ABSTRACT
Considering the interference of the complexity of underground environment to the bioremediation scheme, an evaluation model for bioremediation technology in the soil source area of oil contaminated sites was established. On the basis of traditional CDE model, a compartment model was coupled to express the adsorption and degradation process, and the spatial expression of biodegradation was enriched through environment-dependent factors. The visualization of the model was achieved based on COMSOL Multiphysics software platform. Two sets of indoor sandbox experiments on natural attenuation and bioaugmentation were carried out for 120 days to verify the prediction function of the model. The results showed that bioaugmentation greatly improved the remediation effect. Petroleum hydrocarbons with different occurrence states exhibited different spatial distributions under the influence of environmental factors. The prediction accuracy evaluation results of total petroleum hydrocarbons, bio available hydrocarbons and non extractable hydrocarbons showed excellent fitting degree, and the model had a good prediction function for petroleum hydrocarbon in soil under different bioremediation scenarios. This model can be used to screen bioremediation technical schemes, prevent pollution and assess risk of petroleum hydrocarbon contaminated sites.
Subject(s)
Petroleum , Soil Pollutants , Biodegradation, Environmental , Petroleum/metabolism , Soil , Soil Pollutants/analysis , Soil Microbiology , Hydrocarbons/metabolismABSTRACT
This study aimed to explore the possible mechanisms of Ling Gui Zhu Gan decoction (LGZGD) in the treatment of nephrotic syndrome (NS) using network pharmacology combined with molecular docking and molecular dynamics simulation. The active ingredients of LGZGD and their targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Swiss Target Prediction database. The NS targets were retrieved from Genecards, OMIM and Drugbank databases. Next, the intersecting targets of drug and disease were imported into the String database for protein-protein interaction network analysis, and the core targets were identified through topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed in the Metascape platform. Finally, molecular docking and molecular dynamics simulation were performed for further validation. The network analysis showed that 109 active ingredients of LGZGD were associated with 105 targets in NS. The key active ingredients (quercetin, kaempferol, naringenin, licochalcone A, formononetin, beta-sitosterol) and the core targets (IL6, AKT1, TNF, VEGFA, TP53, JUN, IL1B, CASP3, EGFR, and STAT3) were further identified. Enrichment analysis indicated that multiple biological processes and pathways, including AGE-RAGE, PI3K-Akt, JAK-STAT, and HIF-1 signaling pathways, might be regulated by LGZGD in the treatment of NS. Molecular docking and molecular dynamics simulation results further indicated that the key active ingredients of LGZGD could stably bind to the core targets through hydrogen bonding and hydrophobic interaction. This study demonstrates that the active ingredients of LGZGD may regulate multiple targets, biological processes and signaling pathways in NS. Our findings may provide a theoretical basis for further studies on LGZGD in the treatment of NS.
Subject(s)
Drugs, Chinese Herbal , Nephrotic Syndrome , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Network Pharmacology , Nephrotic Syndrome/drug therapy , Phosphatidylinositol 3-Kinases , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic useABSTRACT
ABSTRACT: T cell exhaustion is the main cause of sepsis-induced immunosuppression and is associated with the poor prognosis. Nicotinamide adenine dinucleotide (NAD + ) is well known for its anti-aging effect, but its role in sepsis-induced T cell exhaustion remains to be elucidated. In the present study, using a classic septic animal model, we found that the levels of NAD + and its downstream molecule, which is sirtuins 1 (SIRT1), in T cells in sepsis were decreased. Supplementation with nicotinamide ribose (NR), the precursor of NAD + , right after cecal ligation and puncture significantly increased the levels of NAD + and SIRT1. Supplementation with NR alleviated the depletion of mononuclear cells and T lymphocytes in spleen in sepsis and increased the levels of CD3 + CD4 + and CD3 + CD8 + T cells. Interestingly, both Th1 and Th2 cells were expanded after NR treatment, but the balance of Th1/Th2 was partly restored. Nicotinamide ribose also inhibited the regulatory T cells expansion and programmed cell death 1 expression in CD4 + T cells in sepsis. In addition, the bacteria load, organ damage (lung, heart, liver, and kidney), and the mortality of septic mice were reduced after NR supplementation. In summary, these results demonstrate the beneficial effect of NR on sepsis and T cell exhaustion, which is associated with NAD + /SIRT1 pathway.
