Comparative studies of the anti-thrombotic effects of saffron and HongHua based on network pharmacology

Purpose: To investigate the comparative anti-thrombotic effects of saffron and Honghua, and also to explore possible mechanisms in thrombosis based on network pharmacology. Methods: A network pharmacology model was used for bioactive components, targets and pathways for saffron and HongHua via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Genecard, Uniprot and KEGG databases. In animal experiments, 72 rats were randomly divided into 9 groups: normal control group (NC), model control group (MC), crocetin groups (80, 40, 20 mg/kg), hydroxysafflor yellow A(HSYA) groups (80, 40, 20 mg/kg), and aspirin group (40 mg/kg). Using in vitro thrombosis models and an acute blood stasis model in vivo, the anti-thrombotic effects of these treatments on clotting time, hemorheology parameters, Thromboxane B2 (TXB2), plasmin activator inhibitor (PAI), protein C (PC), protein S (PS), and thrombinantithrombin complex (TAT) were determined and comparisons made for saffron and HongHua. Results: Five potential compounds, 16 anti-thrombotic targets and 27 pathways were predicted for saffron, while 22 compounds, 37 disease targets and 35 pathways were found for HongHua (p < 0.05). Pharmacological experiments revealed that crocetin and HSYA had significant effects on thrombus length, thrombus wet/dry mass, whole blood viscosity (WBV), erythrocyte aggregation index (EAI), clotting time and D-dimer for the high and middle groups. Unlike HSYA, crocetin also had significant and dose-dependent effects on PAI, prothrombin fragment 1+2 (F1+2) and PS and had highly significant effects on TXB2 and TAT. Conclusion: This research provides a systematic, comprehensive and comparative analysis of component, target and anti-thrombotic pathways of saffron and HongHua based on network pharmacology, and also shows that saffron has more significant anti-thrombotic effect than HongHua. Keywords: Saffron; HongHua; Network pharmacology; Anti-thrombosis; Network mode

CBSeq: A Channel-level Behavior Sequence For Encrypted Malware Traffic Detection

Machine learning and neural networks have become increasingly popular solutions for encrypted malware traffic detection. They mine and learn complex traffic patterns, enabling detection by fitting boundaries between malware traffic and benign traffic. Compared with signature-based methods, they have higher scalability and flexibility. However, affected by the frequent variants and updates of malware, current methods suffer from a high false positive rate and do not work well for unknown malware traffic detection. It remains a critical task to achieve effective malware traffic detection. In this paper, we introduce CBSeq to address the above problems. CBSeq is a method that constructs a stable traffic representation, behavior sequence, to characterize attacking intent and achieve malware traffic detection. We novelly propose the channels with similar behavior as the detection object and extract side-channel content to construct behavior sequence. Unlike benign activities, the behavior sequences of malware and its variant's traffic exhibit solid internal correlations. Moreover, we design the MSFormer, a powerful Transformer-based multi-sequence fusion classifier. It captures the internal similarity of behavior sequence, thereby distinguishing malware traffic from benign traffic. Our evaluations demonstrate that CBSeq performs effectively in various known malware traffic detection and exhibits superior performance in unknown malware traffic detection, outperforming state-of-the-art methods.Comment: Submitted to IEEE TIF

Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

Explosive growth in the study of microbial epigenetics has revealed a diversity of chemical structures and biological functions of DNA modifications in restriction-modification (R-M) and basic genetic processes. Here, we describe the discovery of shared consensus sequences for two seemingly unrelated DNA modification systems, [superscript 6m]A methylation and phosphorothioation (PT), in which sulfur replaces a nonbridging oxygen in the DNA backbone. Mass spectrometric analysis of DNA from Escherichia coli B7A and Salmonella enterica serovar Cerro 87, strains possessing PT-based R-M genes, revealed d(G[subscript PS] [superscript 6m]A) dinucleotides in the G[subscript PS] [superscript 6m]AAC consensus representing ∼5% of the 1,100 to 1,300 PT-modified d(G[subscript PS] A) motifs per genome, with [superscript 6m]A arising from a yet-to-be-identified methyltransferase. To further explore PT and 6m A in another consensus sequence, G[subscript PS] [superscript 6m]ATC, we engineered a strain of E. coli HST04 to express Dnd genes from Hahella chejuensis KCTC2396 (PT in G[subscript PS] ATC) and Dam methyltransferase from E. coli DH10B ( [superscript 6m] A in G [superscript 6m] ATC). Based on this model, in vitro studies revealed reduced Dam activity in G PS ATC-containing oligonucleotides whereas single-molecule real-time sequencing of HST04 DNA revealed [superscript 6m] A in all 2,058 G[subscript PS] ATC sites (5% of 37,698 total GATC sites). This model system also revealed temperature-sensitive restriction by DndFGH in KCTC2396 and B7A, which was exploited to discover that [superscript 6m] A can substitute for PT to confer resistance to restriction by the DndFGH system. These results point to complex but unappreciated interactions between DNA modification systems and raise the possibility of coevolution of interacting systems to facilitate the function of each

