Research on a Framework for Chinese Argot Recognition and Interpretation by Integrating Improved MECT Models.

In underground industries, practitioners frequently employ argots to communicate discreetly and evade surveillance by investigative agencies. Proposing an innovative approach using word vectors and large language models, we aim to decipher and understand the myriad of argots in these industries, providing crucial technical support for law enforcement to detect and combat illicit activities. Specifically, positional differences in semantic space distinguish argots, and pre-trained language models' corpora are crucial for interpreting them. Expanding on these concepts, the article assesses the semantic coherence of word vectors in the semantic space based on the concept of information entropy. Simultaneously, we devised a labeled argot dataset, MNGG, and developed an argot recognition framework named CSRMECT, along with an argot interpretation framework called LLMResolve. These frameworks leverage the MECT model, the large language model, prompt engineering, and the DBSCAN clustering algorithm. Experimental results demonstrate that the CSRMECT framework outperforms the current optimal model by 10% in terms of the F1 value for argot recognition on the MNGG dataset, while the LLMResolve framework achieves a 4% higher accuracy in interpretation compared to the current optimal model.The related experiments undertaken also indicate a potential correlation between vector information entropy and model performance.

Fluorescence and Lifetime Imaging of Endoplasmic Reticulum Polarity Change During Ferroptosis.

As a new form of regulated cell death, ferroptosis is closely related to various diseases. Tracing ferroptosis related biological behavior is helpful to better understand this process and its related biology. Considering that ferroptosis is featured with remarkable lipid peroxidation which can easily change the membranes' compositions and structures, it is potential to detect intracellular environmental changes for direct assessment of ferroptosis. In view of the close relationship between endoplasmic reticulum (ER) and ferroptosis, we designed an ER-targeted and polarity-sensitive fluorescent probe SBD-CH, which has superior photostability and can respond to polarity with high selectivity without the affection of viscosity. SBD-CH can monitor the trend of ER polarity during ferroptosis by confocal laser scanning microscopy (CLSM), and analyze the distribution of polarity in ferroptosis by fluorescence lifetime imaging microscopy (FLIM). During Erastin induced ferroptosis, the polarity of ER in HT-1080 cells increased and the polarity distribution in ER was more dispersed. Our work provides an effective strategy for evaluating the process of ferroptosis by monitoring the changes of ER polarity.

In-Depth Review of Loeffler Endocarditis: What Have We Learned?

Loeffler endocarditis, eosinophilic endocarditis or eosinophilic endomyocardial disease are conditions associated with hypereosinophilia and they affect the heart function. Loeffler endocarditis is a rare endomyocardial disorder thought to be caused by eosinophilic damage. The disorder is characterized by inflammatory infiltration, formation of thrombus within cardiovascular system, and ultimately fibrosis of the afflicted area. It can lead to multiple severe complications, including thromboembolic disease, thickening of fibrous tissue in the endocardium of ventricles, valve involvement, apical obliteration, and various heart disorders. Although early clinical intervention can lead to remission, the underlying mechanisms of the disorder remain unresolved. In the present article, we summarise the existing literature concerning Loeffler endocarditis based on PubMed, Web of Science, and other medical databases to conduct an in-depth review of the epidemiology, etiology, pathophysiological mechanisms, staging, diagnosis, treatment and prognosis of Loeffler endocarditis. Meanwhile, we provide novel patients data and clinical figures of Loeffler endocarditis to supplement the understanding of this cardiac disorder. The findings presented in this article provide a basis for further studies and can be used to improve management of the disorder.

X-Ray Calc 3: improved software for simulation and inverse problem solving for X-ray reflectivity.

