Zebrafish: A Pharmacological Model for Learning and Memory Research

Learning and memory are essential to organism survival and are conserved across various species, especially vertebrates. Cognitive studies involving learning and memory require using appropriate model organisms to translate relevant findings to humans. Zebrafish are becoming increasingly popular as one of the animal models for neurodegenerative diseases due to their low maintenance cost, prolific nature and amenability to genetic manipulation. More importantly, zebrafish exhibit a repertoire of neurobehaviors comparable to humans. In this review, we discuss the forms of learning and memory abilities in zebrafish and the tests used to evaluate the neurobehaviors in this species. In addition, the pharmacological studies that used zebrafish as models to screen for the effects of neuroprotective and neurotoxic compounds on cognitive performance will be summarized here. Lastly, we discuss the challenges and perspectives in establishing zebrafish as a robust model for cognitive research involving learning and memory. Zebrafish are becoming an indispensable model in learning and memory research for screening neuroprotective agents against cognitive impairment.     

Establishment and Application of a Predictive Growth Kinetic Model of Salmonella with the Appearance of Two Other Dominant Background Bacteria in Fresh Pork

To better guide microbial risk management and control, growth kinetic models of Salmonella with the coexistence of two other dominant background bacteria in pork were constructed. Sterilized pork cutlets were inoculated with a cocktail of Salmonella Derby (S. Derby), Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli), and incubated at various temperatures (4–37 °C). The predictive growth models were developed based on the observed growth data. By comparing R² of primary models, Baranyi models were preferred to fit the growth curves of S. Derby and P. aeruginosa, while the Huang model was preferred for E. coli (all R² ≥ 0.997). The secondary Ratkowsky square root model can well describe the relationship between temperature and μ_max (all R² ≥ 0.97) or Lag (all R² ≥ 0.98). Growth models were validated by the actual test values, with B_f and A_f close to 1, and MSE around 0.001. The time for S. Derby to reach a pathogenic dose (10⁵ CFU/g) at each temperature in pork was predicted accordingly and found to be earlier than the time when the pork began to be judged nearly fresh according to the sensory indicators. Therefore, the predictive microbiology model can be applied to more accurately predict the shelf life of pork to secure its quality and safety.     

Control Efficacy of Salicylic Acid Microcapsules against Postharvest Blue Mold in Apple Fruit

Salicylic acid (SA) is a natural inducer of disease resistance in fruit, but its application in the food industry is limited due to low water solubility. Here, SA was encapsulated in β-cyclodextrin (β-CD) via the host–guest inclusion complexation method, and the efficacy of SA microcapsules (SAM) against blue mold caused by Penicillium expansum in postharvest apple fruit was elucidated. It was observed that SAM was the most effective in inhibiting the mycelial growth of P. expansum in vitro. SAM was also superior to SA for control of blue mold under in vivo conditions. Enzyme activity analysis revealed that both SA and SAM enhanced the activities of superoxide dismutase (SOD) and phenylalanine ammonia lyase (PAL) in apple fruit, whereas SAM led to higher SOD activities than SA. Total phenolic contents in the SAM group were higher than those in the SA group at the early stage of storage. SAM also improved fruit quality by retarding firmness loss and maintaining higher total soluble solids (TSS) contents. These findings indicate that microcapsules can serve as a promising formulation to load SA for increasing P. expansum inhibition activity and improving quality attributes in apple fruit.     

Shikonin as a WT1 Inhibitor Promotes Promyeloid Leukemia Cell Differentiation

This study aims to observe the differentiating effect of shikonin on Wilms’ tumor 1 (WT1)-positive HL-60 cells and investigate the fate of the differentiated leukemia cells. WT1 overexpression unaffected cell viability but promoted resistance to H₂O₂-induced DNA injury and cell apoptosis. The binding of shikonin to the WT1 protein was confirmed by molecular docking and drug affinity reaction target stability (DARTS). Shikonin at the non-cytotoxic concentration could decrease the WT1 protein and simultaneously reduced the CD34 protein and increased the CD11b protein in a dose-dependent manner in normal HL-60 cells but not in WT1-overexpressed HL-60 cells. Shikonin unaffected HL-60 cell viability in 48 h. However, it lasted for 10 days; could attenuate cell proliferation, mitochondrial membrane potential (MMP), and self-renewal; prevent the cell cycle; promote cell apoptosis. In a mouse leukemia model, shikonin could decrease the WT1 protein to prevent leukemia development in a dose-dependent manner. In this study, we also confirmed preliminarily the protein–protein interactions between WT1 and CD34 in molecular docking and CO-IP assay. Our results suggest that: 1. shikonin can down-regulate the WT1 protein level for leukemia differentiation therapy, and 2. the interaction between WT1 and CD34 proteins may be responsible for granulocyte/monocyte immaturity in HL-60 cells.     