Plasma-catalytic synthesis of ammonia over Ru/BaTiO3-based bimetallic catalysts: Synergistic effect from dual-metal active sites

Plasma-catalytic synthesis of ammonia (NH3) was carried out using BaTiO3 supported Ru-M bimetallic catalysts (Ru-M/BaTiO3, M = Fe, Co and Ni) in a dielectric barrier discharge (DBD) reactor. The NH3 synthesis performance followed the order of Ru-Ni/BaTiO3 > Ru/BaTiO3 > Ru-Co/BaTiO3 > Ru-Fe/BaTiO3, with the highest NH3 concentration (3895 ppm) and energy yield (0.39 g kWh−1) achieved over Ru-Ni/BaTiO3 at 25 W and 10 W, respectively. To gain insights into the physio-chemical properties of the Ru-M/BaTiO3 catalysts, comprehensive catalyst characterizations were performed, including X-ray diffraction, N2 physisorption measurements, X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HRTEM), energy dispersive spectroscopy (EDS), and temperature-programmed desorption of CO2 and N2 (CO2 and N2-TPD). The results indicated that the loading of Ni enhanced the basicity and N2 adsorption capacity of the catalyst, as well as the density of oxygen vacancy (OV) on the BaTiO3 surface, which facilitated the adsorption and activation of N2 on catalyst surface. These effects led to the enhanced NH3 synthesis, as excited N2 could be adsorbed on Ru-Ni/BaTiO3 from plasma region and stepwise hydrogenated to form NHx species and ultimately NH3

Who are the preferential targets for intervention programs related to the female condom among sex workers in Southern China?

The authors used a cluster analysis approach to investigate which female sex workers (FSW) are preferential targets for female condom (FC) intervention programs in southern China. Cross-sectional 6-month (N = 316) and 12-month (N = 217) postintervention surveys of FSW were analyzed. Based on FC attitudes and beliefs, initially suggesting FC use to a partner, practicing insertion, total times ever used, and willingness to use in the future, cluster analysis apportioned women into two clusters, with 50.6% and 58.1% of participants in the likely future FC users group at 6 months and 12 months, respectively. Likely future FC users tended to be from boarding houses, older, currently or previously married, experienced with childbirth, with current multiple sex partners, longer history of sex work, and more unprotected sexual encounters. Focusing FC programs on sectors of the community with more FSW who are likely to use FC may be more costeffective for enhancing FC acceptability and usage. © 2013 The Guilford Press

Monounsaturated and polyunsaturated fatty acids concerning prediabetes and type 2 diabetes mellitus risk among participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to March 2020

ObjectiveUnsaturated fatty acids (UFA) may be related to glycometabolism. While associations between UFA intake (especially their subtype) and prediabetes or type 2 diabetes mellitus (T2DM) need to be further studied. In this study, we aimed to evaluate the potential relation of UFA with prediabetes and T2DM.MethodsA total of 16,290 adults aged older than 18 years from the National Health and Nutrition Examination Survey (NHANES) from 2005 to March 2020 were included in the present analysis. Dietary intake was assessed by two day, 24-hour dietary recalls and daily intake of total monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA); four specific fatty acids of MUFA and seven specific fatty acids of PUFA were calculated. Prediabetes and T2DM were diagnosed by fasting glucose, glycohemoglobin, and self-reported medication or insulin. Rao–Scott modified chi-square tests, the Taylor series linearization method, and multivariable logistic regression analyses were applied to analyze the associations of dietary MUFA and PUFA intake with diabetes risk.ResultsOf the participants, 44.34% had prediabetes and 13.16% had T2DM patients. From multivariate analysis, we found that intake of MUFA, PUFA, and some subtypes was negatively associated with the risk of prediabetes and T2DM in Americans. Compared with adults in the lowest tertile, those in the highest MUFA (PUFA) tertile had an approximately 50% (49%) and 69% (68%) lower risk of prediabetes and T2DM, respectively. Moreover, the effects of the subtypes of MUFA and PUFA on prediabetes and T2DM were different. Higher intakes of MFA 18:1, MFA 20:1, PFA 18:2, and PFA 18:3 and higher tertile intakes of MFA 16:1 and PFA 20:4 were related to a lower risk of prediabetes and T2DM. Similarly, the effects of MUFA, PUFA, and subtype on prediabetes and T2DM varied among different age groups, being weakened along with age.ConclusionOur study suggested that total MUFA and PUFA intake might be essential in preventing prediabetes and T2DM, especially in Americans. However, this protective effect may decrease with age. Moreover, the effects of the specific UFA on prediabetes and T2DM need further consideration