This work introduces X-Ray Calc (XRC), an open-source software package designed to simulate X-ray reflectivity (XRR) and address the inverse problem of reconstructing film structures on the basis of measured XRR curves. XRC features a user-friendly graphical interface that facilitates interactive simulation and reconstruction. The software employs a recursive approach based on the Fresnel equations to calculate XRR and incorporates specialized tools for modeling periodic multilayer structures. This article presents the latest version of the X-Ray Calc software (XRC3), with notable improvements. These enhancements encompass an automatic fitting capability for XRR curves utilizing a modified flight particle swarm optimization algorithm. A novel cost function was also developed specifically for fitting XRR curves of periodic structures. Furthermore, the overall user experience has been enhanced by developing a new single-window interface.

A novel MICA/B-targeted chimeric antigen receptor augments the cytotoxicity of NK cells against tumor cells.

Chimeric antigen receptor (CAR)-modified immune cells have emerged as a promising approach for cancer treatment, but single-target CAR therapy in solid tumors is limited by immune escape caused by tumor antigen heterogeneity and shedding. Natural killer group 2D (NKG2D) is an activating receptor expressed in human NK cells, and its ligands, such as MICA and MICB (MICA/B), are widely expressed in malignant cells and typically absent from healthy tissue. NKG2D plays an important role in anti-tumor immunity, recognizing tumor cells and initiating an anti-tumor response. Therefore, NKG2D-based CAR is a promising CAR candidate. Nevertheless, the shedding of MICA/B hinders the therapeutic efficacy of NKG2D-CARs. Here, we designed a novel CAR by engineering an anti-MICA/B shedding antibody 1D5 into the CAR construct. The engineered NK cells exhibited significantly enhanced cytotoxicity against various MICA/B-expressing tumor cells and were not inhibited by NKG2D antibody or NKG2D-Fc fusion protein, indicating no interference with NKG2D-MICA/B binding. Therefore, the developed 1D5-CAR could be combined with NKG2D-CAR to further improve the obstacles caused by MICA/B shedding.

VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model.

Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating neurological disorders. Herein, we investigated the effects of VEGF-C overexpression on brain fluid drainage and ischemic stroke outcomes in mice. Intracerebrospinal administration of an adeno-associated virus expressing mouse full-length VEGF-C (AAV-mVEGF-C) increased CSF drainage to the deep cervical lymph nodes (dCLNs) by enhancing lymphatic growth and upregulated neuroprotective signaling pathways identified by single nuclei RNA sequencing of brain cells. In a mouse model of ischemic stroke, AAV-mVEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage, associated with mitigated microglia-mediated inflammation and increased BDNF signaling in brain cells. Neuroprotective effects of VEGF-C were lost upon cauterization of the dCLN afferent lymphatics and not mimicked by acute post-stroke VEGF-C injection. We conclude that VEGF-C prophylaxis promotes multiple vascular, immune, and neural responses that culminate in a protection against neurological damage in acute ischemic stroke.

Developing an Approach for Calculating Theoretical Minimum Hydrogen Consumption during Catalytic Hydrotreating of Diesel.

Identifying the unnecessary H2 consumption existing in diesel hydrotreating process and calculating theoretical minimum H2 consumption are extremely critical for reducing H2 consumption in consideration of carbon reduction and resource utilization improvement. In this work, chemical reactions happened during diesel hydrotreating were categorized into hydrodesulfurization (HDS), hydrodenitrogenation (HDN), saturation of monocyclic aromatic hydrocarbons (MAHs), saturation of polycyclic aromatic hydrocarbons (PAHs), hydrogenation of olefins (HGO) and hydrocracking reactions (HCR). Then, in order to gain insights into where and how much H2 can be reduced, the ideal molecular compositions of the products were analyzed when theoretical minimum H2 was achieved for each type of reactions, which can give a genuine value of average relative molecular weight and average number of moles of H2 consumed per mole of reactants, leading to the establishment of method for calculating theoretical minimum H2 consumption. Additionally, the above method was used to calculate theoretical minimum H2 consumption of five diesel feedstocks with different properties to study the influence of content of S, N and PAHs in the feed on theoretical minimum H2 consumption. This method can provide guidance for experiments of H2 consumption reduction, and also help the refineries to save potential costs of H2.

