Nrf2-mediated redox balance alleviates LPS-induced vascular endothelial cell inflammation by inhibiting endothelial cell ferroptosis.

Ferroptosis plays an important role in inflammation and oxidative stress. Whether ferroptosis is involved in the inflammation of vascular endothelial cells and its regulation mechanism remains unclear. We estimated the correlation between serum iron ion levels and the inflammation index of 33 patients with arteriosclerosis. In vitro, HUVECs with or without ferrostatin-1 were exposed to Lipopolysaccharide. Corresponding cell models to verify the target signaling pathway. The results showed that serum iron ion levels had a significant positive correlation with N ratio, N/L, LDL level, and LDL/HDL (P < 0.05), and a negative correlation with L ratio (P < 0.05) in the arteriosclerosis patients. In vitro, ferroptosis is involved in HUVECs inflammation. Ferrostatin-1 can rescue LPS-induced HUVECs inflammation by decreasing HMGB1/IL-6/TNF-α expression. Nrf2 high expression could protect HUVECs against ferroptosis by activating the GPX4/GSH system, inhibiting ferritinophagy, and alleviating inflammation in HUVECs by inhibiting HMGB1/IL-6/TNF-α expression. It also found that Nrf2 is a key adaptive regulatory factor in the oxidative damage of HUVECs induced by NOX4 activation. These findings indicated that ferroptosis contributed to the pathogenesis of vascular endothelial cell damage by mediating endothelial cell inflammation. Nrf2-mediated redox balance in vascular inflammation may be a therapeutic strategy in vascular diseases.

Adsorption Behavior of Environmental Gas Molecules on Pristine and Defective MoSi2N4: Possible Application as Highly Sensitive and Reusable Gas Sensors.

Inspired by the recent practical application of two-dimensional (2D) nanomaterials as gas sensors, catalysts, and materials for waste gas disposal, herein, the adsorption behaviors of environmental gas molecules, including NO, CO, O2, CO2, NO2, H2O, H2S, and NH3, on the 2D pristine and defective MoSi2N4 (MSN) monolayers were systematically investigated using spin-polarized density functional theory (DFT) calculations. Our results reveal that all the gas molecules are physically adsorbed on the MSN surface with small charge transfer, but the electronic structures of NO, NO2, and O2 are obviously modified due to the in-gap states. The introduction of N vacancy on the MSN surface enhances the interaction between gas molecules and the substrate, especially for NO2 and O2. Interestingly, the adsorption type of NO and CO evolves from physisorption to chemisorption, which may be utilized in NO and CO catalytic reaction. Furthermore, the moderate adsorption strength and obvious changes in electronic properties of H2O and H2S on the defective MSN make them have promising prospects in highly sensitive and reusable gas sensors. This work offers several promising gas sensors based on the MSN monolayer and also provides a theoretical reference of other related 2D materials in the field of gas sensors, catalysts, and toxic gas disposal.

Epilepsy Associated With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes.

Objectives: The present study explored the clinical characteristics and prognostic factors of epilepsy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Methods: Thirty-four MELAS patients were included in the present study. They were diagnosed by clinical characteristics, genetic testing, muscle biopsy, and retrospective analysis of other clinical data. The patients were divided into three groups according to the effects of treatment after at least 2 years of follow-up. Results: Epilepsy was more common in male MELAS patients than in females (20/14). The age of onset ranged from 0.5 to 57 years, with an average of 22.6 years. Patients with epilepsy and MELAS had various forms of seizures. Focal seizures were the most common type affecting 58.82% of patients, and some patients had multiple types of seizures. The abnormal EEG waves were mainly concentrated in the occipital (69.57%), frontal (65.22%) and temporal lobes (47.83%). Overall, the prognosis of patients with epilepsy and MELAS was poor. Poor prognosis was associated with brain atrophy (P = 0.026), status epilepticus (P < 0.001), and use of anti-seizure medications with high mitochondrial toxicity (P = 0.015). Interpretation: Avoiding the application of anti-seizure medications with high mitochondrial toxicity, controlling seizures more actively and effectively, and delaying the occurrence and progression of brain atrophy as much as possible are particularly important to improve the prognosis of patients with MELAS and epilepsy.

Cerebral venous sinus thrombosis and subdural hematoma in a female patient with systemic lupus erythematosus: a case report and literature review.

