Andrographolide suppresses the malignancy of pancreatic cancer via alleviating DNMT3B-dependent repression of tumor suppressor gene ZNF382.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type that urgently requires effective therapeutic strategies. Andrographolide, a labdane diterpenoid compound abundant in Andrographis paniculata, has anticancer effects against various cancer types, but its anticancer activity and mechanism against PDAC remain largely uncharacterized. PURPOSE: This study explores novel drug target(s) and underlying molecular mechanism of andrographolide against PDAC. STUDY DESIGN AND METHODS: The malignant phenotypes of PDAC cells, PANC-1 and MIA PaCa-2 cells, were measured using MTT, clonogenic assays, and Transwell migration assays. A PDAC xenograft animal model was used to evaluate tumor growth in vivo. Western blot, immunofluorescence and immunohistochemistry were used for measuring protein expression. The TCGA database was analyzed to evaluate promoter methylation status, gene expression, and their relationship with patient survival rates. RT-qPCR was used for detecting mRNA expression. Reporter assays were used for detecting signal transduction pathways. Promoter DNA methylation was determined by sodium bisulfite treatment and methylation-specific PCR (MSP). The biological function and role of specific genes involved in drug effects were measured through gene overexpression. RESULTS: Andrographolide treatment suppressed the proliferation and migration of PDAC cells and impaired tumor growth in vivo. Furthermore, andrographolide induced the mRNA and protein expression of zinc finger protein 382 (ZNF382) in PDAC cells. Overexpression of ZNF382 inhibited malignant phenotypes and cancer-associated signaling pathways (AP-1, NF-κB and ß-catenin) and oncogenes (ZEB-1, STAT-3, STAT-5, and HIF-1α). Overexpression of ZNF382 delayed growth of PANC-1 cells in vivo. ZNF382 mRNA and protein expression was lower in tumor tissues than in adjacent normal tissues of pancreatic cancer patients. Analysis of the TCGA database found the ZNF382 promoter is hypermethylated in primary pancreatic tumors which correlates with its low expression. Furthermore, andrographolide inhibited the expression of DNA methyltransferase 3 beta (DNMT3B) and increased the demethylation of the ZNF382 promoter in PDAC cells. Overexpression of DNMT3B attenuated the andrographolide-suppressed proliferation and migration of PDAC cells. CONCLUSION: Our finding revealed that ZNF382 acts as a tumor suppressor gene in pancreatic cancer and andrographolide restores ZNF382 expression to suppress pancreatic cancer, providing a novel molecular target and a promising therapeutic approach for treating pancreatic cancer.

Prognostic Prediction Value and Biological Functions of Non-Apoptotic Regulated Cell Death Genes in Lung Adenocarcinoma.

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.

CD73, a significant protein in liver diseases.

Purine adenosine pathway exists widely in the body metabolism, and is involved in regulating various physiological processes. It is one of the important pathways of environmental regulation in human body. CD73 is essentially a protease that catalyzes further dephosphorylation of extracellular adenine nucleotides, hydrolyzing extracellular AMP to adenosine and phosphate. CD73 is an important part of the adenosine signaling pathway. Studies have shown that CD73-mediated adenosine pathway can convert the inflammatory ATP into the immunosuppressant adenosine. This paper aims to summarize the relevant effects of CD73 in the occurrence, development and prognosis of liver diseases such as viral hepatitis, highlight the important role of CD73 in liver diseases, especially in viral hepatitis such as HBV and HCV, and explore new clinical ideas for future treatment targets of liver diseases.

Tunable luminescence and efficient energy transfer investigation of a borosilicate phosphor KBSi2O6: Bi3+, Eu3+ with hypersensitive thermal quenching.