Subject(s)
NAD , Sepsis , Mice , Animals , NAD/metabolism , Sirtuin 1 , T-Cell Exhaustion , Dietary Supplements , Sepsis/drug therapyABSTRACT
The imbalance of atmospheric, terrestrial and aquatic phosphorus budgets remains a research conundrum and global concern. In this work, the uptake, distribution, bioaccumulation and emission of organophosphate esters (OPEs) by clove trees (Syzygium aromaticum), lemon trees (Citrus limon) and cape jasmine trees (Gardenia jasminoides var. fortuniana) was investigated as conduits for phosphorus transfer or sinks and sources. The objective was to assess the role OPEs in soils play as atmospheric phosphorus sources through plant bioaccumulation and emission. Results demonstrated OPEs in experimental soil plots ranging from 0.01 to 81.0 ng g-1 dry weight, were absorbed and transported through plants to the atmosphere. The total emission of OPEs varied greatly from 0.2 to 588.9 pg g-1 L-1 h-1, with a mean of 47.6 pg g-1 L-1 h-1. There was a negative linear relationship between the concentrations of total phosphorus and four OPEs, tri-iso-butyl phosphate, tri-n-butyl phosphate, tris (2-chloroisopropyl) phosphate and tripentyl phosphate. Trimethyl phosphate levels were positively correlated with total nitrogen, and the concentrations of tri-iso-butyl phosphate, tri-n-butyl phosphate, tris (2-chloroisopropyl) phosphate and tripentyl phosphate decreased along with available potassium in leaves after 72 h. There was a significantly positive linear relationship between higher emission concentrations of OPEs and the emission factor of OPEs concentration (F = 4.2, P = 0.002), with lower emissions of OPEs and the bioaccumulation of OPEs in leaves (F = 4.8, P = 0.004). OPEs releases to the atmosphere were enriched in aerosols, and participate in atmospheric chemical reactions like photolysis, thereby affecting the phosphorus balance and cycling in the atmosphere.
Subject(s)
Flame Retardants , Phosphorus , Bioaccumulation , Environmental Monitoring/methods , Flame Retardants/analysis , Esters , Organophosphates , Phosphates , Soil , Atmosphere , ChinaABSTRACT
BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitor is a new class of drugs for treating renal anemia. It is a second-generation hypoxia-inducible factor prolyl hydroxylase-2 (PHD2) inhibitor. Roxadustat can effectively increase hemoglobin in patients with dialysis-dependent chronic kidney disease, with an adverse events profile comparable to that of epoetin alfa. We administered roxadustat to a maintenance hemodialysis patient who was allergic to erythropoiesis-stimulating agents (ESAs) and depended on blood transfusion for five years. After applying Roxadustat, the patient's anemia improved significantly. CASE SUMMARY: A 77-year-old Chinese man had type 2 diabetes for 16 years, underwent maintenance hemodialysis for five years, and had fatigue for five years. Laboratory tests showed severe anemia (hemoglobin concentration of 42 g/L). The patient was administered a subcutaneous injection of ESAs before dialysis. He suffered an allergic shock immediately and fainted. His blood pressure dropped to undetectable levels. He was not administered ESAs henceforth. The patient was prescribed iron supplements and received blood transfusions occasionally for five years. His hemoglobin concentration ranged from 42-68 g/L. After taking six weeks of oral roxadustat three times weekly (100 mg TIW), the patient's hemoglobin concentration increased significantly, and his symptoms decreased. We adjusted the doses of roxadustat, and the hemoglobin concentration was maintained between 97 and 126 g/L. CONCLUSION: Oral roxadustat is effective in treating anemia in maintenance hemodialysis patients who cannot be administered ESAs.
ABSTRACT
Background and objectives: The effect of auricular acupressure (AA) for maintenance hemodialysis (MHD) patients with insomnia has been controversial. This study assessed the efficacy and safety of AA for MHD patients with chronic insomnia. Design, setting, participants, and measurements: This was a multicenter, double-blind (participant and assessor), randomized sham-controlled trial. A total of 133 subjects were randomized to receive AA on active points (AA group, n = 64) or on sham auricular acupressure (SAA) points (SAA group, n = 69) for 8 weeks and followed up for 12 weeks. AA was provided by assigned qualified nurses who were not involved in assessment. The primary outcome was the clinical response rate, which was defined as the percentage of participants who reached a reduction of Pittsburgh Sleep Quality Index (PSQI) global score ≥3 in each group. Secondary outcomes included changes in PSQI scores over time, PSQI scores and hypnotics use at each visit, and changes in the weekly dose of hypnotics for drug-dependent subjects. Results: At week 8, the AA group yielded a higher clinical response rate than the SAA group (AA: 55% vs. SAA: 36%, odds ratio: 1.5, 95% confidence interval: 1.0-2.2, p = 0.033). Both groups showed a reduction in PSQI global scores during treatment and follow-up, compared with the baseline, respectively. A significant change of PSQI global score was observed over time (F = 28.387, p < 0.001). PSQI global score of the AA group was relatively lower than that of the SAA group at each visit (p < 0.05 at week 16 and 20). For those depending on hypnotics, AA reduced their consumption of hypnotics. The intervention was safe, and its adherence was satisfactory. Conclusion: AA could serve as a complementary or alternative therapy for MHD patients with insomnia by improving their sleep quality and reducing their use of hypnotics. Clinical trial registration: Clinicaltrials.gov, Identifier: NCT03015766.
