Highly sensitive electrochemical quantification of carbendazim via synergistic enhancement of ring-opening metathesis polymerization and polyethyleneimine modified graphene oxide.

A novel aptamer-based sensor was developed using the signal amplification strategy of ring-opening metathesis polymerization (ROMP) and polyethyleneimine modified graphene oxide to achieve trace detection of carbendazim (CBZ). The dual identification of aptamer and antibody was used to avoid false positive results and improve the selectivity. Polyethyleneimine modified graphene oxide (GO-PEI), as a substrate material with excellent conductivity, was modified on the surface of a glassy carbon electrode (GCE) to increase the grafting amount of aptamer on the electrode surface. Moreover, a large number of cyclopentenyl ferrocene (CFc) was aggregated to form long polymer chains through ring-opening metathesis polymerization (ROMP), so as to significantly improve the detection sensitivity of the biosensor. The linear range of this sensor was 1 pg/mL-100 ng/mL with a detection limit as low as 7.80 fg/mL. The sensor exhibited excellent reproducibility and stability, and also achieved satisfactory results in actual sample detection. The design principle of such a sensor could provide innovative ideas for sensors in the detection of other types of targets.

A controllable Y-shaped DNA structure assisted aptasensor for the simultaneous detection of AFB1 and OTA based on ARGET ATRP.

The development of a simple, rapid, and sensitive technology for the simultaneous detection of mycotoxins is of great significance in ensuring the safety of foods and drugs. Herein, a fluorescence aptasensor with high sensitivity and reproducibility for the simultaneous detection of aflatoxin B1 (AFB1) and ochratoxin A (OTA) was developed. In this sensing system, AFB1 and OTA aptamers were co-immobilized on the surface of magnetic beads (MBs) to form a Y-shaped structure through the principle of complementary base pairing, and were used as recognition probes to specifically capture the target. Activators regenerated by electron transfer for atom transfer radical polymerization (ARGET ATRP) was used as a signal amplification strategy to improve the sensitivity. The initiator modified at the end of an antibody initiates the ARGET ATRP reaction. Different fluorescence signals were designed to achieve the simultaneous detection of OTA and AFB1 with limits of 426.18 and 79.55 fg mL-1 for AFB1 and OTA, respectively. In addition, experiments were conducted on three types of samples, and the recoveries of the two mycotoxins ranged from 87.30% to 109.50%, with relative standard deviations ranging from 0.50% to 4.92% under reproducible conditions. The results suggest that the developed aptasensor is sufficient to meet the different regulatory requirements of the two mycotoxins in food and drug safety and shows great potential.

Sex-dependent difference in the relationship between thyroid hormones and gallstone disease in euthyroid subjects.

The relationship between thyroid dysfunction and gallstone disease (GSD) has been examined by some observational studies. However, evidence about the relationship between thyroid function and GSD among euthyroid subjects was scarce. The aim of this study was to investigate the association between thyroid function and the presence of GSD in a large-sample euthyroid subjects. A total of 5476 euthyroid subjects who underwent health checkup were included. GSD was diagnosed by hepatic ultrasonography. Conventional risk factors for GSD were assessed as well as serum levels of TSH, TT3, TT4 and Log-transformed TT3/TT4 ratio. A total of 4958 subjects were finally included. Levels of TSH, TT3, TT4, and ln (TT3/TT4) were comparable between GSD and non-GSD group (TSH: 1.73 ±â€…1.07 vs 1.74 ±â€…1.07 mIU/L, P = .931; TT3: 1.55 ±â€…0.40 vs 1.54 ±â€…0.39 ng/mL, P = .797; TT4: 9.37 ±â€…2.07 vs 9.49 ±â€…2.06 ug/dL, P = .245, ln (TT3/TT4): -1.80 ±â€…0.23 vs -1.83 ±â€…0.23, P = .130, respectively). Multivariate logistic regression analysis among all subjects revealed that the thyroid function parameters did not reach significant difference. Subgroup analyses showed that the relationship between thyroid function and GSD was different according to gender, with negative association for ln (TT3/TT4) and (odds ratio:0.551, 95% CI: 0.306-0.992, P = .047) and positive association for TT4 (odds ratio:1.077, 1 95% CI: .001-1.158, P = .046) in men. None of the thyroid function parameters was significantly associated with GSD in women. Our findings indicated that low levels of TT3-to-TT4 ratio and high levels of TT4 were significantly and independently associated with GSD among euthyroid male subjects, but not female subjects.

RFTN1 facilitates gastric cancer progression by modulating AKT/p38 signaling pathways.

Gastric cancer (GC), a malignant tumor originating from the epithelium of the gastric mucosa, has been endangering human health for many years. The current standard surgical resection is not ideal for advanced gastric cancer. Therefore, it is urgent to find new prognostic indicators as well as drug targets. In our study, referring to clinicopathological characteristics of GC, we found that raftlin lipid raft linker 1 (RFTN1) had high expression in primary GC tissues. Subsequently, we showed that knockdown of RFTN1 inhibited GC cell proliferation and induced cell cycle arrest in G0/G1 phase, and promoted GC cell apoptosis. Conversely, overexpression of RFTN1 promoted GC cell proliferation and G0/G1 to S phase transition, and inhibited apoptosis. Furthermore, cell derived xenograft experiments showed that knockdown of RFTN1 inhibited GC cell growth in vivo. Notably, our experimental data demonstrated that knockdown of RFTN1 could inhibit the AKT signaling pathway and activate p38 signaling pathway, whereas overexpression of RFTN1 did the opposite. Moreover, the effects caused by knockdown of RFTN1 in GC cells could be rescued by using SC79 (an AKT activator). In conclusion, these results indicated that RFTN1 plays an oncogenic role in GC, and might act as a prospective prognostic indicator or therapeutic target for GC patients.