Energy transfer between Bi3+ and Eu3+ has undergone substantial research but Bi3+ and Eu3+ co-doped luminescent materials with high energy transfer efficiency for temperature sensing are rarely investigated until now. Herein, Eu3+ and Bi3+ co-doped KBSi2O6 phosphors were successfully synthesized by solid-state reaction method. The phase purity structure as well as the element distribution were carefully investigated through X-ray diffraction structural refinement and energy dispersive spectrometer analysis. The characteristic luminescence property and luminescence kinetics of KBSi2O6: Bi3+, Eu3+ were investigated. By the large spectra overlap between the emission spectrum of Bi3+ and excitation spectrum of Eu3+, the energy transfer from Bi3+ to Eu3+ can be inferred. The corresponding decrease of the emission intensity and decay time of Bi3+ in KBSi2O6: Bi3+, Eu3+ provided direct evidence for the effective energy transfer from Bi3+ to Eu3+. The interaction and energy transfer mechanism between Bi3+ and Eu3+ ions were also studied. By increasing the Eu3+ concentration in KBSi2O6: Bi3+, Eu3+, the color-tunable emission from blue to red can be realized. KBSi2O6: Bi3+, Eu3+ shows hypersensitive thermal quenching behavior and the maximum absolute sensitivity (Sa) and relative sensitivity (Sr) are determined to be 1.87 %K-1 and 2.895 %K-1, respectively. All of the above results imply that KBSi2O6: Bi3+, Eu3+ phosphor can be a color-tunable phosphor for optical temperature sensing.

Microbial community structural response to variations in physicochemical features of different aquifers.

Introduction: The community structure of groundwater microorganisms has a significant impact on groundwater quality. However, the relationships between the microbial communities and environmental variables in groundwater of different recharge and disturbance types are not fully understood. Methods: In this study, measurements of groundwater physicochemical parameters and 16S rDNA high-throughput sequencing technology were used to assess the interactions between hydrogeochemical conditions and microbial diversity in Longkou coastal aquifer (LK), Cele arid zone aquifer (CL), and Wuhan riverside hyporheic zone aquifer (WH). Redundancy analysis indicated that the primary chemical parameters affecting the microbial community composition were NO3 -, Cl-, and HCO3 -. Results: The species and quantity of microorganisms in the river-groundwater interaction area were considerably higher than those in areas with high salinity [Shannon: WH (6.28) > LK (4.11) > CL (3.96); Chao1: WH (4,868) > CL (1510) > LK (1,222)]. Molecular ecological network analysis demonstrated that the change in microbial interactions caused by evaporation was less than that caused by seawater invasion under high-salinity conditions [(nodes, links): LK (71,192) > CL (51,198)], whereas the scale and nodes of the microbial network were greatly expanded under low-salinity conditions [(nodes, links): WH (279,694)]. Microbial community analysis revealed that distinct differences existed in the classification levels of the different dominant microorganism species in the three aquifers. Discussion: Environmental physical and chemical conditions selected the dominant species according to microbial functions. Gallionellaceae, which is associated with iron oxidation, dominated in the arid zones, while Rhodocyclaceae, which is related to denitrification, led in the coastal zones, and Desulfurivibrio, which is related to sulfur conversion, prevailed in the hyporheic zones. Therefore, dominant local bacterial communities can be used as indicators of local environmental conditions.

Yang-Gan-Jiang-Mei formula alleviates non-alcoholic steatohepatitis by inhibiting NLRP3 inflammasome through mitophagy.

As an effective formula of traditional Chinese medicine, Yang-Gan-Jiang-Mei (YGJM) formula exhibited a unique advantage in ameliorating liver injury and hepatic steatosis of non-alcoholic steatohepatitis (NASH). Nevertheless, the related pharmacological mechanism needs to be elucidated. This study aimed to explore the molecular mechanism of YGJM formula on mitophagy mediated by PINK1/parkin signaling pathway and NOD-like receptor protein 3 (NLRP3) inflammasome in NASH. High-fat-diet rats and HepG2 cells induced by free fatty acid were used as NASH models in vivo and in vitro. Liver pathology and serum indicator embodying liver function (aspartate transferase, alanine transferase, triglyceride, and total cholesterol) were applied to evaluate the extent of hepatic damage and lipid accumulation. Besides, transmission electron microscopy, JC-1 and 2',7'-dichlorofluorescein diacetate were utilized to observe hepatic mitochondrial morphology, as well as cellular mitochondrial membrane potential and reactive oxygen species level. Additionally, expression of PINK1/parkin-mediated mitophagy and NLRP3 inflammasome was detected to elucidate the underlying mechanism of YGJM formula by immunohistochemistry, immunofluorescence, RT-PCR (reverse transcription-polymerase chain reaction) and Western blot. The manifestations of pathology and biochemical detection confirmed the efficacy of YGJM formula in relieving hepatic damage and lipid deposition. Simultaneously, YGJM formula could obviously improve mitochondrial function. In addition, YGJM formula exhibited the promotion of PINK1/parkin-mediated mitophagy, which could perturb NLRP3 inflammasome activation, and as a result, the hepatocyte inflammation was also suppressed both in vitro and in vivo. Our preliminary results indicate that YGJM formula can ameliorate NASH mechanistically by interfering with PINK1/parkin-mediated mitophagy and NLRP3 inflammasome to exert anti-inflammation ability and promote mitochondrial function restoration.