Subject(s)
Acupressure , Sleep Initiation and Maintenance Disorders , Double-Blind Method , Humans , Hypnotics and Sedatives/therapeutic use , Renal Dialysis/adverse effects , Sleep Initiation and Maintenance Disorders/therapyABSTRACT
Vascular endothelial cells play a vital role in atherosclerotic changes and the progression of cardiovascular disease in older adults. Previous studies have indicated that Astragalus polysaccharides (APS), a main active component of the traditional Chinese medicine Astragalus, protect mitochondria and exert an antiaging effect in the mouse liver and brain. However, the effect of APS on rat aortic endothelial cell (RAEC) senescence and its underlying mechanism have not been investigated. In this study, we extracted RAECs from 2-month-old male Wistar rats by the tissue explant method and found that APS ameliorated the high-glucose-induced increase in the frequency of SA-ß-Gal positivity and the levels of the senescence-related proteins p16, p21, and p53. APS increased the tube formation capacity of RAECs under high-glucose conditions. Moreover, APS enhanced the expression of the mitochondrial Na+/Ca2+ exchanger NCLX, and knockdown of NCLX by small interfering RNA (siRNA) transfection suppressed the antiaging effect of APS under high-glucose conditions. Additionally, APS ameliorated RAEC mitochondrial dysfunction, including increasing ATP production, cytochrome C oxidase activity and the oxygen consumption rate (OCR), and inhibited high-glucose-induced NLRP3 inflammasome activation and IL-1ß release, which were reversed by siNCLX. These results indicate that APS reduces high-glucose-induced inflammasome activation and ameliorates mitochondrial dysfunction and senescence in RAECs by modulating NCLX. Additionally, APS enhanced the levels of autophagy-related proteins (LC3B-II/I, Atg7) and increased the quantity of autophagic vacuoles under high-glucose conditions. Therefore, these data demonstrate that APS may reduce vascular endothelial cell inflammation and senescence through NCLX.
Subject(s)
Astragalus Plant , Inflammasomes , Animals , Astragalus Plant/metabolism , Endothelial Cells/metabolism , Glucose/metabolism , Inflammasomes/metabolism , Inflammasomes/pharmacology , Male , Mice , Mitochondria/metabolism , Polysaccharides/pharmacology , RNA, Small Interfering/metabolism , Rats , Rats, Wistar , Sodium-Calcium Exchanger/metabolismABSTRACT
The current detoxification options of uranium, a toxic radioactive heavy metal, have obvious side effects. Polygonatum kingianum (PK), a natural product with the function of antioxidant, may be effective in detoxification and prevention of uranium-induced nephrotoxicity. Here, we studied the protective effects of PK polysaccharides (PKP) and aqueous extract (PKAE) on uranium-induced toxicity in human kidney (HK-2) cells. First, the physicochemical properties of PKP and PKAE were characterized. Assays on cultured cells demonstrated that pretreatment with PKP and PKAE significantly increased metabolic activity, relieved morphological impairments, and alleviated apoptosis. The impairments caused by uranium exposure were ameliorated (mitochondrial membrane potential and ATP level increased while reactive oxygen species decreased). Molecular mechanistic studies revealed that PKP and PKAE alleviated uranium-induced cytotoxicity by regulating mitochondria-mediated apoptosis and the GSK-3ß/Fyn/Nrf2 pathway. Collectively, our data support the preventive and therapeutic applications of PKP and PKAE for uranium poisoning.
