Generation of induced pluripotent stem cells (ZZUCSBi001-A) from skin fibroblasts of a healthy donor.

Fibroblasts were extracted from the scalp of a healthy 55-year-old male and subsequently transformed into pluripotent stem cells by introducing episomal plasmids harboring essential reprogramming factors. These induced pluripotent stem cells exhibited a normal karyotype and demonstrated the capacity to differentiate into all three germ layers, as confirmed through teratoma assays. This specific cell line serves as a valuable reference for comparative investigations alongside other induced pluripotent stem cell lines generated from somatic cells of patients afflicted by genetic neurodegenerative disorders.

Bidirectional associations between maladaptive cognitions and emotional symptoms, and their mediating role on the quality of life in adults with ADHD: a mediation model.

Background/objectives: Adults with attention-deficit/hyperactivity disorder (ADHD) have more maladaptive cognitions, emotional problems and a poorer quality of life (QoL). A verification of the psychological model in clinical samples is needed for a better understanding of the mechanisms of ADHD diagnosis on QoL via maladaptive cognitions, emotional symptoms, and their interactions. Methods: 299 ADHD participants and 122 healthy controls were recruited. ADHD core symptoms, maladaptive cognitions, emotional symptoms and psychological QoL were rated. Pearson's correlation and structural equation modeling were analyzed to explore the relationship and influence of ADHD diagnosis on QoL. Results: More maladaptive cognitions, emotional symptoms, and poorer QoL were found in the ADHD group, and the dysfunctional attitudes were on par between ADHD with or without medication (p = 0.368). Moderate to strong correlations were found between emotional symptoms, maladaptive cognitions and QoL, and ADHD core symptoms presented correlations among the above scores (r = 0.157 ~ 0.416, p < 0.01) in ADHD participants. The influence of ADHD diagnosis on QoL was mediated through maladaptive cognitions, emotional symptoms, and their bidirectional interactions (p < 0.05), especially those with stable medication. Conclusion: Our study is the first to verify the psychological model in adults with ADHD in China. The findings determined the direct influence of ADHD diagnosis on QoL and the indirect influence through maladaptive cognitions, emotional symptoms, and their interactions, emphasizing the importance of interventions for emotional symptoms and maladaptive cognitions for ADHD patients both with or without medication for a better QoL outcome.

Progress in pH-Sensitive sensors: essential tools for organelle pH detection, spotlighting mitochondrion and diverse applications.

pH-sensitive fluorescent proteins have revolutionized the field of cellular imaging and physiology, offering insight into the dynamic pH changes that underlie fundamental cellular processes. This comprehensive review explores the diverse applications and recent advances in the use of pH-sensitive fluorescent proteins. These remarkable tools enable researchers to visualize and monitor pH variations within subcellular compartments, especially mitochondria, shedding light on organelle-specific pH regulation. They play pivotal roles in visualizing exocytosis and endocytosis events in synaptic transmission, monitoring cell death and apoptosis, and understanding drug effects and disease progression. Recent advancements have led to improved photostability, pH specificity, and subcellular targeting, enhancing their utility. Techniques for multiplexed imaging, three-dimensional visualization, and super-resolution microscopy are expanding the horizon of pH-sensitive protein applications. The future holds promise for their integration into optogenetics and drug discovery. With their ever-evolving capabilities, pH-sensitive fluorescent proteins remain indispensable tools for unravelling cellular dynamics and driving breakthroughs in biological research. This review serves as a comprehensive resource for researchers seeking to harness the potential of pH-sensitive fluorescent proteins.

UPLC-MS/MS for the Simultaneous Determination of Sildenafil and N-Desmethyl Sildenafil.

A sensitive high-performance liquid chromatography-tandem mass spectrometry method was established for the simultaneous determination of sildenafil and N-desmethyl sildenafil in human plasma. The protein precipitation was used for extraction and the gradient elution of the mobile phase A of water (containing 0.01% formic acid) and the mobile phase B of acetonitrile, and methanol (V:V = 1:1, containing 0.01% formic acid) was used for chromatographic separation on a C18 column. Quantification was performed by multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 475.4 â†’ m/z 283.3 for sildenafil, m/z 461.4 â†’ m/z 283.2 for N-desmethyl sildenafil, m/z 483.3 â†’ m/z 108.1 for sildenafil-d8 (IS) and m/z 469.2 â†’ m/z 283.3 for N-desmethyl sildenafil-d8 (IS) at the positive ionization mode. The intra- and inter-day relative standard deviations were less than 6.8% and 4.1% for sildenafil and N-desmethyl sildenafil, respectively. Accuracy at four levels ranged from 93.1% to 115.9% for sildenafil and 95.6% to 112.5% for N-desmethyl sildenafil. The present method was sensitive and reliable for simultaneous quantification of sildenafil and its active metabolite and was successfully applied to a pharmacokinetic study of an oral low dose of sildenafil in Chinese healthy volunteers.

An improved LC-MS/MS method for determination of cinacalcet in human plasma and its application to the evaluation of food intake effect on the pharmacokinetics of cinacalcet in healthy volunteers.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of cinacalcet in human plasma was developed and validated. This assay was based on liquid-liquid extraction and cinacalcet-d4 was used as an internal standard (IS). Separation was achieved on a C18 column by the mobile phase A of water (containing 0.1% formic acid) and the mobile phase B of acetonitrile-water (95:5, v/v) (containing 0.2% formic acid) with gradient elution. Quantification was done using multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 358.2 → m/z 155.2 for cinacalcet and m/z 362.3 → m/z 155.0 for IS at positive ionization mode. The calibration curve was established over the range 0.05-20.0 ng/mL and the correlation coefficient was >0.99. The intra- and inter-day relative standard deviations were <5.8%. Accuracy determined at four concentrations ranged between 96.0 and 106.0%. This method was successfully applied to a pharmacokinetic description of oral dose of cinacalcet and the significant effect of food intake on the pharmacokinetics of cinacalcet was first demonstrated in Chinese healthy volunteers.