Progress in research on the role played by myeloid-derived suppressor cells in liver diseases.

Myeloid-derived suppressor cells (MDSCs) refer to a group of immature myeloid cells with potent immunosuppressive capacity upon activation by pathological conditions. Because of their potent immunosuppressive ability, MDSCs have garnered extensive attention in the past few years in the fields of oncology, infection, chronic inflammation and autoimmune diseases. Research on MDSCs in liver diseases has gradually increased, and their potential therapeutic roles will be further explored. This review presents a summary of the involvement and the role played by MDSCs in liver diseases, thus identifying their potential targets for the treatment of liver diseases and providing new directions for liver disease-related research.

Simulation of regional groundwater levels in arid regions using interpretable machine learning models.

Regional groundwater level forecasting is critical to water resource management, especially for arid regions which require effective management of groundwater resources to meet human and ecosystem needs. In this study Machine Learning and Deep Learning approaches - Support Vector Machine, Generalized Regression Neural Network, Decision Tree, Random Forest (RF), Convolutional Neural Network, Long Short Term Memory and Gated Recurrent Network- have been used to simulate the groundwater levels in the lower Tarim River basin (LTRB) which is an extreme dryland. The results showed that models developed here with easily available input data such as relative humidity, flow volume and distance to the riverbank can fully utilize spatiotemporally inconsistent groundwater monitoring data to predict the spatiotemporal variation of the groundwater system in arid regions where exist intermittent flow. The shapely additive explanations method was used to interpret the RF model and discover the effect of meteorological, hydrological and environmental variables on the regional groundwater. These explanations showed that the flow volume, the distance to the river channel and reservoir have a critical impact on groundwater changes. Within 300 m distance to the riverbank, groundwater would mainly be influenced by the flow volume and the distance to the reservoir. While far from the riverbank, these effects decreased gradually further away from the river course. The RF prediction results showed that in the next three years (2021-2023), the groundwater level on average may decline to -6.4 m, and the suitable areas for natural vegetation growth would be limited to 39% if no water conveyance in the LTRB. To guarantee the stability of ecosystems in the LTRB, it is necessary to convey the water annually. These results can support spatiotemporal predictions of groundwater levels predominantly recharged by intermittent flow, and form a scientific basis for sustainable water resources management in arid regions.

Manipulation of amorphous precursors to enhance zeolite nucleation.

Crystallization in media comprised of amorphous precursors is becoming a more common phenomenon for numerous synthetic, biological, and natural materials that grow by a combination of classical and nonclassical pathways. Amorphous phases can exhibit a wide range of physicochemical properties that may evolve during the course of nucleation and crystal growth. This creates challenges for establishing causal relationships between amorphous precursor properties and their effect(s) on the selection of mechanistic pathways of crystallization and ultimately the properties of the crystalline product. In this study, we examine ways to manipulate the composition and colloidal stability of amorphous (alumino)silicate precursors that are prevalent in nanoporous zeolite syntheses. Changes in the amorphous precursor properties are evaluated on the basis of their ability to enhance rates of crystal formation. Here, we use fumed silica as the primary silicon source and examine the effects of infusing the source or growth medium with additional alkali metal, which serves as an inorganic structure-directing agent to facilitate the formation of porous crystal structures. We also assess the impact of adding a polymer additive, which reduces the colloidal stability of precursors, wherein we posit that the confined pockets of solution within the interstitial spaces of the precursor aggregates play an important role in regulating the rate of zeolite crystallization. Three commercially relevant zeolites (mordenite, SSZ-13, and ZSM-5) were selected for this study based on their diverse frameworks and methods of preparation. Our findings reveal that alkali infusion significantly reduces the crystallization times for mordenite and SSZ-13, but has little impact on ZSM-5 synthesis. Conversely, we find that polymer addition markedly enhanced the rates of crystallization among all three zeolites, suggesting that this method may be a general approach to reduce zeolite synthesis times. Given the relatively high costs associated with commercial zeolite production, identifying new methods to improve the efficiency of hydrothermal syntheses can have significant practical implications beyond the fundamental benefits of developing new routes to tailor nonclassical crystallization.

