Neurodevelopmental toxicity of pyrazinamide to larval zebrafish and the restoration after intoxication withdrawal.

To investigate the neurotoxicity of pyrazinamide (PZA) to larval zebrafish, the PZA effects were assessed followed by its mechanism being explored. Same as isoniazid (INH), this compound is a first-line anti-tuberculosis drug and is suggested to be a risk that inducing nerve injury with long-term intoxication. Our findings indicated that zebrafish larvae obtained severe nerve damage secondary to constant immersion in various concentrations of PZA (i.e., 0.5, 1.0, and 1.5 mM) from 4 hpf (hours post fertilization) onwards until 120 hpf. The damage presented as dramatically decrease of locomotor capacity and dopaminergic neuron (DAN)-rich region length in addition to defect of brain blood vessels (BBVs). Moreover, PZA-administrated zebrafish showed a decreased dopamine (DA) level and downregulated expression of neurodevelopment-related genes, such as shha, mbp, neurog1, and gfap. However, secondary to 48-h restoration in fish medium (i.e., at 168 hpf), the neurotoxicity described above was prominently ameliorated. The results showed that PZA at the concentrations we tested was notably neurotoxic to larval zebrafish, and this nerve injury was restorable after PZA withdrawing. Therefore, this finding will probably provide a reference for clinical medication.

Mixing Performance Analysis and Optimal Design of a Novel Passive Baffle Micromixer.

Micromixers, as crucial components of microfluidic devices, find widespread applications in the field of biochemistry. Due to the laminar flow in microchannels, mixing is challenging, and it significantly impacts the efficiency of rapid reactions. In this study, numerical simulations of four baffle micromixer structures were carried out at different Reynolds numbers (Re = 0.1, Re = 1, Re = 10, and Re = 100) in order to investigate the flow characteristics and mixing mechanism under different structures and optimize the micromixer by varying the vertical displacement of the baffle, the rotation angle, the horizontal spacing, and the number of baffle, and by taking into account the mixing intensity and pressure drop. The results indicated that the optimal mixing efficiency was achieved when the baffle's vertical displacement was 90 µm, the baffle angle was 60°, the horizontal spacing was 130 µm, and there were 20 sets of baffles. At Re = 0.1, the mixing efficiency reached 99.4%, and, as Re increased, the mixing efficiency showed a trend of, first, decreasing and then increasing. At Re = 100, the mixing efficiency was 97.2%. Through simulation analysis of the mixing process, the structure of the baffle-type micromixer was effectively improved, contributing to enhanced fluid mixing efficiency and reaction speed.

Broadband hyperbolic thermal metasurfaces based on the plasmonic phase-change material In3SbTe2.

Thermal radiation modulation facilitated by phase change materials (PCMs) needs a large thermal radiation contrast in broadband as well as in a non-volatile phase transition, which are only partially satisfied by conventional PCMs. In contrast, the emerging plasmonic PCM In3SbTe2 (IST) that undergoes a non-volatile dielectric-to-metal phase transition during crystallization offers a fitting solution. Here, we have prepared IST-based hyperbolic thermal metasurfaces and demonstrated their capabilities to modulate thermal radiation. By laser-printing crystalline IST gratings with different fill factors on amorphous IST films, we have achieved multilevel, large-range, and polarization-dependent control of the emissivity modulation (0.07 for the crystalline phase and 0.73 for the amorphous phase) over a broad bandwidth (8-14 µm). With the convenient direct laser writing technique that supports large-scale surface patterning, we have also demonstrated promising applications of thermal anti-counterfeiting with hyperbolic thermal metasurfaces.

Radix Panacis quinquefolii Extract Ameliorates Inflammatory Bowel Disease through Inhibiting Inflammation.

OBJECTIVE: To investigate the anti-inflammatory activity of Radix Panacis quinguefolii root extract (RPQE) and its therapeutic effects on inflammatory bowel disease (IBD). METHODS: The 72-hour post-fertilization zebrafish was used to generate the local and systematic inflammation models through tail-amputation and lipopolysaccharide (LPS)-induction (100 µ g/mL), respectively. The Tg(zlyz:EGFP) zebrafish was induced with 75 µ g/mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) for establishing the IBD model. The tail-amputated, LPS-, and TNBS-induced models were subjected to RPQE (ethanol fraction, 10-20 µ g/mL) administration for 12 and 24 h, respectively. Anti-inflammatory activity of RPQE was evaluated by detecting migration and aggregation of leukocytes and expression of inflammation-related genes. Meanwhile, TNBS-induced fish were immersed in 0.2% (W/V) calcein for 1.5 h and RPQE for 12 h before photographing to analyze the intestinal efflux efficiency (IEE). Moreover, the expression of inflammation-related genes in these fish was detected by quantitative polymerase chain reaction. RESULTS: Subject to RPQE administration, the migration and aggregation of leukocytes were significantly alleviated in 3 zebrafish models (P<0.01). Herein, RPQE ameliorated TNBS-induced IBD with respect to a significantly reduced number of leukocytes, improved IEE, and inhibited gene expression of pro-inflammatory factors (P<0.05 or P<0.01). CONCLUSION: RPQE exhibited therapeutic effects on IBD by inhibiting inflammation.

Involvement of dopamine signaling pathway in neurodevelopmental toxicity induced by isoniazid in zebrafish.

AIMS: This study evaluated the neurodevelopmental toxicity of isoniazid (INH) in zebrafish embryos and the underlying mechanism. METHODS: Zebrafish embryos were exposed to different concentrations (2 mM, 4 mM, 8 mM, 16 mM, 32 mM) INH for 120 hpf. During the exposure period, the percentage of embryo/larva mortality, hatching, and morphological malformation were checked every 24 h until 120 hpf. The development of blood vessels in the brain was observed at 72 hpf and 120 hpf, and behavioral capacity and acridine orange (AO) staining were measured at 120 hpf. Alterations in the mRNA expression of apoptosis and dopamine signaling pathway related genes were assessed by real-time quantitative PCR (qPCR). RESULTS: INH considerably inhibited zebrafish embryo hatching and caused zebrafish larval malformation (such as brain malformation, delayed yolk sac absorption, spinal curvature, pericardial edema, and swim bladder defects). High concentration of INH (16 mM, 32 mM) even induced death of zebrafish. In addition, INH exposure markedly restrained the ability of the zebrafish autonomous movement, shortened the length of dopamine neurons and inhibited vascular development in the brain. No obvious apoptotic cells were observed in the control group, whereas considerable numbers of apoptotic cells appeared in the head of INH-treated larvae at 120 hpf. PCR results indicated that INH significantly raised the transcription levels of caspase-3, -8, -9, and bax and significantly decreased bcl-2 and bcl-2/bax in the zebrafish apoptotic signaling pathway. INH also markedly decreased the genes related to dopamine signaling pathway (th1, dat, drd1, drd2a, drd3, and drd4b). CONCLUSIONS: Experimental results indicated that INH had obvious neurodevelopmental toxicity in zebrafish. Persistent exposure to INH for 120 h caused apoptosis, decreased dopaminergic gene expression, altered vasculature, and reduced behaviors.