Control of Laves Precipitation in a FeCrAl-based Alloy Through Severe Thermomechanical Processing.

In recent years, the development of nuclear grade FeCrAl-based alloys with enhanced accident tolerance has been carried out for light water reactor (LWR) fuel cladding to serve as a substitute for zirconium-based alloys. To achieve excellent microstructure stability and mechanical properties, the control of precipitation particles is critical for application of FeCrAl-based alloys. In this paper, the effect of thermomechanical processing on the microstructure and precipitation behavior of hot-rolled FeCrAl alloy plates was examined. After hot rolling, the FeCrAl alloy plates had typical deformation textures. The rolling direction (RD) orientation gradually rotated from <100> to <110> along with increasing reduction. Shear bands and cell structures were formed in the matrix, and the former acted as preferable nucleation sites for crystallization. Improved deformation helped to produce strain-induced precipitation. The plate with 83% reduction had the most homogeneous and finest precipitation particles. Identification results by TEM indicated that the Laves precipitation was of the Fe2Nb-type crystal structure type, with impurities including Mo, Cr, and Si. The plate with uniform Laves particles displayed favorable heat stability after a long period of aging at 800 °C. The microstructure evolution of the aged sample was also observed. The deformation microstructure and the strain-induced precipitation mechanism of FeCrAl alloys are discussed.

Influence of grapefruit juice on pharmacokinetics of triptolide in rats grapefruit juice on the effects of triptolide.

1. Triptolide, a major pharmacological component isolated from Tripterygium wilfordii Hook F (TWHF), is a substrate of both CYP3A4 and P-glycoprotein (P-gp). 2. This study investigates the effects of GFJ on the pharmacokinetics of triptolide in rats. 3. The pharmacokinetics of orally administered triptolide with or without GFJ pretreatment were investigated. A mechanistic study was also undertaken using the Caco-2 cell transwell model and rat liver microsomes incubation systems to support the in vivo pharmacokinetic data. 4. The results indicated that coadministration of GFJ could increase the systemic exposure of triptolide significantly, including area under the curve (828.58 ± 79.72 versus 541.53 ± 45.23 ng·h/mL) and maximum plasma concentration (273.58 ± 27.98 versus 193.67 ± 10.08 ng/mL). The apparent permeability of triptolide across the Caco-2 cell transwell model increased significantly with the pretreatment of GFJ (from 1.62 ± 0.25 × 10-6 to 2.51 ± 0.41 × 10-6 cm/s), and the metabolic stability of triptolide was also increased from 32.6 ± 5.1 to 52.5 ± 7.8 min with the pretreatment of GFJ, and the difference was significant (p < 0.05). 5. In conclusion, GFJ could increase the systemic exposure of triptolide in rats, when GFJ and triptolide was coadministered, and it might work mainly through increasing the absorption of triptolide by inhibiting P-gp, or through slowing down the metabolism of triptolide in rat liver by inhibiting the activity of CYP3A4.

Effects of type 2 diabetes mellitus on the pharmacokinetics of berberine in rats.

CONTEXT: Berberine is an active alkaloid isolated from Rhizoma coptidis [Coptis chinensis Franch. (Ranunculaceae)] that is widely used for the treatment of diabetes, hyperlipidemia and hypertension. However, the pharmacokinetics of berberine in normal rats and type 2 diabetes mellitus (T2DM) model rats are not clear. OBJECTIVE: This study compares the pharmacokinetics of berberine between normal and T2DM model rats. MATERIALS AND METHODS: The T2DM model rats were fed with high fat diet for 4 weeks, induced by low-dose (30 mg/kg) streptozotocin for 72 h and validated by determining the peripheral blood glucose level. Rats were orally treated with berberine at a dose of 20 mg/kg and then berberine concentration in rat plasma was determined by employing a sensitive and rapid LC-MS/MS method. RESULTS: The significantly different pharmacokinetic behaviour of berberine was observed between normal and T2DM model rats. When compared with the normal group, Cmax, t1/2 and AUC(0-t) of berberine were significantly increased in the model group (17.35 ± 3.24 vs 34.41 ± 4.25 µg/L; 3.95 ± 1.27 vs 9.29 ± 2.75 h; 151.21 ± 23.96 vs 283.81 ± 53.92 µg/h/L, respectively). In addition, oral clearance of berberine was significantly decreased in the model group (134.73 ± 32.15 vs 62.55 ± 16.34 L/h/kg). DISCUSSION AND CONCLUSION: In T2DM model rats, the pharmacokinetic behaviour of berberine was significantly altered, which indicated that berberine dosage should be modified in T2DM patients.