Subject(s)
Polygonatum , Uranium , Apoptosis , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Kidney , Oxidative Stress , Polygonatum/chemistry , Polysaccharides/metabolism , Polysaccharides/pharmacology , Reactive Oxygen Species/metabolism , Uranium/toxicityABSTRACT
BACKGROUND: Tailoring warfarin use poses a challenge for physicians and pharmacists due to its narrow therapeutic window and substantial inter-individual variability. This study aimed to create an adapted neural-fuzzy inference system (ANFIS) model using preprocessed balance data to improve the predictive accuracy of warfarin maintenance dosing in Chinese patients undergoing heart valve replacement (HVR). METHODS: This retrospective study enrolled patients who underwent HVR between June 1, 2012, and June 1, 2016, from 35 centers in China. The primary outcomes were the mean difference between predicted warfarin dose by ANFIS models and actual dose and the models' predictive accuracy, including the ideal predicted percentage, the mean absolute error (MAE), and the mean squared error (MSE). The eligible cases were divided into training, internal validation, and external validation groups. We explored input variables by univariate analysis of a general linear model and created two ANFIS models using imbalanced and balanced training sets. We finally compared the primary outcomes between the imbalanced and balanced ANFIS models in both internal and external validation sets. Stratified analyses were conducted across warfarin doses (low, medium, and high doses). RESULTS: A total of 15,108 patients were included and grouped as follows: 12,086 in the imbalanced training set; 2820 in the balanced training set; 1511 in the internal validation set; and 1511 in the external validation set. Eight variables were explored as predictors related to warfarin maintenance doses, and imbalanced and balanced ANFIS models with multi-fuzzy rules were developed. The results showed a low mean difference between predicted and actual doses (< 0.3 mg/d for each model) and an accurate prediction property in both the imbalanced model (ideal prediction percentage, 74.39-78.16%; MAE, 0.37 mg/daily; MSE, 0.39 mg/daily) and the balanced model (ideal prediction percentage, 73.46-75.31%; MAE, 0.42 mg/daily; MSE, 0.43 mg/daily). Compared to the imbalanced model, the balanced model had a significantly higher prediction accuracy in the low-dose (14.46% vs. 3.01%; P < 0.001) and the high-dose warfarin groups (34.71% vs. 23.14%; P = 0.047). The results from the external validation cohort confirmed this finding. CONCLUSIONS: The ANFIS model can accurately predict the warfarin maintenance dose in patients after HVR. Through data preprocessing, the balanced model contributed to improved prediction ability in the low- and high-dose warfarin groups.
Subject(s)
Anticoagulants , Warfarin , Algorithms , Anticoagulants/adverse effects , Heart Valves , Humans , Retrospective StudiesABSTRACT
Patients requiring low-dose warfarin are more likely to suffer bleeding due to overdose. The goal of this work is to improve the feedforward neural network model's precision in predicting the low maintenance dose for Chinese in the aspect of training data construction. We built the model from a resampled dataset created by equal stratified sampling (maintaining the same sample number in three dose-groups with a total of 3639) and performed internal and external validations. Comparing to the model trained from the raw dataset of 19,060 eligible cases, we improved the low-dose group's ideal prediction percentage from 0.7 to 9.6% and maintained the overall performance (76.4% vs. 75.6%) in external validation. We further built neural network models on single-dose subsets to invest whether the subsets samples were sufficient and whether the selected factors were appropriate. The training set sizes were 1340 and 1478 for the low and high dose subsets; the corresponding ideal prediction percentages were 70.2% and 75.1%. The training set size for the intermediate dose varied and was 1553, 6214, and 12,429; the corresponding ideal prediction percentages were 95.6, 95.1%, and 95.3%. Our conclusion is that equal stratified sampling can be a considerable alternative approach in training data construction to build drug dosing models in the clinic.