Enhancing CO catalytic oxidation performance over Cu-doping manganese oxide octahedral molecular sieves catalyst.

The CO oxidation catalytic activity of catalysts is strongly influenced by the oxygen vacancy defects (OVDs) concentration and the valence state of active metal. Herein, a defect engineering approach was implemented to enhance the oxygen vacancy defects and to modify the valence of metal ions in manganese oxide octahedral molecular sieves (OMS-2) by the introduction of copper (Cu). The characterization and theoretical calculation results reveal that the incorporation of Cu2+ ion into the OMS-2 structure led to a rise in specific surface area and pore volume, weakening of Mn-O bonds, higher proportion of the low-coordinated oxygen species adsorbed in oxygen vacancies (Oads) and an increase in the average oxidation state of manganese. These structural modifications were discovered to considerably reduce the apparent activation energy (Ea), thus ultimately significantly enhancing the CO oxidation activity (T99 at 148 ℃at GHSV = 13,200 h-1) than the original OMS-2 (T99 = 215 ℃ at GHSV = 13,200 h-1). Furthermore, In-situ diffuse reflectance infrared Fourier transform (DRIFT) and In-situ near-ambient pressure X-ray photoelectron spectroscopy (in situ NAP-XPS) results indicate that the bimetallic synergy enhanced by doping strategy accelerates the conversion of oxygen to chemisorbed oxygen species and the reaction rate of CO oxidation through Mn3++Cu2+↔Mn4++Cu+ redox cycle. The findings of this study offer novel perspectives on the design of catalysts with exceptional performance in CO oxidation.

Combining physical & cognitive training with iPSC-derived dopaminergic neuron transplantation promotes graft integration & better functional outcome in parkinsonian marmosets.

Parkinson's disease (PD) is a relentlessly progressive and currently incurable neurodegenerative disease with significant unmet medical needs. Since PD stems from the degeneration of midbrain dopaminergic (DA) neurons in a defined brain location, PD patients are considered optimal candidates for cell replacement therapy. Clinical trials for cell transplantation in PD are beginning to re-emerge worldwide with a new focus on induced pluripotent stem cells (iPSCs) as a source of DA neurons since they can be derived from adult somatic cells and produced in large quantities under current good manufacturing practices. However, for this therapeutic strategy to be realized as a viable clinical option, fundamental translational challenges need to be addressed including the manufacturing process, purity and efficacy of the cells, the method of delivery, the extent of host reinnervation and the impact of patient-centered adjunctive interventions. In this study we report on the impact of physical and cognitive training (PCT) on functional recovery in the nonhuman primate (NHP) model of PD after cell transplantation. We observed that at 6 months post-transplant, the PCT group returned to normal baseline in their daily activity measured by actigraphy, significantly improved in their sensorimotor and cognitive tasks, and showed enhanced synapse formation between grafted cells and host cells. We also describe a robust, simple, efficient, scalable, and cost-effective manufacturing process of engraftable DA neurons derived from iPSCs. This study suggests that integrating PCT with cell transplantation therapy could promote optimal graft functional integration and better outcome for patients with PD.

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy.