Epigallocatechin Gallate Attenuates Gentamicin-Induced Nephrotoxicity by Suppressing Apoptosis and Ferroptosis

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.     

O2 Carrier Myoglobin Also Exhibits β-Lactamase Activity That Is Regulated by the Heme Coordination State

Heme proteins perform a variety of biological functions and also play significant roles in the field of bio-catalysis. The β-lactamase activity of heme proteins has rarely been reported. Herein, we found, for the first time, that myoglobin (Mb), an O₂ carrier, also exhibits novel β-lactamase activity by catalyzing the hydrolysis of ampicillin. The catalytic proficiency ((k_cat/K_M)/k_uncat) was determined to be 6.25 × 10¹⁰, which is much higher than the proficiency reported for designed metalloenzymes, although it is lower than that of natural β-lactamases. Moreover, we found that this activity could be regulated by an engineered disulfide bond, such as Cys46-Cys61 in F46C/L61C Mb or by the addition of imidazole to directly coordinate to the heme center. These results indicate that the heme active site is responsible for the β-lactamase activity of Mb. Therefore, the study suggests the potential of heme proteins acting as β-lactamases, which broadens the diversity of their catalytic functions.     

Toward High-Energy-Density Aqueous Lithium-Ion Batteries Using Silver Nanowires as Current Collectors

The lack of suitable lightweight current collectors is one of the primary obstacles preventing the energy density of aqueous lithium-ion batteries (ALIBs) from becoming competitive. Using silver nanowire (AgNW) films as current collectors and a molecular crowding electrolyte, we herein report the fabrication of ALIBs with relatively good energy densities. In the 2 m LiTFSI–94% PEG–6% H₂O solution, the AgNW films with a sheet resistance of less than 1.0 ohm/square exhibited an electrochemical stability window as broad as 3.8 V. The LiMn₂O₄//Li₄Ti₅O₁₂ ALIBs using AgNW films as the current collectors demonstrated an initial energy density of 70 Wh/kg weighed by the total mass of the cathode and anode, which retained 89.1% after 50 cycles.     

Surface differences of oxide nanocrystals determined by geometry and exogenously coordinated water molecules

Determining the different surfaces of oxide nanocrystals is key in developing structure–property relations. In many cases, only surface geometry is considered while ignoring the influence of surroundings, such as ubiquitous water on the surface. Here we apply ¹⁷O solid-state NMR spectroscopy to explore the facet differences of morphology-controlled ceria nanocrystals considering both geometry and water adsorption. Tri-coordinated oxygen ions at the 1^st layer of ceria (111), (110), and (100) facets exhibit distinct ¹⁷O NMR shifts at dry surfaces while these ¹⁷O NMR parameters vary in the presence of water, indicating its non-negligible effects on the oxide surface. Thus, the interaction between water and oxide surfaces and its impact on the chemical environment should be considered in future studies, and solid-state NMR spectroscopy is a sensitive approach for obtaining such information. The work provides new insights into elucidating the surface chemistry of oxide nanomaterials.

Both atomic geometry and the influence of surroundings (e.g., exogenously coordinated water) are key issues for determining the chemical environment of oxide surfaces, whereas the latter is usually ignored and should be considered in future studies.     

Backbone-controlled LUMO energy induces intramolecular C–H activation in ortho-bis-9-borafluorene-substituted phenyl and o-carboranyl compounds leading to novel 9,10-diboraanthracene derivatives

The choice of backbone linker for two ortho-bis-(9-borafluorene)s has a great influence on the LUMO located at the boron centers and, therefore, the reactivity of the respective compounds. Herein, we report the room temperature rearrangement of 1,2-bis-(9-borafluorenyl)-ortho-carborane, C₂B₁₀H₁₀-1,2-[B(C₁₂H₈)]₂ ([2a]) featuring o-carborane as the inorganic three-dimensional backbone and the synthesis of 1,2-bis-(9-borafluorenyl)benzene, C₆H₄-1,2-[B(C₁₂H₈)]₂ (2b), its phenylene analog. DFT calculations on the transition state for the rearrangement support an intramolecular C–H bond activation process via an S_EAr-like mechanism in [2a], and predicted that the same rearrangement would take place in 2b, but at elevated temperatures, which indeed proved to be the case. The rearrangement gives access to 3a and 3b as dibora-benzo[a]fluoroanthene isomers, a form of diboron polycyclic aromatic hydrocarbon (PAH) that had yet to be explored. The isolated compounds 2b, 3a, and 3b were fully characterized by NMR, HRMS, cyclic voltammetry (CV), single-crystal X-ray diffraction analysis, and photophysical measurements, supported by DFT and TD-DFT calculations.

The backbone linker for two ortho-bis-(9-borafluorene)s influences the LUMO at the boron centers and the reactivity of the respective compounds.