Histone lactylation-ROS loop contributes to light exposure-exacerbated neutrophil recruitment in zebrafish.

Light serves as a crucial external zeitgeber for maintaining and restoring physiological homeostasis in most organisms. Disrupting of light rhythms often leads to abnormal immune function, characterized by excessive inflammatory responses. However, the underlying regulatory mechanisms behind this phenomenon remain unclear. To address this concern, we use in vivo imaging to establish inflammation models in zebrafish, allowing us to investigate the effects and underlying mechanisms of light disruption on neutrophil recruitment. Our findings reveal that under sustained light conditions (LL), neutrophil recruitment in response to caudal fin injury and otic vesicle inflammation is significantly increased. This is accompanied by elevated levels of histone (H3K18) lactylation and reactive oxygen species (ROS) content. Through ChIP-sequencing and ChIP‒qPCR analysis, we discover that H3K18 lactylation regulates the transcriptional activation of the duox gene, leading to ROS production. In turn, ROS further promote H3K18 lactylation, forming a positive feedback loop. This loop, driven by H3K18 lactylation-ROS, ultimately results in the over recruitment of neutrophils to inflammatory sites in LL conditions. Collectively, our study provides evidence of a mutual loop between histone lactylation and ROS, exacerbating neutrophil recruitment in light disorder conditions, emphasizing the significance of maintaining a proper light-dark cycle to optimize immune function.

Metformin Attenuates Neutrophil Recruitment through the H3K18 Lactylation/Reactive Oxygen Species Pathway in Zebrafish.

Beyond its well-established role in diabetes management, metformin has gained attention as a promising therapeutic for inflammation-related diseases, largely due to its antioxidant capabilities. However, the mechanistic underpinnings of this effect remain elusive. Using in vivo zebrafish models of inflammation, we explored the impact of metformin on neutrophil recruitment and the underlying mechanisms involved. Our data indicate that metformin reduces histone (H3K18) lactylation, leading to the decreased production of reactive oxygen species (ROS) and a muted neutrophil response to both caudal fin injury and otic vesicle inflammation. To investigate the precise mechanisms through which metformin modulates neutrophil migration via ROS and H3K18 lactylation, we meticulously established the correlation between metformin-induced suppression of H3K18 lactylation and ROS levels. Through supplementary experiments involving the restoration of lactate and ROS, our findings demonstrated that elevated levels of both lactate and ROS significantly promoted the inflammatory response in zebrafish. Collectively, our study illuminates previously unexplored avenues of metformin's antioxidant and anti-inflammatory actions through the downregulation of H3K18 lactylation and ROS production, highlighting the crucial role of epigenetic regulation in inflammation and pointing to metformin's potential in treating inflammation-associated conditions.

Effects of 0.4 T, 3.0 T and 9.4 T static magnetic fields on development, behaviour and immune response in zebrafish (Danio rerio).

Magnetic Resonance Imaging (MRI) is widely applied in medical diagnosis due to its excellent non-invasiveness. With the increasing intensity of static magnetic field (SMF), the safety assessment of MRI has been ongoing. In this study, zebrafish larvae were exposed to SMFs of 0.4, 3.0, and 9.4 T for 2 h (h), and we found that there was no significant difference in the number of spontaneous tail swings, heart rate, and body length of zebrafish larvae in the treatment groups. The expression of development-related genes shha, pygo1, mylz3 and runx2b in the three SMF groups was almost not significantly different from the control group. Behavior tests unveiled a notable reduction in both the average speed and duration of high-speed movements in zebrafish larvae across all three SMF groups. In addition, the 0.4 and 3.0 T SMFs increased the migration of neutrophils in caudal fin injury, and the expression of pro-inflammatory cytokines was also increased. To explore the mechanism of SMFs on zebrafish immune function, this study utilized aanat2-/- mutant fish to demonstrate the effect of melatonin (MT) involvement in SMFs on zebrafish immune function. This study provides experimental data for understanding the effects of SMFs on organisms, and also provides a new insight for exploring the relationship between magnetic fields and immune function.

Circadian clock1a coordinates neutrophil recruitment via nfe212a/duox-reactive oxygen species pathway in zebrafish.

Neutrophil recruitment to inflammatory sites appears to be an evolutionarily conserved strategy to fight against exogenous insults. However, the rhythmic characteristics and underlying mechanisms of neutrophil migration on a 24-h timescale are largely unknown. Using the advantage of in vivo imaging of zebrafish, this study explored how the circadian gene clock1a dynamically regulates the rhythmic recruitment of neutrophils to inflammatory challenges. We generated a clock1a mutant and found that neutrophil migration is significantly increased in caudal fin injury and lipopolysaccharide (LPS) injection. Transcriptome sequencing, chromatin immunoprecipitation (ChIP), and dual-luciferase reporting experiments suggest that the clock1a gene regulates neutrophil migration by coordinating the rhythmic expression of nfe212a and duox genes to control the reactive oxygen species (ROS) level. This study ultimately provides a visual model to expand the understanding of the rhythmic mechanisms of neutrophil recruitment on a circadian timescale in a diurnal organism from the perspective of ROS.