Oasis sustainability assessment in arid areas using GRACE satellite data.

An oasis is an important habitat for humans, plants, and wildlife in arid desert areas. The sustainability of an oasis is crucial for a smooth regional ecological functioning and healthy economic development. However, the overexploitation of groundwater will result in unsustainable oasis development. Due to the lack of long-term groundwater monitoring data, the impact of groundwater level changes on the sustainability of an oasis has not been studied extensively. In the present study, we used the ground water storage anomaly (GWSA) in combination with the Gravity Recovery and Climate Experiment (GRACE) and the Global Land Data Assimilation System (GLDAS) for the rapid identification of oasis sustainability, which has been tested and evaluated in Hotan and Qira oasis located in arid areas. The results showed that (1) the GWSA is a suitable and reliable indicator for trend change analysis in small-scale oasis and, (2) additionally, M-K test results for long-term trend change of GWSA showed a positive correlation with water resource carrying capacity (WRCC). These results suggest that GWSA can be used as a reliable index for the rapid assessment of oasis sustainability status in arid areas. Moreover, the potential applicability of GRACE satellite data in evaluating the groundwater sustainability in arid areas lacking proper data has also been proved in this study. These findings have provided a foundation to evaluate the sustainability status of an oasis and set a reference point to formulate future policies for the oasis.

Accelerating the Crystallization of Zeolite SSZ-13 with Polyamines.

Tailoring processes of nucleation and growth to achieve desired material properties is a pervasive challenge in synthetic crystallization. In systems where crystals form via nonclassical pathways, engineering materials often requires the controlled assembly and structural evolution of colloidal precursors. In this study, we examine zeolite SSZ-13 crystallization and show that several polyquaternary amines function as efficient accelerants of nucleation, and, in selected cases, tune crystal size by orders of magnitude. Among the additives tested, polydiallyldimethylammonium (PDDA) was found to have the most pronounced impact on the kinetics of SSZ-13 formation, leading to a 4-fold reduction in crystallization time. Our findings also reveal that enhanced nucleation occurs at an optimal PDDA concentration where a combination of light-scattering techniques demonstrate these conditions lead to polymer-induced aggregation of amorphous precursors and the promotion of (alumino)silicate precipitation from the growth solution. Here, we show that relatively low concentrations of polymer additives can be used in unique ways to dramatically enhance SSZ-13 crystallization rates, thereby improving the overall efficiency of zeolite synthesis.

Mechanism by which Huoxue Tongluo Qiwei Decoction improves the erectile function of rats with diabetic erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. RATIONALE: To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. MATERIALS AND METHODS: The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. CONCLUSION: Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCß signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

Spatial distribution and source apportionment of polycyclic aromatic hydrocarbons in typical oasis soil of north-western China and the bacterial community response.

