Evaluating the Oxygen Electrode Reactions of La Single-Atom Catalysts with the N/C Coordination Effect.

There is a growing demand for bifunctional electrocatalysts for oxygen electrodes in rechargeable metal-air batteries. This article investigates the bifunctional activity of La single-atom catalysts with N/C coordination (LaNxC6-x@Gra) using density functional theory (DFT). The augmentation of N coordination will result in enhanced synthetic stability. The coordination between nitrogen and carbon (N/C) has a significant influence on the working stability of the system under consideration. In the context of active atoms, the coordination between nitrogen and carbon (N/C coordination) has a significant impact on the electronic structure. This, in turn, influences the adsorption performance and catalytic activity of the catalysts. In the case of stable coordination environments, a correlation exists between the f-orbital center (εf) and the overpotential (η) via the adsorption free energy of intermediates (ΔG*ads). This correlation serves as a useful tool for predicting catalytic performance. The LaNxC6-x@Gra exhibits remarkable bifunctional activity due to its complementary performance, with an overpotential for the oxygen reduction reaction (ηORR) of 0.66 V and an overpotential for the oxygen evolution reaction (ηOER) of 0.43 V. This makes it a promising candidate for use as a bifunctional electrocatalyst in oxygen electrodes.

Determination of selpercatinib, a RET kinase inhibitor, in rat plasma and its application to a pharmacokinetic study.

Selpercatinib (LOXO-292) is a selective and potent RET inhibitor. A highly sensitive, rapid and specific high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for quantification of selpercatinib in rat plasma is reported. The method was validated in terms of selectivity, linearity, accuracy and precision, extraction recovery and matrix effect, stability and carryover as per the US Food and Drug Administration guidelines for bioanalytical method validation. Selpercatinib was detected by an electrospray ionization interface under selective reaction monitoring conditions in the positive ion mode. The calibration curve was linear over the concentration range from 1 to 2000 ng/ml with r2 = 0.9951. The intra- and inter-batch accuracy values ranged from 97.45 to 100.97% and from 98.70 to 100.74% with coefficients of variation of 2.45-6.99% and 5.89-7.99%, respectively. The extraction recovery and IS-normalized matrix factor were acceptable for the bioanalysis of selpercatinib. Additionally, selpercatinib was found to be stable under the detected conditions. It showed linear pharmacokinetic characteristics following oral administration to rats at 2.0-18.0 mg/kg. The results showed that the novel method for detecting selpercatinib in rat plasma could be successfully applied for quantification of selpercatinib in biosamples from nonclinical studies.

The effectiveness of teriflunomide in patients with multiple sclerosis in China: a real-world comparison to no DMT treatment in the first year after diagnosis.

Background: Teriflunomide is a first-line oral immunomodulatory agent approved in China for the treatment of relapsing multiple sclerosis. Objective: To compare the treatment outcomes of teriflunomide and no disease-modifying therapy (DMT) treatment (in first year) in multi-center real-world Chinese multiple sclerosis patients. Design: Retrospective study. Methods: This study was conducted in five tertiary hospitals in different geographical regions of China. We collected clinical data of patients treated with teriflunomide and no DMT treatment (in first year) between 1 January 2017 and 31 August 2021. The effectiveness of teriflunomide was described. Potential factors influencing the effectiveness of teriflunomide were investigated. Results: A total of 372 patients treated with teriflunomide and 148 no DMT treatment patients were included. A total of 292 patients were treated with teriflunomide for at least 6 months, described as a stable teriflunomide cohort. The annualized relapse rate was significantly lower in the stable teriflunomide cohort than in the no DMT treatment cohort (0.23 ± 0.47 versus 0.87 ± 0.67, p < 0.001). The mean Expanded Disability Status Scale (EDSS) score of the stable teriflunomide cohort (1.77 ± 1.62) was slightly different from that of the no DMT treatment cohort (2.09 ± 2.00). A previous annualized relapse rate of ⩾1, a previous EDSS score of ⩾2, and a long disease duration of ⩾5 years were associated with better clinical effectiveness. Conclusion: Teriflunomide is associated with a lower relapse rate and less disability accumulation in Chinese patients with multiple sclerosis.

