A Fluorescent Switch Sensor for Glutathione Detection Based on Mn-doped CdTe Quantum Dots - Methyl Viologen Nanohybrids.

In the work, a fluorescence switch sensor consists of Mn-doped CdTe quantum dots (QDs) - methyl viologen (MV(2+)) nanohybrid is fabricated. In the sensor, MV(2+) plays a role in turning the QDs fluorescence to the "OFF" state due to the efficient electron transfer process while glutathione (GSH) could turn "ON" the native QDs fluorescence by effectively releasing QDs from the QDs-MV(2+) nanohybrids. In addition, the recovery level of QDs fluorescence is closely related to the amount of GSH. Based on this phenomenon, a reliable and convenient GSH quantitative determination method is established, which not only has a wide determination range of 1.2-200 µM, a low detection limit of 0.06 µM and a short detection time but also can realize the selective detection of GSH upon other competitive biothiols (homocysteine and cysteine) that are coexistent in biological systems. The developed sensor will greatly benefit to the study of GSH amount, helping the understanding of its function in biological systems.

A Simple Fluorescence Quenching Method for the Determination of Vanillin Using TGA-capped CdTe/ZnS Nanoparticles as Probes.

Based on the quenching of the fluorescence intensity of thioglycolic acid (TGA)-capped core-shell CdTe/ZnS nanoparticles (NPs) by vanillin, a novel, simple and rapid method for the determination of vanillin was proposed. In aqueous medium, the functionalized core-shell CdTe/ZnS NPs were successfully synthesized with TGA as the capping ligand. TGA-capped core-shell CdTe/ZnS NPs were characterized by using X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Factors affecting the vanillin detection were investigated, and the optimum conditions were also determined. Under the optimum conditions, the relative fluorescence intensity of CdTe/ZnS NPs was linearly proportional to vanillin over a concentration range from 9.4 × 10(-7) to 5.2 × 10(-4) M with a correlation coefficient of 0.998 and a detection limit of 2.6 × 10(-7) M. The proposed method was also employed to detect trace vanillin in cookies with satisfactory results.

[Study on whorl swarming growth phenomenon of Proteus mirabilis].

The present paper is aimed to explore the origins of Proteus mirabilis (PM) whorl swarming growth phenomenon. The whorl swarming growth phenomenon of PM was observed by changed bacterial culture inoculation time, humidity, vaccination practices, cultured flat placement, magnetic field, pH and other factors. Bacterial ring spiral direction of rotation is counterclockwise and the volatile growth process of PM was whorl swarming growth phenomenon. Spiro fluctuation phenomenon was of high frequency in the sealing tanks by cultured anytime inoculation, wherever inoculation technique applied or not, the presence or absence of the magnetic field, and wherever the dish position was. The experimental results showed that the whorl swarming growth phenomenon of PM requires specific pH environment, in which the facts may be relative to its genetic characteristics and the Earths rotation.

Exploration of adverse events associated with risdiplam use: Retrospective cases from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Risdiplam is a new drug for treating spinal muscular atrophy (SMA). However, pharmacovigilance analyses are necessary to objectively evaluate its safety-a crucial step in preventing severe adverse events (AEs). Accordingly, the primary objective of the current study was to examine the AEs associated with risdiplam use based on real-world data obtained from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. More specifically, we examined incidents reported between the third quarter of 2020 and the second quarter of 2023. The imbalance of risdiplam-related AEs was evaluated by computing the reporting odds ratio. A total of 5,406,334 reports were thoroughly reviewed. By removing duplicate reports, we identified 1588 reports in which risdiplam was the main suspected drug whose use was accompanied by 3470 associated AEs. Among the included AEs, 703 were categorized as serious and 885 as non-serious. Risdiplam use induced AEs across 18 organ systems, resulting in 130 positive signals. Notably, we detected new AE signals, including cardiac arrest, nephrolithiasis, tachycardia, loss of libido, and elevated hepatic enzyme activities; however, no ophthalmologic toxicity was reported. Although these new adverse reaction signals associated with risdiplam have been defined, long-term clinical studies are needed to confirm these findings. Nevertheless, our findings provide a valuable reference for improving the clinical management of SMA.

Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV) infection. Chemoradiotherapy is the mainstream treatment for locally advanced NPC, and chemotherapeutic drugs are an indispensable part of NPC treatment. However, the toxic side-effects of chemotherapy drugs limit their therapeutic value, and new chemotherapy drugs are urgently needed for NPC. Silvestrol, an emerging natural plant anticancer molecule, has shown promising antitumor activity in breast cancer, melanoma, liver cancer, and other tumor types by promoting apoptosis in cancer cells to a greater extent than in normal cells. However, the effects of silvestrol on NPC and its possible molecular mechanisms have yet to be fully explored. METHODS: Cell counting kit-8 (CCK-8), cell scratch, flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU), and Western blot (WB) assays were used to evaluate the effects of silvestrol on the cell viability, cell cycle, apoptosis, and migration of NPC cells. RNA sequencing (RNA-Seq) was used to study the effect of extracellular signal-regulated kinase (ERK) inhibitors on the cell transcriptome, and immunohistochemistry (IHC) to assess protein expression levels in patient specimens. RESULTS: Silvestrol inhibited cell migration and DNA replication of NPC cells, while promoting the expression of cleaved caspase-3, apoptosis, and cell cycle arrest. Furthermore, silvestrol altered the level of ERK phosphorylation. The ERK-targeted inhibitor LY3214996 attenuated silvestrol-mediated inhibition of NPC cell proliferation but not migration. Analysis of RNA-Seq data and WB were used to identify and validate the downstream regulatory targets of silvestrol. Expression of GADD45A, RAP1A, and hexokinase-II (HK2) proteins was inhibited by silvestrol and LY3214996. Finally, IHC revealed that GADD45A, RAP1A, and HK2 protein expression was more abundant in cancer tissues than in non-tumor tissues. CONCLUSIONS: Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.

The interaction effect between dopamine and task difficulty: Spontaneous eye blink rates diversely relate with Nogo-N2 across various task difficulties.

Nogo- N2 and P3 are the two major components in the neural time course of response inhibition (RI) and are both related, albeit differently, to dopamine (DA). However, contradictory results from previous studies imply that there may be an interaction effect between DA and task difficulty on the neural time course of RI. To investigate this, we assessed the correlation between spontaneous eye blink rate (EBR) and N2/P3 elicited by the Go/Nogo tasks across various task difficulties, manipulated by the Nogo-stimuli probability (NP) and Go-stimuli response deadline (RTD). In experiment 1, there were two conditions, low (20%) and high (40%) NP, both of which were fixed on an RTD of 1000 ms. We found that higher EBR was significantly related to a more negative Nogo-N2 amplitude. In experiment 2, there were also two conditions, long (1000 ms) and short (300 ms) RTD, both of which were fixed on an NP of 20%. We found that higher EBR was significantly related to more negative Nogo-N2 amplitude in both conditions, however, there was no significant correlation between EBR and P3 in both of the experiments. These results confirmed the interaction effect between DA and task difficulty on the neural course of the Go/Nogo task. This suggests that task difficulty should be considered in future studies that investigate the influence of DA on RI.

[Study on the sorption and isolation of shikimic acid by 717 anion exchange resin].

OBJECTIVE: To establish a convenient, practical and environmental method for extracting and isolating shikimic acid. METHODS: The content of shikimic acid was measured by RP-ion-pair HPLC, the effects of different pH, temperature, sample concentration and eluate concentration on 717 anion exchange resin were studied. RESULTS: The yield of shikimic acid was 96.52% on the condition of 22 degrees C, pH > 6.5, 7.5 mg /ml sample concentration and 0.03 mol/L HCl eluting. CONCLUSION: This method is feasible and suitable for the extraction and isolation of shikimic acid.