Purpose Ferroptosis, characterized by iron accumulation and lipid peroxidation, is a newly demonstrated form of programed cell death. Present studies reveal that ferroptosis is involved in tumor and neurodegenerative disease. Regarding its roles in the development of LN, it is least interrogated. In this study, we explored whether ferroptosis is activated and how does it change at transcriptomic level in LN. Methods 4-Hydroxynonenal (4-HNE) was stained to explore whether ferroptosis is activated. Subsequently, by using bioinformatic methods, public GSE32591 dataset was analyzed. Ferroptosis-related differentially expressed genes (FR-DEGs) were identified in both glomeruli and tubulointerstitium. Immune cell infiltration was evaluated. Correlation between FR-DEGs and infiltrated immune cells was also calculated. Finally, dataset of GSE113342, qPCR, and immunofluorescence staining were also used or performed to validate the results. Results Expression of 4-HNE was significantly increased in both glomeruli and tubulointerstitium. At transcriptomic level, 19 FR-DEGs in glomeruli and 15 FR-DEGs in tubulointerstitium including genes of iron metabolism, antioxidant system inhibitors, and ferroptosis suppressors were significantly altered in LN. Of which, LTF, CYBB, and CCL5 were upregulated and G0S2 and AKR1C1 were downregulated in both glomeruli and tubulointerstitium of LN. qPCR further validated the alteration of LTF, CYBB, CCL5, G0S2, and AKR1C1 in the whole kidney. Correlation analysis showed that CYBB positively correlated with monocyte infiltration in glomeruli and positively correlated with response to therapy. Conclusion Lipid peroxidation was aberrantly activated in LN, suggesting the activation of ferroptosis. LTF, CYBB, CCL5, G0S2, and AKR1C1, especially CYBB, might be good biomarkers of ferroptosis in LN.

Aims: Carbon monoxide poisoning is a common condition that can cause severe neurological sequelae. Previous studies have revealed that functional connectivity in carbon monoxide poisoning is abnormal under the assumption that it is resting during scanning and have focused on studying delayed encephalopathy in carbon monoxide poisoning. However, studies of functional connectivity dynamics in the acute phase of carbon monoxide poisoning may provide a more insightful perspective for understanding the neural mechanisms underlying carbon monoxide poisoning. To our knowledge, this is the first study that explores abnormal brain network dynamics in the acute phase of carbon monoxide poisoning.Methods: Combining the sliding window method and k-means algorithm, we identified four recurrent dynamic functional cognitive impairment states from resting-state functional magnetic resonance imaging data from 29 patients in the acute phase of carbon monoxide poisoning and 29 healthy controls. We calculated between-group differences in the temporal properties and intensity of dFC states, and we also performed subgroup analyses to separately explore the brain network dynamics characteristics of adult vs. child carbon monoxide poisoning groups. Finally, these differences were correlated with patients’ cognitive performance in the acute phase of carbon monoxide poisoning and coma duration.Results: We identified four morphological patterns of brain functional network connectivity. During the acute phase of carbon monoxide poisoning, patients spent more time in State 2, which is characterized by positive correlation between SMN and CEN, and negative correlation between DMN and SMN. In addition, the fractional window and mean dwell time of State 2 were positively correlated with coma duration. The subgroup analysis results demonstrated that the acute phase of childhood carbon monoxide poisoning had greater dFNC time variability than adult carbon monoxide poisoning.Conclusion: Our findings reveal that patients in the acute phase of carbon monoxide poisoning exhibit dynamic functional abnormalities. Furthermore, children have greater dFNC instability following carbon monoxide poisoning than adults. This advances our understanding of the pathophysiological mechanisms underlying acute carbon monoxide poisoning.