Subject(s)
Anticoagulants/administration & dosage , Heart Valve Diseases/surgery , Heart Valves/drug effects , Warfarin/administration & dosage , Adult , Aged , Cardiac Surgical Procedures/adverse effects , China/epidemiology , Dose-Response Relationship, Drug , Female , Heart Valve Diseases/drug therapy , Heart Valve Diseases/pathology , Heart Valve Prosthesis , Heart Valves/physiopathology , Heart Valves/surgery , Humans , Machine Learning , Male , Middle Aged , Neural Networks, ComputerABSTRACT
BACKGROUND: Due to the diversity of the ingredients, the complexity of the mechanism of action, the uncertainty of the effective ingredients, coupled with the multiple species and multiple growing areas, the quality control (QC) of Traditional Chinese Medicines (TCMs) is challenging. Discovering and identifying effective compounds from the complex extracts of TCMs and then establishing a scientific QC method is the key to the holistic QC of TCMs. PURPOSE: To develop an anti-lung-cancer-guided spectrum-effect relationship approach for the discovery of QC markers of the rhizome of Curcuma wenyujin (WEZ) and establish a bioactive compounds-based holistic QC method. METHODS: The chemical profiling of the volatile oil (WVO) from 42 batches of WEZ collected from different growing areas was performed by GC-MS. The anti-lung cancer activity of different WVO samples was determined by CCK-8 assay against human lung cancer cells (A549). The apoptosis and cell cycle analysis under different concentrations of WVO were detected by flow cytometry. SIMCA-P software was used to perform multivariate statistical analysis on the chemical composition of different WVO samples and to find the different components. Active compounds were screened using a PLSR model of the spectrum-effect relationship. Bioactive compounds-based fingerprint and quantification of the leading bioactive compounds were developed by GC-MS and GC-FID, respectively. RESULTS: Seventy-eight compounds were detected in WVO and 54 were successfully identified. The multivariate statistical analysis uncovered that WVO components and the anti-A549 activity of WVO at the concentration of 60 nl/ml differ greatly according to the origin of the plant. The WVO at the concentration of 60 nl/ml (IC50) increased A549 cells apoptosis significantly with late and early apoptosis of 15.61% and 7.80%, and the number of cells in the G2/M phase were also increased significantly under this concentration. The spectrum-effect relationship analysis revealed that 44 compounds were positively correlated with their activities, and the result was verified by A549 cell viability assay. Sixteen positively correlated compounds were further selected as QC markers according to their relative amount > 0.5% and anticancer activity. Finally, the 16 QC markers-based GC-MS fingerprint was established to holistically control the quality of WEZ, and a GC-FID method was developed for the quantification of leading bioactive compounds, ß-elemene and ß-caryophyllene. CONCLUSION: Based on an anti-lung-cancer-guided spectrum-effect relationship approach, the bioactive compounds-based holistic QC method was successfully developed for WEZ, which could provide a valuable reference for the QC of TCMs.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Biomarkers/analysis , Curcuma/chemistry , Drugs, Chinese Herbal/chemistry , A549 Cells , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Biomarkers/chemistry , Drugs, Chinese Herbal/pharmacology , Gas Chromatography-Mass Spectrometry/methods , Humans , Oils, Volatile/chemistry , Polycyclic Sesquiterpenes/analysis , Polycyclic Sesquiterpenes/pharmacology , Quality Control , Rhizome/chemistry , Sesquiterpenes/analysis , Sesquiterpenes/pharmacologyABSTRACT
Cardiorenal syndrome type 3 (CRS-3) is damage to the heart following acute kidney injury (AKI). Although many experiments have found that inflammation, oxidative stress, and cardiomyocyte death are involved in cardiomyocyte pathophysiological alterations during CRS-3, they lack a non-bias analysis to figure out the primary mediator of cardiac dysfunction. Herein proteomic analysis was operated in CRS-3 and growth factor receptor-bound protein 2 (Grb2) was identified as a regulator involving AKI-related myocardial damage. Increased Grb2 was associated with cardiac diastolic dysfunction and mitochondrial bioenergetics impairment; these pathological changes could be reversed through the administration of a Grb2-specific inhibitor during AKI. Molecular investigation illustrated that augmented Grb2 promoted cardiomyocyte mitochondrial metabolism disorder through inhibiting the Akt/mTOR signaling pathway. Besides that, Mouse Inflammation Array Q1 further identified IL-6 as the upstream stimulator of Grb2 upregulation after AKI. Exogenous administration of IL-6 induced cardiomyocyte damage and mitochondrial bioenergetics impairment, whereas these effects were nullified in cardiomyocytes pretreated with Grb2 inhibitor. Our results altogether identify CRS-3 to be caused by the upregulations of IL-6/Grb2 which contribute to cardiac dysfunction through inhibiting the Akt/mTOR signaling pathway and inducing cardiomyocyte mitochondrial bioenergetics impairment. This finding provides a potential target for the clinical treatment of patients with CRS-3.
