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Background: Although observational studies indicated connections between fatty acids (FAs) and Alzheimer's disease and dementia, uncertainty persists regarding how these relationships extend to dementia with Lewy bodies (DLB). Objective: To explore the potential causal relationships between FAs and the development of DLB, thus clarifying these associations using genetic instruments to infer causality. Methods: We applied a two-sample Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) approach. Genetic data were obtained from a DLB cohort, comprising 2,591 cases and 4,027 controls of European descent. Eight FAs, including linoleic acid, docosahexaenoic acid, monounsaturated fatty acid, omega-3 fatty acid, omega-6 fatty acid, polyunsaturated fatty acid, saturated fatty acid, and total fatty acid, were procured from a comprehensive GWAS of metabolic biomarkers of UK Biobank, conducted by Nightingale Health in 2020 (met-d), involving 114,999 individuals. Our analysis included inverse-variance weighted, MR-Egger, weighted-median, simple mode, and weighted-mode MR estimates. Cochran's Q-statistics, MR-PRESSO, and MR-Egger intercept test were used to quantify the heterogeneity and horizontal pleiotropy of instrumental variables. Results: Only linoleic acid showed a significant genetic association with the risk of developing DLB in the univariate MR. The odds ratio for linoleic acid was 1.337 with a 95% confidence interval of 1.019–1.756 (pIVW = 0.036). Results from the MVMR showed that no FAs were associated with the incidence of DLB. Conclusions: The results did not support the hypothesis that FAs could reduce the risk of developing DLB. However, elucidating the relationship between FAs and DLB risk holds potential implications for informing dietary recommendations and therapeutic approaches in DLB. [ABSTRACT FROM AUTHOR]

Zebra finch song behavior is sexually dimorphic: males sing and females do not. The neuralsystem underlying this behavior is sexually dimorphic, and this sex difference is easy to quantify.During development, the zebra finch song system can be altered by steroid hormones,specifically estradiol, which actually masculinizes it. Because of the ease of quantification andexperimental manipulation, the zebra finch song system has great potential for use inundergraduate labs.Unfortunately, the underlying costs prohibit use of this system in undergraduate labs. Further, thetime required to perform a developmental study renders such undertakings unrealistic within asingle academic term.We have overcome these barriers by creating digital tools, including an image library of songnuclei from zebra finch brains. Students using this library replicate and extend a publishedexperiment examining the dose of estradiol required to masculinize the female zebra finch brain.We have used this library for several terms, and students not only obtain significant experimentalresults but also make gains in understanding content, experimental controls, and inferentialstatistics (ANOVA and post-hoc tests). We have provided free access to these digital tools athttp://mdcune.psych.ucla.edu/modules/birdsong.

Zebra finch song behavior is sexually dimorphic: males sing and females do not. The neural system underlying this behavior is sexually dimorphic, and this sex difference is easy to quantify. During development, the zebra finch song system can be altered by steroid hormones, specifically estradiol, which actually masculinizes it. Because of the ease of quantification and experimental manipulation, the zebra finch song system has great potential for use in undergraduate labs. Unfortunately, the underlying costs prohibit use of this system in undergraduate labs. Further, the time required to perform a developmental study renders such undertakings unrealistic within a single academic term. We have overcome these barriers by creating digital tools, including an image library of song nuclei from zebra finch brains. Students using this library replicate and extend a published experiment examining the dose of estradiol required to masculinize the female zebra finch brain. We have used this library for several terms, and students not only obtain significant experimental results but also make gains in understanding content, experimental controls, and inferential statistics (analysis of variance and post hoc tests). We have provided free access to these digital tools at the following website: http://mdcune.psych.ucla.edu/modules/birdsong. (Contains 6 figures and 1 table.)

Pulmonary aspergillosis, which is a secondary complication of fungal pneumonia, is widely considered to have an increasing incidence and high mortality. Itraconazole (Itz) can inhibit ergosterol biosynthesis to treat pulmonary aspergillosis. Nevereless, Itz's clinical application is limited because of its poor water solubility, low oral bioavailability, and systemic hepatotoxicity. In this study, Itz-loaded nanostructured lipid carriers (Itz-NLCs) were developed to improve the in vitro permeability and bioavailability of Itz via pulmonary administration. Itz-NLCs were prepared by the emulsification-evaporation method using oleic acid and glycerol monostearate as liquid and solid lipids, respectively. The Itz-NLCs were optimized with tiny particle size, uniform distribution, and excellent entrapment efficiency (EE, 97.57% ± 0.45%). A Xenopus alveolar membrane was used in the permeation study, and the cumulative permeation percentage of Itz was 10% for Itz-NLCs at 8 h, which was 2.50-fold higher than that for Itz suspensions (4%, p <.001). A rabbit pharmacokinetic investigation revealed that Itz-NLCs have an 83.05% absolute bioavailability after intratracheal instillation. The purpose of Itz-NLCs is to enhance the bioavailability and permeability of Itz in vitro for administration via the lungs. [ABSTRACT FROM AUTHOR]