AimsCurrently, there are only a few studies concerning brain functional alterations after acute alcohol exposure, and the majority of existing studies attach more importance to the spatial properties of brain function without considering the temporal properties. The current study adopted sliding window to investigate the resting-state brain networks in healthy volunteers after acute alcohol intake and to explore the dynamic changes in network connectivity.Materials and methodsTwenty healthy volunteers were enrolled in this study. Blood-oxygen-level-dependent (BOLD) data prior to drinking were obtained as control, while that 0.5 and 1 h after drinking were obtained as the experimental group. Reoccurring functional connectivity patterns (states) were determined following group independent component analysis (ICA), sliding window analysis and k-means clustering. Between-group comparisons were performed with respect to the functional connectivity states fractional windows, mean dwell time, and the number of transitions.ResultsThree optimal functional connectivity states were identified. The fractional windows and mean dwell time of 0.5 h group and 1 h group increased in state 3, while the fraction window and mean dwell time of 1 h group decreased in state 1. State 1 is characterized by strong inter-network connections between basal ganglia network (BGN) and sensorimotor network (SMN), BGN and cognitive executive network (CEN), and default mode network (DMN) and visual network (VN). However, state 3 is distinguished by relatively weak intra-network connections in SMN, VN, CEN, and DMN. State 3 was thought to be a characteristic connectivity pattern of the drunk brain. State 1 was believed to represent the brain’s main connection pattern when awake. Such dynamic changes in brain network connectivity were consistent with participants’ subjective feelings after drinking.ConclusionThe current study reveals the dynamic change in resting-state brain functional network connectivity before and after acute alcohol intake. It was discovered that there might be relatively independent characteristic functional network connection patterns under intoxication, and the corresponding patterns characterize the clinical manifestations of volunteers. As a valuable imaging biomarker, dynamic functional network connectivity (dFNC) offers a new approach and basis for further explorations on brain network alterations after alcohol consumption and the alcohol-related mechanisms for neurological damage.

ObjectivesTo investigate the significance of proton magnetic resonance spectroscopy (1H-MRS) and glutamate chemical exchange saturation transfer (Glu-CEST) techniques in assessing the condition and prognosis of acute bilirubin encephalopathy patients and to understand the mechanism of nerve injury in this disease.Materials and methodsFrom September 2019 to February 2021, 31 neonates with acute bilirubin encephalopathy and 16 healthy neonates were enrolled in this study. All the quantitative results of 1H-MRS, Glu-CEST, and conventional magnetic resonance imaging (MRI) of all neonates were analyzed. The associations between statistically significant indicators of imaging and developmental quotients (DQ) were analyzed.ResultsThe 31 cases were assigned to the mild subgroup (n = 21) and moderate and severe subgroup (n = 10) according to the bilirubin-induced neurologic dysfunction (BIND) scores. The case group had elevated Cho and GABA absolute concentrations compared to the normal control group (all p < 0.05). Compared with the normal control group, the absolute concentration of GABA of the moderate and severe subgroup was significantly larger (p < 0.05). Compared with the normal control group, the Glu-CEST% values in the left basal ganglia, right thalamus, left frontal cortex and bilateral medial geniculate body of the case group was significantly larger (all p < 0.05). The moderate and severe subgroup had higher Glu-CEST% values in the left basal ganglia, right thalamus, and bilateral medial geniculate body than the normal control group (all p < 0.05). A negative association was revealed between the DQ scores and the Glu-CEST% values in the left basal ganglia (r = −0.888, p < 0.05).ConclusionThe combination of 1H-MRS and Glu-CEST techniques can monitor the intracerebral metabolite level of acute bilirubin encephalopathy and evaluate the illness severity.

BackgroundThe effect of carbon monoxide (CO) poisoning on the topology of brain functional networks is unclear, especially in children whose brains are still developing.PurposeTo investigate the topological alterations of the whole‐brain functional connectome in children with CO poisoning and characterize its relationship with disease severity.Study TypeCross‐sectional and prospective study.SubjectsA total of 26 patients with CO poisoning and 26 healthy controls.Field Strength/SequenceA 3.0 T MRI system/echo planar imaging (EPI) and 3D brain volume imaging (BRAVO) sequences.AssessmentWe used the network‐based statistics (NBS) method to explore between‐group differences in functional connectivity strength and a graph‐theoretical‐based analytic method to explore the topology of brain networks.Statistical TestsStudent's t‐test, chi‐square test, NBS, Pearson correlation coefficient, and false discovery rate correction. The statistical significance threshold was set at P < 0.05.ResultsThe case group's brain functional network topology was impaired in comparison to the control group (reduced global efficiency and small‐worldness, increased characteristic path length). According to node and edge analyses, the case group showed topologically damaged regions in the frontal lobe and basal ganglia, as well as neuronal circuits with weaker connections. Also, there was a significant correlation between the patients' coma time and the degree (r = −0.4564), efficiency (r = −0.4625), and characteristic path length (r = 0.4383) of the nodes in the left orbital inferior frontal gyrus. Carbon monoxide hemoglobin content (COHb) concentration and right rolandic operculum node characteristic path length (r = −0.3894) were significantly correlated. The node efficiency and node degree of the right middle frontal gyrus (r = 0.4447 and 0.4539) and right pallidum (r = 0.4136 and 0.4501) significantly correlated with the MMSE score.Data ConclusionThe brain network topology of CO poisoned children is damaged, which is manifested by reduced network integration and may lead to a series of clinical symptoms in patients.Evidence Level2.Technical EfficacyStage 2.