Cerebral venous sinus thrombosis (CVST) and subdural hematoma (SDH) are extremely rare in patients with systemic lupus erythematosus (SLE), and when conditions are severe, it can endanger the life of the patients. We report a case of a 44-year-old woman who was admitted to our hospital due to multiple paroxysmal headaches, dizziness, and seizures for 20 days. In the past 2 years, she had severe thrombocytopenia. Her brain computed tomography (CT) and magnetic resonance venography (MRV) demonstrated CVST and a SDH near the right parietal occipital lobe and left temporal parietal lobe. After admission, she was eventually diagnosed with SLE based on the seizures, thrombocytopenia, positive antinuclear antibodies, and anti-ds DNA antibodies. After treatment, the patient's headaches and symptoms completely disappeared, and the myodynamia of the left limbs improved to grade 4. Her platelet count rose to 199×109/L. The second brain MRV and MRI demonstrated partial reopening of the right superior sagittal sinus, transverse sinus, and sigmoid sinus, and the improvement of bilaterally SDH, which revealed that the treatment with an anticoagulant, pulse methylprednisolone therapy, and intravenous gamma globulin was effective. We summarized possible mechanisms in this case, which can improve our understanding of CVST and SDH in SLE. And we consider that such patients should be treated as soon as possible, and the outcome can be good.

Disseminated histoplasmosis in primary Sjögren syndrome: A case report.

BACKGROUND: Sjögren syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. And histoplasmosis is an invasive mycosis caused by the saprophytic dimorphic fungus H. capsulatum. In patients with primary SS (PSS), disseminated histoplasmosis (DH) is extremely rare. CASE SUMMARY: We report a 37-year-old female patient admitted to our hospital with exacerbating fatigue, somnolence, and pancytopenia as the main symptoms. She was eventually diagnosed with DH based on pancytopenia, splenomegaly, and findings of bone marrow smears. The atypical clinical symptoms made the diagnosis process more tortuous. Unfortunately, she died of respiratory failure on the day the diagnosis was confirmed. CONCLUSION: We present a rare and interesting case of DH in a PSS patient. This case updates the geographic distribution of histoplasmosis in China, and expands the clinical manifestations of DH in PSS, highlighting the significance of constantly improving the understanding of PSS with DH.

Theoretical screening of efficient single-atom catalysts for nitrogen fixation based on a defective BN monolayer.

The electrocatalytic reduction of naturally abundant N2 to NH3 is an attractive approach to replace the Haber-Bosch nitrogen-fixation process that causes enormous energy consumption and greenhouse gas emissions. However, designing high-performance catalysts toward the electrocatalytic N2 reduction reaction (eNRR) remains one of the greatest challenges in this area. Herein, high-throughput screening of catalysts for the NRR among a series of transition metal atoms supported on a defective hexagonal boron nitride (h-BN) nanosheet is performed through spin-polarized density functional theory (DFT) computations. Strikingly, among the 18 candidates, the V/Tc atom anchored on a defective h-BN monolayer (V@BN and Tc@BN) showed good NRR activity with relatively low onset potentials. Particularly, V@BN was found to exhibit outstanding catalytic activity for the NRR via an enzymatic pathway with an extremely low overpotential of 0.25 V. The value is significantly lower than that on the Ru (0001) stepped surface that has the best NRR catalytic performance among bulk metal catalysts. The novel NRR activity of V@BN is attributed to the enhanced electrical conductivity due to V-doping, the "donation-backdonation" process for N2 activation, and the highly centralized spin-polarization on the V atom. This work not only provides a quite promising catalyst for the NRR but also provides new insights for the rational design of single-atom NRR catalysts.

Recurrent Cerebral Infarctions in Primary Sjögren Syndrome: A Case Report and Literature Review.

Recurrent cerebral infarctions are extremely rare in patients with primary Sjögren syndrome. We report a 66-year-old woman who was admitted to our hospital due to acute cerebral infarction with exacerbation of dysphagia and right-sided hemiplegia as the main symptoms. In the past 3 months, she had developed cerebral infarction twice, even though she had no risk factors for atherosclerosis. She was eventually diagnosed with primary Sjögren syndrome based on a long history of dryness of the eyes and mouth, positive anti-Ro(SSA) antibodies, and the findings of a labial salivary gland biopsy. The response to pulse methylprednisolone therapy after recurrent cerebral infarctions was poor. Thus we consider primary Sjögren syndrome patients with central nervous system involvement should be treated as soon as possible.