovarian cancer cells via suppressing the Wnt/ß-catenin signaling.

CCAAT enhancer-binding protein alpha (CEBPA, also known as C/EBPα) is a transcription factor that plays an essential role in regulating terminal differentiation and cell proliferation of many tissues. The objective of this study was to explore the potential function of CEBPA in ovarian cancer. The expression of CEBPA in ovarian cancer samples and adjacent normal tissues was evaluated by qRT-PCR. The putative role of CEBPA in ovarian cancer cells was evaluated by immunohistochemistry, western blot, cell viability assay, BrdU incorporation assay, soft agar colony formation assay, Transwell cell migration and invasion assay, tumor xenograft formation, and lung metastasis model. We found that CEBPA was downregulated in ovarian cancer samples and predicted a poor prognosis. CRISPR/Cas9-mediated CEBPA knockout promoted proliferation, anchorage-independent growth, migration, invasion, and EMT of ovarian cancer cells, while enforced CEPBA expression suppressed proliferation, anchorage-independent growth, migration, invasion, EMT, tumor xenograft growth, and lung metastasis of ovarian cancer cells. Furthermore, we found that the knockout of CEBPA activated Wnt/ß-catenin signaling in ovarian cancer cells, while CEBPA overexpression suppressed Wnt/ß-catenin activation. Our data indicated that CEBPA acted as a tumor suppressor in ovarian cancer, and might be a potential prognostic marker for ovarian cancer treatment.

Metabolic profiling of rats poisoned with paraquat and treated with Xuebijing using a UPLC-QTOF-MS/MS metabolomics approach.

Xuebijing (XBJ) is a compound Chinese medicine that contains Paeoniae Radix Rubra, ChuanXiong Rhizoma, Salvia Miltiorrhiza Radix et Rhizoma, Carthami Flos, and Angelicae Sinensis Radix. It is widely used in China to treat sepsis. Previous studies have demonstrated that XBJ can decrease mortality in patients with moderate paraquat poisoning. However, the mechanism by which it exerts this effect is not completely clear. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-based metabolomics approach was used to perform a metabolic profiling analysis. Principal component analysis (PCA), random forest (RF), and partial least squares discriminant analysis (PLS-DA) were used to identify metabolites to clarify the mechanism of XBJ's activity. XBJ clearly alleviated lung injury in a Sprague Dawley (SD) rat model of paraquat (PQ) poisoning. Seven metabolites related to four pathways, including those involved in sphingolipid and phospholipid metabolism, amino acid metabolism, unsaturated fatty acid metabolism, and pantothenic acid and CoA biosynthesis, were present at different levels in PQ-poisoned rats treated with XBJ compared with untreated rats. XBJ can ameliorate the effects of PQ poisoning in SD rats. Using a metabolomics approach enabled us to gain new insight into the mechanism underlying this effect.

Circularly Polarized Thermally Activated Delayed Fluorescence Emitters in Through-Space Charge Transfer on Asymmetric Spiro Skeletons.

This work describes a strategy to produce circularly polarized thermally activated delayed fluorescence (CP-TADF). A set of two structurally similar organic emitters SFST and SFOT are constructed, whose spiro architectures containing asymmetric donors result in chirality. Upon grafting within the spiro frameworks, the donor and acceptor are fixed proximally in a face-to-face manner. This orientation allows intramolecular through-space charge transfer (TSCT) to occur in both emitters, leading to TADF properties. The donor units in SFST and SFOT have a sulfur and oxygen atom, respectively; such a subtle difference has great impacts on their photophysical, chiroptical, and electroluminescence (EL) properties. SFOT exhibits greatly enhanced EL performance in doped organic light-emitting diodes, with external quantum efficiency (EQE) up to 23.1%, owing to the concurrent manipulation of highly photoluminescent quantum efficiency (PLQY, ∼90%) and high exciton utilization. As a comparison, the relatively larger sulfur atom in SFST introduces heavy atom effects and leads to distortion of the molecular backbone that lengthens the donor-acceptor distance. SFST thus has lower PLQY and faster nonradiative decay rate. The collective consequence is that the EQE value of SFST, i.e., 12.5%, is much lower than that of SFOT. The chirality of these two spiro emitters results in circularly polarized luminescence. Because SFST has a more distorted molecular architecture than SFOT, the luminescence dissymmetry factor (|glum|) of circularly polarized luminescence of one enantiomer of the former, namely, either (S)-SFST or (R)-SFST, is almost twice that of (S)-SFOT/(R)-SFOT. Moreover, the CP organic light-emitting diodes (CP-OLEDs) show obvious circularly polarized electroluminescence (CPEL) signals with gEL of 1.30 × 10-3 and 1.0 × 10-3 for (S)-SFST and (S)-SFOT, respectively.

Retracted: Allopregnanolone restores the tyrosine hydroxylase-positive neurons and motor performance in a 6-OHDA-injected mouse model.