BACKGROUND: Hepatocellular carcinoma (HCC) with major portal vein invasion (MPVI) presents very poor outcomes. Hepatic artery infusion chemotherapy (HAIC) and radiation therapy (RT) have both been found to be effective for advanced HCC. In this retrospective study, we compared the therapeutic outcomes of our "new" HAIC regimen with and without concurrent RT, before and after propensity score matching (PSM) in treating HCC patients with MPVI. METHODS: One hundred forty patients with MPVI received HAIC alone and 35 patients underwent concurrent HAIC and RT during a 16-year period. The left subclavian artery was adopted as the entry site for a temporary catheter placement for a 5-day chemoinfusion. The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was adopted to assess the objective response rate (ORR). The Kaplan-Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS) between the two groups. Univariate and multivariate analyses by Cox regression model were used to assess hazard ratios. RESULTS: Of the 140 patients with Child-Pugh A liver function, the median OS was 17.0 months. In the initial cohort, higher ORR and PFS were found in the concurrent RT group than in the HAIC alone group (80% vs 66.4% and 9 vs 8 months, respectively) but shorter OS (10.5 vs 14.5 months, p = 0.039) was observed. After PSM, the OS was 10 and 15 months ( p = 0.012), respectively. Multivariable Cox regression analysis revealed that the significant factors for adjusting hazard ratios for OS were Child-Pugh classification, alpha fetal protein (AFP) level, and hepatic vein invasion. CONCLUSION: HAIC is an effective treatment for advanced HCC patients with MPVI. Concurrent HAIC and full-dose RT were associated with worse clinical outcomes.

circRARS synergises with IGF2BP3 to regulate RNA methylation recognition to promote tumour progression in renal cell carcinoma.

As the most prominent RNA modification, N6-methyladenosine (m6 A) participates in the regulation of tumour initiation and progression. Circular RNAs (circRNAs) also play crucial roles in ubiquitous life processes. Whether circRNAs are required for m6 A regulation in renal cell carcinoma (RCC) remains unclear. Meta-analysis and bioinformatics identified that IGF2BP3 was upregulated in RCC and indicated a worse prognosis. IGF2BP3 significantly promoted RCC progression in vitro and in vivo. Mechanistically, circRARS bound to KH1-KH2 domains of IGF2BP3 to enhance m6 A modification recognition. A 12-nt sequence (GUCUUCCAGCAA) was proven to be the IGF2BP3-binding site of circRARS. Additionally, CAPN15, CD44, HMGA2, TNRC6A and ZMIZ2 were screened to be the target genes regulated by the IGF2BP3/circRARS complex in an m6 A-dependent manner. Stabiliser proteins, including HuR, Matrin3 and pAbPC1, were recruited by circRARS, thereby increasing the mRNA stability of the forementioned five target genes. Consequently, the IGF2BP3/circRARS complex facilitated the lipid accumulation of RCC cells and promoted sunitinib resistance via target genes. circRARS synergised with IGF2BP3 to facilitate m6 A recognition, thereby promoting RCC progression. Thus, IGF2BP3 could be a potential biomarker for RCC diagnosis and prognosis and a therapeutic target.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and the Risk of Developing Incidental Tuberculosis: A Population-Based Cohort Study.

Background and Objectives: Treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) must deal with immunosuppression, as well as infections associated with a compromised immune system, such as tuberculosis (TB). Our aim was to examine the risk of incidental TB after diagnosis of AAV. Materials and Methods: This retrospective population-based cohort study was based on the data from the National Health Insurance Research Database in Taiwan. Patients with newly diagnosed granulomatous polyangiitis or microscopic polyangiitis were identified between 1 January 2000 and 31 December 2012. The primary outcome was risk of incidental TB. Cox proportional hazard models were used to evaluate the association between AAV and incidental TB. Results: A total of 2257 patients with AAV and a propensity-score matched cohort of 9028 patients were studied. Overall, patients with AAV were at a 1.48× higher risk of contracting incidental TB than the patients in the matched cohort (adjusted HR 1.48; 95% confidence interval [CI], 1.02-2.15). Note that the highest risk of contracting incidental TB was in the first two years following a diagnosis of AAV, with a nearly 1-fold increase in risk (adjusted HR, 1.91; 95% CI, 1.01-3.60). Female AAV patients were 3.24× more likely than females without AAV to develop TB (adjusted HR 3.24; 95% CI, 1.85-5.67). Conclusions: Patients with AAV exhibit a 48% elevated TB risk, notably, a 91% increase within the first two years postdiagnosis. Female AAV patients face a 3.24 times higher TB risk compared to females without AAV. This study is limited by potential misclassification and overestimation of AAV cases. Clinicians should closely monitor TB risk in AAV patients, especially in females and the initial two years following diagnosis.