Unecritinib (TQ-B3101) is a selective tyrosine kinase receptor inhibitor. In the study, in vitro metabolic experiments revealed that the hydrolysis of TQ-B3101 was mainly catalyzed by carboxylesterase 2 (CES2), followed by CES1. Next, a sensitive and reliable LC-MS/MS method was established for the simultaneous determination of TQ-B3101 and its metabolite crizotinib in rat plasma. To prevent in vitro hydrolysis of TQ-B3101, sodium fluoride, the CESs inhibitor at a concentration of 2 M , was immediately added after whole blood collection. Plasma samples were extracted by acetonitrile-induced protein precipitation method, and chromatographically separated on a Gemini C 18 column (50 mm × 2.0 mm i.d., 5 μm) using gradient elution with a mobile phase of 0.1% formic acid and 5 mmol/L ammonium acetate with 0.1% formic acid. The retention times for TQ-B3101 and crizotinib were 2.61 and 2.38 min, respectively. The analytes were detected with tandem mass spectrometer by positive electrospray ionization, using the ion transitions at m/z 492.3 → 302.3 for TQ-B3101, m/z 450.3 → 260.3 for crizotinib, and m/z 494.0 → 394.3 for imatinib (internal standard). Method validation was conducted in the linear range of 1.00–800 ng/mL for the two analytes. The precision, accuracy and stabilities all met the acceptance criteria. The pharmacokinetic study indicated that TQ-B3101 was rapidly hydrolyzed to crizotinib with the elimination half-life of 1.11 h after a single gavage administration of 27 mg/kg to Sprague-Dawley rats, and the plasma exposure of TQ-B3101 was only 2.98% of that of crizotinib. • TQ-B3101 is an amide prodrug of crizotinib, a selective tyrosine kinase receptor inhibitor. • First LC-MS/MS method for the simultaneous quantification of TQ-B3101 and crizotinib in rat plasma. • The developed method was successfully applied to a pharmacokinetic study. [ABSTRACT FROM AUTHOR]

Parkinson's disease confronts challenges in drug delivery due to the blood-brain barrier. Intranasal delivery bypasses the blood-brain barrier for improved drug bioavailability, yet narrow nasal space and brief retention time hinder clinical applicability. We conducted a Bromocriptine Mesylate-loaded PLGA nanoparticles co-modified with low molecular weight protamine (LMWP) and lactoferrin (Lf) (LMWP/Lf-BCM-NPs) for nose-to-brain delivery. The resulting LMWP/Lf-BCM-NPs were uniform spheres with an average size of 248.53 ± 16.25 nm and zeta potential of -2.63 ± 0.74 mV. Fourier transform infrared spectroscopy confirmed LMWP and Lf attachment. The co-modified nanoparticles showed improving cellular transport and good viability. The LMWP/Lf-BCM-NPs showed increased brain targeting efficiency in mice. In haloperidol-induced Parkinson mouse models, the LMWP/Lf-BCM-NPs showed increased brain targeting efficiency, enhanced behavioral regulatory effects, enhanced antioxidant effects and neuroprotection effects. This study paves the way for a novel, non-invasive brain-targeted therapy, offering a promising avenue for Parkinson's disease clinical treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Since the emergence of SARS-CoV-2 viruses, multiple mutant strains have been identified. Infection with SARS-CoV-2 virus leads to alterations in host cell phosphorylation signal, which systematically modulates the immune response., Methods: Identification and analysis of SARS-CoV-2 virus infection phosphorylation sites enable insight into the mechanisms of viral infection and effects on host cells, providing important fundamental data for the study and development of potent drugs for the treatment of immune inflammatory diseases. In this paper, we have analyzed the SARS-CoV-2 virus-infected phosphorylation region and developed a transformer-based deep learning-assisted identification method for the specific identification of phosphorylation sites in SARS-CoV-2 virus-infected host cells., Results: Furthermore, through association analysis with lung cancer, we found that SARS-CoV-2 infection may affect the regulatory role of the immune system, leading to an abnormal increase or decrease in the immune inflammatory response, which may be associated with the development and progression of cancer., Conclusion: We anticipate that this study will provide an important reference for SARS-CoV-2 virus evolution as well as immune-related studies and provide a reliable complementary screening tool for anti-SARS-CoV-2 virus drug and vaccine design., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)