[Effects of nitrogen fertilizer reduction and biochar application on paddy soil nutrient and nitrogen uptake of rice]. / å‡æ°®é æ–½ç¨»ç§†ç”Ÿç‰©ç‚­å¯¹ç¨»ç”°åœŸå£¤å »åˆ†åŠæ¤æ ªæ°®ç´ å¸æ”¶çš„å½±å“.

We explored the impacts of nitrogen (N) reduction and biochar application on soil fertility and nutrient uptake of rice in early and late seasons of 2018 with a field experiment. There were six treatments, including control (no N application, CK), conventional N application (N100), 20% N reduction (N80), 20% N reduction plus biochar application (N80+BC), 40% N reduction (N60), 40% N reduction plus biochar application (N60+BC). Our results showed that 20% and 40% N reduction and/or with biochar application did not affect soil pH, organic matter, total N, total phosphorous (P), total potassium (K), ammonium N, available P and K in comparison with N100 treatment. N80+BC and N60+BC substantially increased soil cation exchange capacity (CEC) at tillering stage and electrical conductivity (EC) at heading stage in late season, respectively. Compared with the treatment with single N reduction, N80+BC significantly increased soil available K in early and late seasons and soil pH and total N in late season, while N60+BC increased soil total K at mature stage in early season. Soil nitrate content was decreased along with the growth stages for all treatments in early season. Compared with tillering stage, soil nitrate N content in conventional N application at heading stage and mature stage was decreased by 50.0% and 71.6%, respectively. Soil nitrate content in biochar treatment only was decreased by 6.3%-45.5%. N application along with biochar application had no significant effects on plant N uptake and utilization in early season. However, N reduction with biochar application significantly increased plant N uptake and N utilization rate by 34.8%-52.4% in late season, compared to conventional N application and single N reduction. Our findings suggest that adequate N reduction along with biochar application could maintain soil health and improve plant N uptake and utilization efficiency.

Hyperthyroidism in the personalized medicine era: the rise of mathematical optimization.

Thyroid over-activity or hyperthyroidism constitutes a significant morbidity afflicting the world. The current medical practice of dose titration of anti-thyroid drug (ATD) treatment for hyperthyroidism is relatively archaic, being based on arbitrary and time-consuming trending of thyroid function that requires multiple clinic monitoring visits before an optimal dose is found. This prompts a re-examination into more deterministic and efficient treatment approaches in the present personalized medicine era. Our research project seeks to develop a personalized medicine model that facilitates optimal drug dosing via the titration regimen. We analysed 49 patients' data consisting of drug dosage, time period and serum free thyroxine (FT4). Ordinary differential equation modelling was applied to describe the dynamic behaviour of FT4 concentration. With each patient's data, an optimization model was developed to determine parameters of synthesis rate, decay rate and IC50. We derived the closed-form time- and dose-dependent solution which allowed explicit estimates of personalized predicted FT4. Our equation system involving time, drug dosage and FT4 can be solved for any variable provided the values of the other two are known. Compared against actual FT4 data within a tolerance, we demonstrated the feasibility of predicting the FT4 subsequent to any prescribed dose of ATD with favourable accuracy using the initial three to five patient-visits' data respectively. This proposed mathematical model may assist clinicians in rapid determination of optimal ATD doses within allowable prescription limits to achieve any desired FT4 within a specified treatment period to accelerate the attainment of euthyroid targets.

Combination of pharmacophore hypothesis and molecular docking to identify novel inhibitors of HCV NS5B polymerase.

Hepatitis C virus (HCV) infection or HCV-related liver diseases are now shown to cause more than 350,000 deaths every year. Adaptability of HCV genome to vary its composition and the existence of multiple strains makes it more difficult to combat the emergence of drug-resistant HCV infections. Among the HCV polyprotein which has both the structural and non-structural regions, the non-structural protein NS5B RNA-dependent RNA polymerase (RdRP) mainly mediates the catalytic role of RNA replication in conjunction with its viral protein machinery as well as host chaperone proteins. Lack of such RNA-dependent RNA polymerase enzyme in host had made it an attractive and hotly pursued target for drug discovery efforts. Recent drug discovery efforts targeting HCV RdRP have seen success with FDA approval for sofosbuvir as a direct-acting antiviral against HCV infection. However, variations in drug-binding sites induce drug resistance, and therefore targeting allosteric sites could delay the emergence of drug resistance. In this study, we focussed on allosteric thumb site II of the non-structural protein NS5B RNA-dependent RNA polymerase and developed a five-feature pharmacophore hypothesis/model which estimated the experimental activity with a strong correlation of 0.971 & 0.944 for training and test sets, respectively. Further, the Güner-Henry score of 0.6 suggests that the model was able to discern the active and inactive compounds and enrich the true positives during a database search. In this study, database search and molecular docking results supported by experimental HCV viral replication inhibition assays suggested ligands with best fitness to the pharmacophore model dock to the key residues involved in thumbs site II, which inhibited the HCV 1b viral replication in sub-micro-molar range.

T cell immune response is correlated with fibrosis and inflammatory activity in hepatitis B cirrhotics.

AIM: To explore the relationship among interferon-gamma (IFN-gamma) activity, fibrogenesis, T cell immune responses and hepatic inflammatory activity. METHODS: Peripheral blood samples from a total of 43 hepatitis B cirrhotic patients (LC) and 19 healthy controls (NC) were collected to measure their serum levels of IFN-gamma, interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-10 (IL-10) and three serological markers of fibrosis including hyaluronic acid (HA), procollagen type III peptide (PIIIP), and type IV collagen were measured using a double antibody sandwich ELISA. Also, serum total bilirubin (TB) and alanine aminotransferase (ALT) were measured by routine measures. RESULTS: The concentrations of serological markers of fibrosis in patients with active cirrhosis (ALC) were significantly higher than those in stationary liver cirrhosis (SLC) or NC groups. The levels of serological markers in HBeAg-positive patients were significantly higher than those in HBeAg-negative patients. In SLC and ALC patients, a negative linear correlation was found between IFN-gamma levels and the serological markers of fibrosis. IFN-gamma and IL-2 levels in the ALC group were significantly higher than those in the SLC and NC groups, but the statistical difference was not significant between the latter two. In contrast, IL-10 levels in the SLC group were significantly higher than that in the NC group, but no significant difference was found between SLC and ALC groups. The sIL-2R level was elevated gradually in all these groups, and the differences were significant. Positive linear correlations were seen between IFN-gamma activity and ALT levels (r = 0.339, P < 0.05), and IL-2 activity and TB levels (r = 0.517, P < 0.05). sIL-2R expression was positively correlated with both ALT and TB levels (r = 0.324, 0.455, P < 0.05), whereas there was no statistically significant correlation between IL-10 expression and serum ALT and TB levels (r = -0.102, -0.093, P > 0.05). Finally, there was a positive correlation between IFN-gamma and IL-2 levels. CONCLUSION: T cell immune responses are correlated with fibrosis and hepatic inflammatory activity and may play an important role in liver cirrhosis.