Characterization and verification of MMP family members as potential biomarkers in kidney clear cell renal carcinoma.

Renal cell carcinoma can arise from lesions in the renal epithelium. This particular type of cancer is prevalent in the realm of renal cancers and is associated with an unfavorable prognosis. Among these cases, over 70% are classified as kidney renal clear cell carcinoma (KIRC). Since the underlying causes of KIRC haven't been fully understood, there is an urgent need for deeper investigation into its pathogenesis. Various tools, software, and molecular analysis was used, including Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Cytoscape, University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), muTarget, Gene Expression Profiling Interactive Analysis (GEPIA), OncoDB, Human Protein Atlas (HPA), cBioPortal, Kaplan-Meier (KM) plotter, Gene Set Enrichment Analysis (GSEA), Tumor IMmune Estimation Resource (TIMER), Encyclopedia of RNA Interactomes (ENCORI), DrugBank, Encyclopedia of RNA Interactomes (RT-qPCR), targeted bisulfide sequencing (bisulfide-seq), and receiver operating curve (ROC) to matrix metallopeptidase (MMP) gene family constituents, with the precise objective of identifying a small set of hub genes. These hub genes hold the potential to be harnessed as molecular biomarkers for KIRC. By performing STRING and CytoHubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP14 (matrix metallopeptidase 14), and MMP16 (matrix metallopeptidase 16) were recognized as hub genes having highest degree scores. After conducting an in-depth expression analysis of MMP2, MMP9, MMP14, and MMP16 using various The Cancer Genome Atlas (TCGA) databases and RT-qPCR techniques, these displayed a significant increase in expression at both the mRNA and protein levels within KIRC samples when compared to control samples. The impact of the over expression of MMP2, MMP9, MMP14, and MMP16 also left a distinct mark on the worst overall survival (OS) rates of KIRC patients. Furthermore, a targeted bisulfide-seq investigation unveiled a correlation between promoter hypomethylation patterns and the up-regulation of these key genes in KIRC patients. Additionally, hub genes were involved in various diverse oncogenic pathways. In conclusion, four MMP gene family members, including MMP2, MMP9, MMP14, and MMP16 may serve as therapeutic target and molecular biomarker in KIRC.

The discovery of promising candidate biomarkers in kidney renal clear cell carcinoma: evidence from the in-depth analysis of high-throughput data.

Kidney renal clear cell carcinoma (KIRC) is the most prevalent subtype of renal tumor. The underlying mechanisms governing KIRC initiation and progression are less known. The present study aimed to reveal novel hub genes associated with the initiation and progression of KIRC, which may be utilized as novel molecular biomarkers and therapeutic targets for the treatment of KIRC. The GSE6344 dataset from the Gene Expression Omnibus (GEO) database was integrated to identify differentially expressed genes (DEGs) using the limma package. Then, hub genes were identified and UALCAN, GEPIA, OncoDB, DriverDBv3, GENT2, and HPA databases were employed for the expression, survival, and methylation analyses. cBioPortal tool was used to investigate the genetic alterations, while CancerSEA, TIMER, DAVID, ENCORI, DrugBank, and GSCAlite were utilized to explore a few more hub gene-associated parameters. Finally, targeted bisulfite sequencing (bisulfite-seq), and RT-qPCR techniques were used to validate the expression and methylation level of the hub genes using Human RCC cell line 786-O, A-498, and normal renal tubular epithelial cell line HK-2. In total, 7299 DEGs were found between KIRC and normal samples in the GSE6344 dataset. Using STRING and Cytohubba analysis, four hub genes including VEGFA (vascular endothelial growth factor), ALB (Albumin), ENO2 (enolase 2), and CAVI1 (Caveolin 1) were selected as the hub genes. Further, it was validated through extensive analysis of TCGA datasets that these VEGA, ENO2, and CAV1 hub genes were significantly up-regulated, while ALB was significantly down-regulated in KIRC samples compared to controls. The dysregulation of these genes was found to be associated with the overall survival (OS) of the KIRC patients. Moreover, this study also revealed some novel links between VEGA, ALB, ENO2, and CAV1 expression and genetic alterations, promoter methylation status, immune cell infiltration, miRNAs, gene enrichment terms, and various chemotherapeutic drugs. The present study revealed a panel of four hub genes, which contributed to improving our understanding of the underlying molecular mechanisms of KIRC development and can be utilized as promising novel biomarkers for KIRC diagnosis, prognosis, and treatment.