Exploring the Protective Effects and Mechanism of Crocetin From Saffron Against NAFLD by Network Pharmacology and Experimental Validation

Background: Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem but no drug has been approved for its treatment. Animal experiments and clinical trials have demonstrated the beneficial of saffron on NAFLD. However, the bioactive ingredients and therapeutic targets of saffron on NAFLD are unclear.Purpose: This study aimed to identify the bioactive ingredients of saffron responsible for its effects on NAFLD and explore its therapy targets through network pharmacology combined with experimental tests.Methods: Various network databases were searched to identify bioactive ingredients of saffron and identify NAFLD-related targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted to enrich functions and molecular pathways of common targets and the STRING database was used to establish a protein-protein interaction network (PPI). The effect of crocetin (CCT) on NAFLD was evaluated in a mouse model of NAFLD by measuring the biomarkers of lipid, liver and renal function, oxidative stress, and inflammation. Liver histopathology was performed to evaluate liver injury. Nuclear factor erythroid-related factor (Nrf2) and hemeoxygenase-1 (HO-1) were examined to elucidate underlying mechanism for the protective effect of saffron against NAFLD.Results: A total of nine bioactive ingredients of saffron, including CCT, with 206 common targets showed therapeutic effects on NAFLD. Oxidative stress and diabetes related signaling pathways were identified as the critical signaling pathways mediating the therapeutic effects of the active bioactive ingredients on NAFLD. Treatment with CCT significantly reduced the activities of aspartate aminotransferase (AST), alanine transaminase (ALT), and the levels of total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), blood urea nitrogen (BUN), creatinine (CR), and uric acid (UA). CCT significantly increased the activities of superoxide dismutase (SOD), and catalase (CAT). Histological analysis showed that CCT suppressed high-fat diet (HFD) induced fat accumulation, steatohepatitis, and renal dysfunctions. Results of ELISA assay showed that CCT decreased the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and increased the expression of HO-1 and Nrf2.Conclusion: This study shows that CCT is a potential bioactive ingredient of saffron that treats NAFLD. Its mechanism of action involves suppressing of oxidative stress, mitigating inflammation, and upregulating Nrf2 and HO-1 expression

Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients

Background and Aims: Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI). Methods: Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis. Results: In the derivation cohort (n=3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR=1.014, 95% CI: 1.005-1.023), baseline ALT (HR=1.014, 95% CI: 1.003-1.024), haemoglobin (HR=1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR=1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n=1497) of which 85 (5.7%) developed ATDILI. Age (HR=1.029, 95% CI: 1.003-1.056), baseline AST (HR=1.036, 95% CI: 1.010-1.062), previous TB treatment (HR=3.894, 95% CI: 1.304-11.625) and active drinking (HR=3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice. Conclusion: Elevation of ALT of ≥3×ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients

Successful treatment with tislelizumab plus chemotherapy for SMARCA4-deficient undifferentiated tumor: a case report

SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) is a devastating subtype of thoracic tumor with SMARCA4 inactivation and is characterized by rapid progression, poor prognosis, and high risk of postoperative recurrence. However, effective treatments for SMARCA4-dUT are lacking. Herein, we describe a patient with SMARCA4-dUT who exhibited an impressive response to the anti-programmed cell death protein-1 (PD-1) antibody (tislelizumab) in combination with conventional chemotherapy (etoposide and cisplatin). To the best of our knowledge, this is the first case of SMARCA4-dUT treated with chemotherapy, comprising etoposide and cisplatin, combined with anti-PD-1 inhibitors. Immunotherapy combined with etoposide and cisplatin may be a promising strategy to treat SMARCA4-dUT