ABSTRACT
We aimed to elucidate the role of cortical and hippocampal dendritic spines on neurological deficits associated with hippocampal microgliosis, hippocampal neurogenesis, and neuroinflammation in mice with cortical compact impact (CCI) injury. In the present study, we found that CCI reduced spatial memory mean latency (10 s. vs 50 s) and motor dysfunction (130 s. vs 150 s.) in mice, as determined by Morris water maze and rotarod test, respectively. Golgi staining of cortical pyramidal neurons revealed that, compared to the controls, the CCI group treated with vehicle solution had significantly lower values of dendritic order (or dendritic branch number) (4.0 vs 6.2), total spine length (400 µm vs 620 µm) and spine density (40 spines/µm vs 60 spines/µm), but had significantly higher values of dendritic beading (40 beadings/mm vs 20 beadings/mm). Additionally, Sholl analysis showed that, compared to controls, the CCI + NS group mice had significantly lower values of dendritic intersections (1.0 vs 2.0). Immunofluorescence assay also revealed that, compared to controls, the CCI + NS group mice had significantly higher values of the newly formed hippocampal cells (1250/mm2 vs 1000/mm2) but significantly lower values of dendritic order (2.0 branch # vs 4.2 branch #), total spine length (180 µm vs 320 µm) and intersection (1.0 vs 3.0). The CCI + NS group mice further showed significantly higher numbers of microglia in the dentate gyrus of the hippocampus and higher concentrations of pro-inflammatory cytokines in the cerebrospinal fluids. All the CCI-induced spatial memory (40 s) and motor (150 s) dysfunction, deranged dendritic and spine morphology of cortical pyramidal neurons or hippocampal newly formed cells, hippocampal microgliosis, and central neuroinflammation were all significantly reduced by melatonin administration during post-CCI. Simultaneously, melatonin therapy caused an enhancement in the compensatory hippocampal neurogenesis and neurotrophic growth factors (e.g., doublecortin-1) and compensatory central anti-inflammatory cytokines. Our results indicate that melatonin attenuates the spatial memory and motor deficits via the modification of cortical and hippocampal dendritic spine morphology, hippocampal microgliosis and neurogenesis, and neuroinflammation in mice with traumatic brain injury.
Subject(s)
Brain Injuries, Traumatic/drug therapy , Dendritic Spines/drug effects , Hippocampus/drug effects , Melatonin/pharmacology , Motor Cortex/drug effects , Neurons/drug effects , Spatial Memory/drug effects , Animals , Disease Models, Animal , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND AND OBJECTIVE: Because of the narrow therapeutic window and huge inter-individual variation, the individual precision on anticoagulant therapy of warfarin is challenging. In our study, we aimed to construct a Back Propagation Neural Network (BPNN) model to predict the individual warfarin maintenance dose among Chinese patients who have undergone heart valve replacement, and validate its prediction accuracy. METHODS: In this study, we analyzed 13,639 eligible patients extracted from the Chinese Low Intensity Anticoagulant Therapy after Heart Valve Replacement database, which collected data on patients using warfarin after heart valve replacement from 15 centers all over China. Ten percent of patients who were finally enrolled in the database were used as the external validation, while the remaining were randomly divided into the training and internal validation groups at a ratio of 3:1. Input variables were selected by univariate analysis of the general linear model; 2.0, the mean value of the international normalized ratio (INR) range 1.5-2.5, was used as the mandatory variable. The BPNN model and the multiple linear regression (MLR) model were constructed by the training group and validated through comparisons of the mean absolute error (MAE), mean squared error (MSE), root mean squared error (RMSE), and ideal predicted percentage. RESULTS: Finally, 10 input variables were selected and a three-layer BPNN model was constructed. In the BPNN model, the value of MAE (0.688 mg/day and 0.740 mg/day in internal and external validation, respectively), MSE (0.580 mg/day and 0.599 mg/day in internal and external validation, respectively), and RMSE (0.761 mg/day and 0.774 mg/day in internal and external validation, respectively) were achieved. Ideal predicted percentages were high in both internal (63.0%) and external validation (59.7%), respectively. Compared with the MLR model, the BPNN model showed a higher ideal prediction percentage in the external validation group (59.7% vs. 56.6%), and showed the best prediction accuracy in the intermediate-dose subgroup (internal validation group: 85.2%; external validation group: 84.7%) and a high predicted percentage in the high-dose subgroup (internal validation group: 36.2%; external validation group: 39.8%), but poor performance in the low-dose subgroup (internal validation group: 0%; external validation group: 0.3%). Meanwhile, the BPNN model showed better ideal prediction percentage in the high-dose group than the MLR model (internal validation: 36.2% vs. 31.6%; external validation: 42.8% vs. 37.8%). CONCLUSION: The BPNN model shows promise for predicting the warfarin maintenance dose after heart valve replacement.
Subject(s)
Anticoagulants/administration & dosage , Heart Valve Prosthesis Implantation , Warfarin/administration & dosage , Adult , Algorithms , Asian People , China , Female , Heart Valves/surgery , Humans , International Normalized Ratio , Male , Middle Aged , Warfarin/therapeutic useABSTRACT
The emission and deposition of global atmospheric phosphorus (P) have long been considered unbalanced, and primary biogenic aerosol particles (PBAP) and phosphine (PH3) are considered to be the only atmospheric P sources from the ecosystem. In this work, we found and quantified volatile organic phosphorus (VOP) emissions from plants unaccounted for in previous studies. In a greenhouse in which lemons were cultivated, the atmospheric total phosphorus (TP) concentration of particulate matter (PM) was 41.8% higher than that in a greenhouse containing only soil, and the proportion of organic phosphorus (OP) in TP was doubled. 31P nuclear magnetic resonance tests (31P-NMR) of PM showed that phosphate monoesters were the main components contributed by plants in both the greenhouse and at an outside observation site. Atmospheric gaseous P was directly measured to be 1-2 orders of magnitude lower than P in PM but appeared to double during plant growing seasons relative to other months. Bag-sampling and gas chromatography mass spectrometry (GCMS) tests showed that the gaseous P emitted by plants in the greenhouse was triethyl phosphate. VOP might be an important component of atmospheric P that has been underestimated in previous studies.