Molecular programs of regional specification and neural stem cell fate progression in macaque telencephalon.

During early telencephalic development, intricate processes of regional patterning and neural stem cell (NSC) fate specification take place. However, our understanding of these processes in primates, including both conserved and species-specific features, remains limited. Here, we profiled 761,529 single-cell transcriptomes from multiple regions of the prenatal macaque telencephalon. We deciphered the molecular programs of the early organizing centers and their cross-talk with NSCs, revealing primate-biased galanin-like peptide (GALP) signaling in the anteroventral telencephalon. Regional transcriptomic variations were observed along the frontotemporal axis during early stages of neocortical NSC progression and in neurons and astrocytes. Additionally, we found that genes associated with neuropsychiatric disorders and brain cancer risk might play critical roles in the early telencephalic organizers and during NSC progression.

Chemical recycling of polyolefins: a closed-loop cycle of waste to olefins.

The unsuitable disposal of plastic wastes has caused serious environmental pollution, and finding a green manner to address this problem has aroused wide concern. Plastic wastes, especially polyolefin wastes, are rich in carbon and hydrogen, and chemical recycling shows distinct advantages in their conversion into olefins and realizes a closed-loop cycling of plastic wastes. Plastic wastes should be labeled before disposal. The necessity for, and methods of, pretreatment are introduced in this paper and the whole recycling process of polyolefin wastes is also summarized. As the core technology pyrolysis, including thermal, catalytic and solvolysis processes, is introduced in detail due to its potential for future development. We also briefly describe the feasible strategies of pyrolytic oil refining and life cycle assessment of the chemical recycling process. In addition, suggestions and perspectives concerning the industrial improvement of polyolefin chemical recycling are proposed.

VEGF-C promotes brain-derived fluid drainage, confers neuroprotection, and improves stroke outcomes.

Meningeal lymphatic vessels promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelium growth factor-C (VEGF-C) is essential for meningeal lymphatic development and maintenance and has therapeutic potential for treating neurological disorders, including ischemic stroke. We have investigated the effects of VEGF-C overexpression on brain fluid drainage, single cell transcriptome in the brain, and stroke outcomes in adult mice. Intra-cerebrospinal fluid administration of an adeno-associated virus expressing VEGF-C (AAV-VEGF-C) increases the CNS lymphatic network. Post-contrast T1 mapping of the head and neck showed that deep cervical lymph node size and drainage of CNS-derived fluids were increased. Single nuclei RNA sequencing revealed a neuro-supportive role of VEGF-C via upregulation of calcium and brain-derived neurotrophic factor (BDNF) signaling pathways in brain cells. In a mouse model of ischemic stroke, AAV-VEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage. AAV-VEGF-C thus promotes CNS-derived fluid and solute drainage, confers neuroprotection, and reduces ischemic stroke damage. Short abstract: Intrathecal delivery of VEGF-C increases the lymphatic drainage of brain-derived fluids confers neuroprotection, and improves neurological outcomes after ischemic stroke.

Cycloartenyl ferulate improves natural killer (NK) cell immunity against cancer by binding to IFNγ receptor 1.