Red room temperature phosphorescence of lead halide based coordination polymer showing efficient angle-dependent polarized emission and photoelectric performance.

The development of organic-inorganic hybrid materials with long-lived room temperature phosphorescence (RTP) has attracted tremendous attention owing to their promising applications in the optoelectronic and anti-counterfeiting fields. In this work, by the selection of lead halide and electron-poor heteroaromatic molecule 1,10-phenanthroline (phen), a coordination polymer [Pb(phen)Cl2] has been synthesized under hydrothermal conditions. This complex shows an alternating arrangement of a long-range order of phen π-conjugated systems and lead halide inorganic chains as revealed by X-ray single-crystal structural analysis. This structural character and special chemical components endow this hybrid material with a rare example of red room temperature phosphorescence. Its electronic structure and electronic transition behavior were further examined by theoretical calculations. Meanwhile, the film of the complex features remarkable angle-dependent polarized emission and photoelectric performance.

An anthracene based metal-organic framework showing efficient angle-dependent polarized emission, luminescence thermometry, and photoelectronic response.

The development of luminescent metal-organic frameworks (MOFs) has attracted extensive attention due to their applications in photoelectric devices, organic light-emitting diodes (OLEDs), anti-counterfeiting, biological imaging and so on. In this work, a novel anthracene based metal-organic framework, [Cd(DCPA)(DMF)]·(H2O) (1) (H2DCPA = 9,10-di(p-carboxyphenyl)anthracene), has been successfully synthesized under solvothermal conditions. The highly ordered arrangement and special spatial conformation of the anthracene chromophore play a significant role in the photophysical properties of 1. The combination of theoretical calculations and experiments shows that the molecular orbitals have good separation for inhibiting the recombination of electrons and holes. Furthermore, the fluorescence emission of 1 can be instantaneously and reversibly tuned between blue and green at different polarizing angles. Temperature-dependent fluorescence measurements indicate a good linear relationship between the maximum emission intensity/wavelength and the temperature for efficient thermochromism and luminescence thermometry. Photoelectric measurements reveal that 1 shows high performance of photocurrent generation under light illumination. Therefore, our research affords a new perspective to extend the application of luminescent MOFs in the fields of polarized emission, thermometry and photoelectronic response.

[Clinical and Neuroimaging Analysis of 24 Cases of Sturge-Weber Syndrome].

OBJECTIVE: To analyze the clinical manifestations and neuroimaging characteristics of Sturge-Weber syndrome (SWS), to describe the manifestations of facial port-wine stains (PWS) of SWS, and to explore the screening opinions for SWS. METHODS: A retrospective analysis was performed on the general condition, clinical manifestations, and neuroimaging results of 24 SWS patients from the dermatology department of West China Hospital of Sichuan University between 2017 and 2019. Three different facial PWS distribution methods (traditional anatomical distribution, facial trigeminal nerve distribution, and facial embryological vasculature distribution) in SWS patients were Analysed. RESULTS: Among the 24 patients, 50% were male and 50% were female, with an average age of (18.9±14.0) years (range 1 to 54 years old). 12 cases were SWS type Ⅰ, and the other 12 cases were type Ⅱ. All patients had facial PWS at birth, and the facial PWS of 13 cases (54.2%) were thickened. According to the anatomical division, all the PWS involved the upper and middle face (above the oral commissure); according to the trigeminal nerve distribution, 100% (24/24) patients involve the V2 area; according to the distribution of facial embryological vasculature, 95.8% (23/24) of the patients involved frontal region. 22 patients had ophthalmic abnormalities, the most common was glaucoma (70.8%), and 4 patients had a history of epilepsy. The typical neuroimaging presentations of SWS include leptomeningeal enhancement, cortical calcification, enlarged choroid plexus, focal cerebral atrophy, abnormal intracranial vessels, and local thickening of the skull. CONCLUSION: Early intervention is recommended for facial PWS in patients with SWS , and ophthalmological screening should be performed on children with PWS found in any part of the upper and middle face after birth. Moreover, neuroimaging examination (MRI) for patients with high suspicion of SWS should be performed after 1 year old, and regular ophthalmological examination and intraocular pressure measurement is necessary.