AIMS: It has been reported that allopregnanolone (APα) promotes the neurogenesis of the neural progenitor cells (NPCs) in the subventricular zone (SVZ) and prevents the decrease of dopaminergic neurons in 6-hydroxydopamine (6-OHDA)-treated mice by binding to γ-aminobutyric acid A receptor (GABAAR) and then opening voltage-gated L-type Ca2+ channel, but the underlying mechanisms remain elusive. The aim of this study was to explore the possible involvement of GABAAR and calcium/calmodulin-dependent protein kinase II delta 3 (CaMKIIδ3) in this process. METHODS: 6-OHDA-treated mice and primary cultured midbrain cells were administrated with APα and GABAAR antagonist bicuculline (Bic), and the proliferation and differentiation of NPCs, the tyrosine hydroxylase (TH)-positive neurons and their fibers, the expression levels of CaMKIIδ3 and brain-derived neurotrophic factor (BDNF), and motor functions were measured using ELISA, immunohistochemical staining, real-time RT-PCR, Western blot, and behavioral test. RESULTS: Allopregnanolone significantly promoted the phosphorylation of cytoplasmic CaMKIIδ3 and its nuclear translocation by binding to GABAAR, which, in turn, increased the expression levels of BDNF. This may account for the findings that the exogenous APα enhanced the proliferation and differentiation of NPCs, and ameliorated the nigrostriatal system and behavioral performance in 6-OHDA-treated mice. CONCLUSIONS: Allopregnanolone may directly activate GABAAR, which, in turn, enhance the proliferation and differentiation of NPCs via upregulating the expression levels of CaMKIIδ3, and finally contribute to the restoration of dopaminergic neurons in 6-OHDA-treated mice.

Access to 4-Alkenylated Coumarins via Ruthenium-Catalyzed Olefinic C-H Alkenylation of Coumarins with Modifiable and Removable Directing Groups.

The ruthenium-catalyzed activation of the C4 position of coumarins for coupling with acrylates was described using modifiable ketone as a directing group. The alkenylation reaction provided a direct approach to prepare previously inaccessible 4-alkenylated coumarins with operational simplicity and high atom-economy. This protocol also worked well with coumarin-3-carboxylic acids to unveil a rare instance of a tandem alkenylation/decarboxylation reaction. The potential value of this approach was further highlighted by the efficient synthesis of several heterocyclic fused coumarin derivatives.

Serum Lipid Metabolic Derangement is Associated with Disease Progression During Chronic HBV Infection.

BACKGROUND: To investigate the relationship between serum lipid levels and disease progression during chronic hepatitis B virus infection. METHODS: We selected 73 healthy controls and 163 patients with chronic HBV infection as the study subjects. The chronic HBV infection patients were divided into the HBV carrier group (74 patients), chronic hepatitis B group (71 patients), and liver cirrhosis group (21 patients). The age, gender, body mass index, blood lipid index, liver function index, and HBV DNA levels of all participants were tested and recorded. A t-test or the Mann-Whitney U test was used to compare the data between two groups; data from multiple groups were compared using one-way ANOVA or the Kruskal-Wallis Test. RESULTS: We observed that the serum HDL cholesterol (1.00 ± 0.30 mmol/L in the HBV-infected group, 1.29 ± 0.23 mmol/L in the control group) and APOA (1.29 ± 0.35 mmol/L, 1.36 ± 0.21 mmol/L, respectively) concentrations were significantly lower in the HBV-infected group than in the control group (p < 0.05). As the disease progressed, the blood lipid and lipoprotein values were significantly lower in the cirrhosis group TC (3.26 ± 1.00 mmol/L), HDL cholesterol (0.77 ± 0.33 mmol/L), LDL cholesterol (2.09 ± 0.62 mmol/L), and APOB (0.57 ± 0.18 mmol/L) compared with the control group, the carrier group, and the chronic hepatitis B group (p < 0.05). The serum HBV DNA level was significantly, positively correlated with the blood HDL concentration (carrier group R = 0.340, p = 0.02; chronic hepatitis B group R = 0.329, p = 0.014). There was no correlation between the HBV DNA and lipid levels in patients with cirrhosis. CONCLUSIONS: Serum lipid metabolic derangement was associated with disease progression during chronic HBV infection. Liver function and blood lipid levels were significantly lower in patients with hepatitis B-related cirrhosis.

Management of Exciton for Highly-Efficient Hybrid White Organic Light-Emitting Diodes with a Non-Doped Blue Emissive Layer.

Hybrid white organic light-emitting diodes (WOLEDs) have drawn great attention both for display and solid-state lighting purposes because of the combined advantages of desirable stability of fluorescent dyes and high efficiency of phosphorescent materials. However, in most WOLEDs, obtaining high efficiency often requires complex device structures. Herein, we achieved high-efficiency hybrid WOLEDs using a simple but efficacious structure, which included a non-doped blue emissive layer (EML) to separate the exciton recombination zone from the light emission region. After optimization of the device structure, the WOLEDs showed a maximum power efficiency (PE), current efficiency (CE), and external quantum efficiency (EQE) of 82.3 lm/W, 70.0 cd/A, and 22.2%, respectively. Our results presented here provided a new option for promoting simple-structure hybrid WOLEDs with superior performance.

Perfluorinated compounds in poultry products from the Yangtze River Delta and Pearl River Delta regions in China.

Chicken, duck, egg, and duck egg samples from the Yangtze River Delta and Pearl River Delta regions in China were analyzed for 17 perfluorinated compounds (PFCs). The concentrations of PFCs in chicken and duck livers ranged from

Design and Synthesis of Donor-σ-π-σ-Acceptor-Type Dispiro Molecules.

Two novel donor-σ-π-σ-acceptor-type dispiro molecules-10-phenyl-10H-dispiro-acridine-9,9'-anthracene-10',9''-fluorene-2'',7''-dicarbo-nitrile (DiSAAF) and dispiro-fluorene-9,9'-anthracene-10',9''-quinolino[3,2,1-kl]phenoxazine-2,7-dicarbonitrile (DiSFAQ)-with excellent thermal stability are designed and synthesized. Both materials exhibit blocked long-range intramolecular charge transfer but show intermolecular charge-transfer emission in the film state. Their photophysical and thermal properties then are fully investigated and a maximum external quantum efficiency of 21.7% of the red phosphorescent device is achieved by DiSAAF.