Oases environments in oases to be sensitive to anthropogenic activity because of ecological fragility. Polycyclic aromatic hydrocarbon (PAH) pollution resulting from anthropogenic activity leads to ecological degradation in oases. To examine the impact of anthropogenic activity on the oasis ecological environment, the present study focused on the spatial distribution and source apportionment of soil PAHs and bacterial community responses in typical oases in Xinjiang, China. The results showed that the soil PAH level were higher in the city centres of Urumqi (9-6340 µg kg-1), Aksu (8-957 µg kg-1) and Korla (8-1103 µg kg-1) and lower in the centres of Hotan city (11-268 µg kg-1) and Qira county (7-163 µg kg-1). Source apportionment suggested that gasoline emissions, diesel emissions, vehicle emissions, coal combustion, coke processing and biomass burning were the sources of soil PAHs. The integrated lifetime cancer risks of soil PAH exceeding the guideline safety values (10-6) recommended by United States Environmental Protection Agency. The ingestion and dermal exposure pathways caused the greatest health risk (contribution ≤82%). Additionally, in the soil with low PAH concentrations, the richness and evenness of the soil bacterial community were great, and the molecular ecological network (MEN) structure was complex. Among populations, Proteobacteria and Actinobacteria (relative abundance ≥17%) are the main dominant species in the bacterial communities and the keystone species in the MEN.

Enhanced Selectivity and Stability of Finned Ferrierite Catalysts in Butene Isomerization.

Designing zeolite catalysts with improved mass transport properties is crucial for restrictive networks of either one- or two-dimensional pore topologies. Here, we demonstrate the synthesis of finned ferrierite (FER), a commercial zeolite with two-dimensional pores, where protrusions on crystal surfaces behave as pseudo nanoparticles. Catalytic tests of 1-butene isomerization reveal a 3-fold enhancement of catalyst lifetime and an increase of 12 % selectivity to isobutene for finned samples compared to corresponding seeds. Electron tomography was used to confirm the identical crystallographic registry of fins and seeds. Time-resolved titration of Brønsted acid sites confirmed the improved mass transport properties of finned ferrierite compared to conventional analogues. These findings highlight the advantages of introducing fins through facile and tunable post-synthesis modification to impart material properties that are otherwise unattainable by conventional synthesis methods.

Explore the effects of pulmonary fibrosis on sperm quality and the role of the PI3K/Akt pathway based on rat model.

Researches were reported that respiratory diseases can lead to male infertility; however, it is unclear whether there is a relationship between pulmonary fibrosis (PF) and male infertility. This study examined the influence of PF on sperm quality and its mechanisms. The key signalling pathway of male infertility caused by PF was predicted based on bioinformatics research. After modelling, we evaluated semen quality. Real-time quantitative polymerase chain reaction and Western blotting were used to measure the protein and mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylation-protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl2) in rat testicular cells. Compared with group A (48.77 ± 4.67; 59.77 ± 4.79), the sperm concentration and total sperm viability of group B (8.44 ± 1.71; 15.39 ± 3.48) showed a downward trend (p < 0.05). Western blotting showed that the protein expressions of PI3K, p-Akt and Bcl2 in the testes of group B (0.30 ± 0.06; 0.27 ± 0.05; 0.15 ± 0.03) was significantly lower than those of group A (0.71 ± 0.07; 0.72 ± 0.06; 0.50 ± 0.06) (p < 0.05). The hypoxic environment induced by PF can inhibit the expression of PI3K, p-Akt and Bcl2 protein and eventually cause dysfunctional spermatogenesis.

An Empirical Study of Training Data Selection Methods for Ranking-Oriented Cross-Project Defect Prediction.

Ranking-oriented cross-project defect prediction (ROCPDP), which ranks software modules of a new target industrial project based on the predicted defect number or density, has been suggested in the literature. A major concern of ROCPDP is the distribution difference between the source project (aka. within-project) data and target project (aka. cross-project) data, which evidently degrades prediction performance. To investigate the impacts of training data selection methods on the performances of ROCPDP models, we examined the practical effects of nine training data selection methods, including a global filter, which does not filter out any cross-project data. Additionally, the prediction performances of ROCPDP models trained on the filtered cross-project data using the training data selection methods were compared with those of ranking-oriented within-project defect prediction (ROWPDP) models trained on sufficient and limited within-project data. Eleven available defect datasets from the industrial projects were considered and evaluated using two ranking performance measures, i.e., FPA and Norm(Popt). The results showed no statistically significant differences among these nine training data selection methods in terms of FPA and Norm(Popt). The performances of ROCPDP models trained on filtered cross-project data were not comparable with those of ROWPDP models trained on sufficient historical within-project data. However, ROCPDP models trained on filtered cross-project data achieved better performance values than ROWPDP models trained on limited historical within-project data. Therefore, we recommended that software quality teams exploit other project datasets to perform ROCPDP when there is no or limited within-project data.