Subject(s)
Particulate Matter/analysis , Phosphorus/analysis , Plants/metabolism , Soil/chemistryABSTRACT
This study investigated the reactions among CO32-, PO43-, NH4+, Mg2+, and Ca2+, under different CO32- concentration and Mg2+/Ca2+ ratio, and conducted sludge anaerobic digestion (AD) with silicate addition to achieve in-situ CO2 sequestration and nutrients removal. High CO32- concentration facilitated the formation of MgNH4PO4, and Mg2+/Ca2+ ratio of 1:1 achieved best CO32-, PO43-, and NH4+ removal in simulated anaerobic digestate. Supplementation of 40â¯g/L magnesium silicate combined with 20â¯g/L wollastonite decreased CO2 content in biogas from 28.2% to 19.0%, and removed PO43- and NH4+ by 61.8% and 21.2%, respectively, in AD. Simultaneous in-situ CO2 sequestration and nutrients removal was achieved by directed precipitation of PO43-, NH4+, and CO2 with silicate released Mg2+ and Ca2+, to form MgNH4PO4 and CaCO3. Meanwhile, methane production was improved by 51.2% with silicate supplementation. This study provides an attractive measure for CO2 and nutrients removal as well as methane production enhancement of sludge AD.
Subject(s)
Carbon Dioxide/metabolism , Nutrients , Silicates/chemistry , Anaerobiosis , Biofuels/analysis , Bioreactors , Methane/metabolism , SewageABSTRACT
A full-scale project of thermal-alkaline pretreatment and alkaline fermentation of sewage sludge was built to produce volatile fatty acids (VFAs) which was then used as external carbon source for improving biological nitrogen and phosphorus removals (BNPR) in wastewater plant. Results showed this project had efficient and stable performances in VFA production, sludge reduce and BNPR. Hydrolysis rate in pretreatment, VFAs yield in fermentation and total VS reduction reached 68.7%, 261.32â¯mg COD/g VSS and 54.19%, respectively. Moreover, fermentation liquid with VFA presented similar efficiency as acetic acid in enhancing BNPR, obtaining removal efficiencies of nitrogen and phosphorus up to 72.39% and 89.65%, respectively. Finally, the project also presented greater economic advantage than traditional processes, and the net profits for VFAs and biogas productions are 9.12 and 3.71â¯USD/m3 sludge, respectively. Long-term operation indicated that anaerobic alkaline fermentation for VFAs production is technically and economically feasible for sludge carbon recovery.
Subject(s)
Fermentation , Wastewater , Bioreactors , Fatty Acids, Volatile , Hydrogen-Ion Concentration , Phosphorus , SewageABSTRACT
BACKGROUND/AIMS: To determine whether an aqueous extract of Trametes robiniophila Murr. (Huaier) suppresses anti-Thy-1 mesangial proliferative glomerulonephritis (MsPGN) in vivo and platelet-derived growth factor (PDGF)-BB-induced mesangial cell proliferation in vitro. METHODS: Male Wistar rats were randomly categorized into 5 groups: Sham, Thy-1, and 3 Huaier-treated groups (low, medium, and high dose). Two weeks after treatment, urinary proteins were quantified and renal pathological changes were examined. MAX interactor 1 (Mxi-1) and proliferating cell nuclear antigen (PCNA) expression levels in isolated glomeruli, rat mesangial cell viability, cell-cycle distribution, and cell-cycle pathways were assessed. RESULTS: Huaier diminished the proliferative damages and urinary protein secretion in Thy-1 rats. PCNA was downregulated, whereas Mxi-1 was upregulated in the isolated glomeruli of Huaier-treated groups compared with the Thy-1 group. Huaier inhibited PDGF-BB- stimulated proliferation of rat mesangial cells in a time- and dose-dependent manner (50% inhibitory concentration = 6.19 mg/mL) and induced G2 cell-cycle arrest. Cell-cycle pathway proteins were downregulated, whereas Mxi-1 was upregulated in Huaier-treated mesangial cells compared with PDGF-BB-stimulated cells. CONCLUSION: Huaier reduces urinary protein excretion and relieves hyperplasia in mesangial cells in anti-Thy-1 MsPGN as well as inhibits PDGF-BB-stimulated proliferation and DNA synthesis of rat mesangial cells in vitro, suggesting its novel therapeutic potential in MsPGN.