Exosomes derived from human induced pluripotent stem cell-derived neural progenitor cells protect neuronal function under ischemic conditions.

Compared with other stem cells, human induced pluripotent stem cells-derived neural progenitor cells (iPSC-NPCs) are more similar to cortical neurons in morphology and immunohistochemistry. Thus, they have greater potential for promoting the survival and growth of neurons and alleviating the proliferation of astrocytes. Transplantation of stem cell exosomes and stem cells themselves have both been shown to effectively repair nerve injury. However, there is no study on the protective effects of exosomes derived from iPSC-NPCs on oxygen and glucose deprived neurons. In this study, we established an oxygen-glucose deprivation model in embryonic cortical neurons of the rat by culturing the neurons in an atmosphere of 95% N2 and 5% CO2 for 1 hour and then treated them with iPSC-NPC-derived exosomes for 30 minutes. Our results showed that iPSC-NPC-derived exosomes increased the survival of oxygen- and glucose-deprived neurons and the level of brain-derived neurotrophic factor in the culture medium. Additionally, it attenuated oxygen and glucose deprivation-induced changes in the expression of the PTEN/AKT signaling pathway as well as synaptic plasticity-related proteins in the neurons. Further, it increased the length of the longest neurite in the oxygen- and glucose-deprived neurons. These findings validate the hypothesis that exosomes from iPSC-NPCs exhibit a neuroprotective effect on oxygen- and glucose-deprived neurons by regulating the PTEN/AKT signaling pathway and neurite outgrowth. This study was approved by the Animal Ethics Committee of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China (approval No. SRRSH20191010) on October 10, 2019.

Gait characteristics and clinical relevance of hereditary spinocerebellar ataxia on deep learning.

BACKGROUND: Deep learning has always been at the forefront of scientific research. It has also been applied to medical research. Hereditary spinocerebellar ataxia (SCA) is characterized by gait abnormalities and is usually evaluated semi-quantitatively by scales. However, more detailed gait characteristics of SCA and related objective methods have not yet been established. Therefore, the purpose of this study was to evaluate the gait characteristics of SCA patients, as well as to analyze the correlation between gait parameters, clinical scales, and imaging on deep learning. METHODS: Twenty SCA patients diagnosed by genetic detection were included in the study. Ten patients who were tested via functional magnetic resonance imaging (fMRI) were included in the SCA imaging subgroup. All SCA patients were evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and Scale for the Assessment and Rating of Ataxia (SARA) clinical scales. The gait control group included 16 healthy subjects, and the imaging control group included seven healthy subjects. Gait data consisting of 10 m of free walking of each individual in the SCA group and the gait control group were detected by wearable gait-detection equipment. Stride length, stride time, velocity, supporting-phase percentage, and swinging-phase percentage were extracted as gait parameters. Cerebellar volume and the midsagittal cerebellar proportion in the posterior fossa (MRVD) were calculated according to MR. RESULTS: There were significant differences in stride length, velocity, supporting-phase percentage, and swinging-phase percentage between the SCA group and the gait control group. The stride length and stride velocity of SCA groups were lower while supporting phase was longer than those of the gait control group. SCA group's velocity was negatively correlated with both the ICARS and SARA scores. The cerebellar volume and MRVD of the SCA imaging subgroup were significantly smaller than those of the imaging control group. MRVD was significantly correlated with ICARS and SARA scores, as well as stride velocity variability. CONCLUSION: SCA gait parameters were characterized by a reduced stride length, slower walking velocity, and longer supporting phase. Additionally, a smaller cerebellar volume correlated with an increased irregularity in gait. Gait characteristics exhibited considerable clinical relevance to hereditary SCA. We conclude that a combination of gait parameters, ataxia scales, and MRVD may represent more objective markers for clinical evaluations of SCA.