Improving Ponzi Scheme Contract Detection Using Multi-Channel TextCNN and Transformer.

With the development of blockchain technologies, many Ponzi schemes disguise themselves under the veil of smart contracts. The Ponzi scheme contracts cause serious financial losses, which has a bad effect on the blockchain. Existing Ponzi scheme contract detection studies have mainly focused on extracting hand-crafted features and training a machine learning classifier to detect Ponzi scheme contracts. However, the hand-crafted features cannot capture the structural and semantic feature of the source code. Therefore, in this study, we propose a Ponzi scheme contract detection method called MTCformer (Multi-channel Text Convolutional Neural Networks and Transofrmer). In order to reserve the structural information of the source code, the MTCformer first converts the Abstract Syntax Tree (AST) of the smart contract code to the specially formatted code token sequence via the Structure-Based Traversal (SBT) method. Then, the MTCformer uses multi-channel TextCNN (Text Convolutional Neural Networks) to learn local structural and semantic features from the code token sequence. Next, the MTCformer employs the Transformer to capture the long-range dependencies of code tokens. Finally, a fully connected neural network with a cost-sensitive loss function in the MTCformer is used for classification. The experimental results show that the MTCformer is superior to the state-of-the-art methods and its variants in Ponzi scheme contract detection.

Few-Unit-Cell MFI Zeolite Synthesized using a Simple Di-quaternary Ammonium Structure-Directing Agent.

Synthesis of a pentasil-type zeolite with ultra-small few-unit-cell crystalline domains, which we call FDP (few-unit-cell crystalline domain pentasil), is reported. FDP is made using bis-1,5(tributyl ammonium) pentamethylene cations as structure directing agent (SDA). This di-quaternary ammonium SDA combines butyl ammonium, in place of the one commonly used for MFI synthesis, propyl ammonium, and a five-carbon nitrogen-connecting chain, in place of the six-carbon connecting chain SDAs that are known to fit well within the MFI pores. X-ray diffraction analysis and electron microscopy imaging of FDP indicate ca. 10 nm crystalline domains organized in hierarchical micro-/meso-porous aggregates exhibiting mesoscopic order with an aggregate particle size up to ca. 5 µm. Al and Sn can be incorporated into the FDP zeolite framework to produce active and selective methanol-to-hydrocarbon and glucose isomerization catalysts, respectively.

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology.

CONTEXT: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE: Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 µg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

A Bioinformatic Investigation of the Mechanism Underlying Migraine-Induced Erectile Dysfunction.

BACKGROUND: Over recent years, an increasing body of literature has focused on the relationship between erectile dysfunction (ED) and migraine. However, the specific mechanism is unclear. MATERIALS AND METHODS: We used a bioinformatic database to predict the targets and pathways associated with migraine and ED. Twenty male SD rats were randomly divided into a blank group (Group A, n = 10) and a migraine model group (Group B, n = 10). The rats in Group A were subcutaneously injected with normal saline (2 ml/kg) into the back of the neck. Rats in Group B were subcutaneously injected with nitroglycerin 10 mg/kg (5 mg/ml) into the back of the neck in order to create an animal model of migraine. Next, we carried out the measurement of erectile function. We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Western blotting was used to determine the expression levels of PI3K, p-AKT, and p-mTOR in the protein; Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was used to determine the expression levels of PI3K, AKT, and mTOR in the messenger ribonucleic acid (mRNA). RESULTS: There are 117 intersection targets of migraine and ED, involving 188 cell biological processes (BP), 21 cellular components (CC), 31 molecular functions (MF), and 65 signaling pathways. HE staining results show that there were no significant differences between Group A and Group B with regard to any of the parameters. Compared with Group A, the levels of the PI3K, p-AKT, and p-mTOR proteins and PI3K, AKT, and mTOR mRNAs in Group B decreased (P < 0.01). CONCLUSIONS: The decline of erectile function in a rat model of migraine was associated with the PI3K/Akt/mTOR signaling pathway.