Subject(s)
Cell Proliferation/drug effects , Complex Mixtures/pharmacology , Drugs, Chinese Herbal/pharmacology , Isoantibodies/metabolism , Nephritis/pathology , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Becaplermin , CDC2 Protein Kinase/metabolism , Cyclin B1/metabolism , Cyclin-Dependent Kinase 2/metabolism , G2 Phase Cell Cycle Checkpoints/drug effects , Kidney/metabolism , Kidney/pathology , Kidney Glomerulus/cytology , Male , Mesangial Cells/cytology , Mesangial Cells/drug effects , Mesangial Cells/metabolism , Nephritis/metabolism , Proliferating Cell Nuclear Antigen/metabolism , Proto-Oncogene Proteins c-sis/pharmacology , Rats , Rats, Wistar , Trametes , Tumor Suppressor Proteins/metabolism , Up-Regulation/drug effectsABSTRACT
New antimicrobial agents are urgently needed to treat infections caused by drug-resistant pathogens and by pathogens capable of persisting in biofilms. The aim of this study was to identify traditional Chinese herbs that could inhibit biofilm formation of Pseudomonas aeruginosa, an important human pathogen that causes serious and difficult-to-treat infections in humans. A luxCDABE-based reporter system was constructed to monitor the expression of six key biofilm-associated genes in P. aeruginosa. The reporters were used to screen a library of 36 herb extracts for inhibitory properties against these genes. The results obtained indicated that the extract of Herba patriniae displayed significant inhibitory effect on almost all of these biofilm-associated genes. Quantitative analysis showed that H. patriniae extract was able to significantly reduce the biofilm formation and dramatically altered the structure of the mature biofilms of P. aeruginosa. Further studies showed H. patriniae extract decreased exopolysaccharide production by P. aeruginosa and promoted its swarming motility, two features disparately associated with biofilm formation. These results provided a potential mechanism for the use of H. patriniae to treat bacterial infections by traditional Chinese medicines and revealed a promising candidate for exploration of new drugs against P. aeruginosa biofilm-associated infections.
Subject(s)
Biofilms/drug effects , Plant Extracts/administration & dosage , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Humans , Medicine, Chinese Traditional/methods , Patrinia/chemistry , Plant Extracts/chemistry , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/pathogenicityABSTRACT
In order to investigate the scouring and deposition law of pollutants in urban sewer systems, the investigation of sewer systems was carried out in Xi'an. The results showed that the thickness of sediment in the branch pipe and the main pipe varied obviously. At the peak of the drainage, the velocity increased gradually, and the thickness of the pipeline sediment decreased. At the bottom of the drainage trough, the changes of the velocity and the thickness of the pipeline sediment were opposite, with variations of 0-24 mm and 0-12 mm, respectively. And the probability of granular contaminants sedimentation and scouring in sewer systems was high, while the thickness of sediment in sewage main pipe was less than the above mentioned pipes, the variation of which was 0-7 mm. In addition, the sedimentation and scouring in the main pipeline kept relatively balanced and the thickness of sediment remained stable. In order to clarify the relationship between the concentration of pollutants and the flow velocity, a pilot sewer system was established. The effects of different flow rates, which were 0.1, 0.3, 0.6, 0.9, 1.2 m·s-1, respectively, on the contents of carbon (organic), nitrogen and phosphorus in the pipeline were studied. The results showed that with the increase of the flow velocity, the scour intensity increased and the concentration of pollutants in the pipeline also increased sharply. As shown by the monitoring results of the static light scattering particle size analyzer, the carbon organic pollutants in the pipeline were easily adsorbed on the larger particles, while nitrogen and phosphorus pollutants were easily adsorbed on the particles with smaller size. Analysis on the change of the urban sewage pipeline showed, when the flow rate was less than 0.6 m·s-1, the sedimentation of granular pollutants in the sewage was greater than the scouring effect. When the flow velocity was higher than 0.6 m·s-1, the water scouring intensity increased and the scouring action was greater than the sedimentation, meanwhile, the sediments were carried by the water and the thickness of the sediments was reduced. The increase of the organic pollutants in the sewage was bigger than the nitrogen and phosphorus pollutants, so that the existing sewage carbon source was improved.