Cycloartenyl ferulate (CF) is abundant in brown rice with multiple biologic functions. It has been reported to possess antitumor activity; however, the related mechanism of action of CF has not been clarified. Herein, we unexpectedly uncover the immunological regulation effects of CF and its molecular mechanism. We discovered that CF directly enhanced the killing capacity of natural killer (NK) cells for various cancer cells in vitro. In vivo, CF also improved cancer surveillance in mouse models of lymphoma clearance and metastatic melanoma dependent on NK cells. In addition, CF promoted anticancer efficacy of the anti-PD1 antibody with improvement of tumor immune microenvironment. Mechanistically, we first unveiled that CF acted on the canonical JAK1/2-STAT1 signaling pathway to enhance the immunity of the NK cells by selectively binding to interferon γ receptor 1. Collectively, our results indicate that CF is a promising immunoregulation agent worthy of attention in clinical application in the future. Due to broad biological significance of interferon γ, our findings also provide a capability to understand the diverse functions of CF.

Physiologically based pharmacokinetic modeling to assess the drug-drug interactions of anaprazole with clarithromycin and amoxicillin in patients undergoing eradication therapy of H. pylori infection.

OBJECTIVE: This study aimed to assess the pharmacokinetic (PK) interactions of anaprazole, clarithromycin, and amoxicillin using physiologically based pharmacokinetic (PBPK) models. METHODS: The PBPK models for anaprazole, clarithromycin, and amoxicillin were constructed using the GastroPlus™ software (Version 9.7) based on the physicochemical data and PK parameters obtained from literature, then were optimized and validated in healthy subjects to predict the plasma concentration-time profiles of these three drugs and assess the predictive performance of each model. According to the analysis of the properties of each drug, the developed and validated models were applied to evaluate potential drug-drug interactions (DDIs) of anaprazole, clarithromycin, and amoxicillin. RESULTS: The developed PBPK models properly described the pharmacokinetics of anaprazole, clarithromycin, and amoxicillin well, and all predicted PK parameters (Cmax,ss, AUC0-τ,ss) ratios were within 2.0-fold of the observed values. Furthermore, the application of these models to predict the anaprazole-clarithromycin and anaprazole-amoxicillin DDIs demonstrates their good performance, with the predicted DDI Cmax,ss ratios and DDI AUC0-τ,ss ratios within 1.25-fold of the observed values, and all predicted DDI Cmax,ss, and AUC0-τ,ss ratios within 2.0-fold. The simulated results show no need to adjust the dosage when co-administered with anaprazole in patients undergoing eradication therapy of H. pylori infection since the dose remained in the therapeutic range. CONCLUSION: The whole-body PBPK models of anaprazole, clarithromycin, and amoxicillin were built and qualified, which can predict DDIs that are mediated by gastric pH change and inhibition of metabolic enzymes, providing a mechanistic understanding of the DDIs observed in the clinic of clarithromycin, amoxicillin with anaprazole.

A Framework for Analyzing Fraud Risk Warning and Interference Effects by Fusing Multivariate Heterogeneous Data: A Bayesian Belief Network.

In the construction of a telecom-fraud risk warning and intervention-effect prediction model, how to apply multivariate heterogeneous data to the front-end prevention and management of telecommunication network fraud has become one of the focuses of this research. The Bayesian network-based fraud risk warning and intervention model was designed by taking into account existing data accumulation, the related literature, and expert knowledge. The initial structure of the model was improved by utilizing City S as an application example, and a telecom-fraud analysis and warning framework was proposed by incorporating telecom-fraud mapping. After the evaluation in this paper, the model shows that age has a maximum sensitivity of 13.5% to telecom-fraud losses; anti-fraud propaganda can reduce the probability of losses above 300,000 yuan by 2%; and the overall telecom-fraud losses show that more occur in the summer and less occur in the autumn, and that the Double 11 period and other special time points are prominent. The model in this paper has good application value in the real-world field, and the analysis of the early warning framework can provide decision support for the police and the community to identify the groups, locations, and spatial and temporal environments prone to fraud, to combat propaganda and provide a timely warning to stop losses.