HuMSC-EVs Protect Endothelial Cells Against Hypoxia/Reoxygenation Injury by Inhibiting the Pannexin 1/p38-MAPK Pathway.

Vascular endothelial cell dysfunction plays an important role in myocardial ischemia-reperfusion (I/R) injury, and pannexin 1 (Panx1), an ATP-permeable channel, is closely associated with the pathophysiological processes of I/R injury. The purpose of this study was to investigate the protective effects of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (HuMSC-EVs) and the underlying mechanism in a model of I/R injury. For the cellular model of I/R injury, human umbilical vein endothelial cells (HuVECs) were exposed to hypoxia/reoxygenation (H/R) conditions. The model cells were then treated with HuMSC-EVs, and the effects on cell survival and specific signaling activities were observed. The results showed that after H/R exposure, Panx1 expression and other markers of cellular damage were increased in HuVECs. However, treatment with HuMSC-EVs inhibited the H/R-induced increase in Panx1 expression and improved HuVEC survival. Mechanistically, HuMSC-EVs were found to inhibit the p38 mitogen-activated protein kinase (MAPK)-dependent apoptosis pathway, as evidenced by increased Bcl2 expression and reductions in p38 MAPK phosphorylation, Bax expression, and cleaved-caspase 3 expression. Together our data suggest that HuMSC-EVs alleviate H/R-induced apoptosis among HuVECs by inhibiting activity of the Panx1/p38-MAPK-dependent apoptosis pathway.

Classification of diabetic maculopathy based on optical coherence tomography images using a Vision Transformer model.

PURPOSE: To develop a Vision Transformer model to detect different stages of diabetic maculopathy (DM) based on optical coherence tomography (OCT) images. METHODS: After removing images with poor quality, a total of 3319 OCT images were extracted from the Eye Center of the Renmin Hospital of Wuhan University and randomly split the images into training and validation sets in a 7:3 ratio. All macular cross-sectional scan OCT images were collected retrospectively from the eyes of DM patients from 2016 to 2022. One of the OCT stages of DM, including early diabetic macular oedema (DME), advanced DME, severe DME and atrophic maculopathy, was labelled on the collected images, respectively. A deep learning (DL) model based on Vision Transformer was trained to detect four OCT grading of DM. RESULTS: The model proposed in our paper can provide an impressive detection performance. We achieved an accuracy of 82.00%, an F1 score of 83.11%, an area under the receiver operating characteristic curve (AUC) of 0.96. The AUC for the detection of four OCT grading (ie, early DME, advanced DME, severe DME and atrophic maculopathy) was 0.96, 0.95, 0.87 and 0.98, respectively, with an accuracy of 90.87%, 89.96%, 94.42% and 95.13%, respectively, a precision of 88.46%, 80.31%, 89.42% and 87.74%, respectively, a sensitivity of 87.03%, 88.18%, 63.39% and 89.42%, respectively, a specificity of 93.02%, 90.72%, 98.40% and 96.66%, respectively and an F1 score of 87.74%, 84.06%, 88.18% and 88.57%, respectively. CONCLUSION: Our DL model based on Vision Transformer demonstrated a relatively high accuracy in the detection of OCT grading of DM, which can help with patients in a preliminary screening to identify groups with serious conditions. These patients need a further test for an accurate diagnosis, and a timely treatment to obtain a good visual prognosis. These results emphasised the potential of artificial intelligence in assisting clinicians in developing therapeutic strategies with DM in the future.

Moxibustion at 'Danzhong' (RN17) and 'Guanyuan' (RN4) for fatigue symptom in patients with depression: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Fatigue is one of the most prevalent and debilitating symptoms of major depressive disorder (MDD). The effective management of depression-related fatigue has an important impact on the patient's abilities, functioning, and quality of life (QOL). Moxibustion has been widely used in Traditional Chinese Medicine to manage fatigue. Recent studies have also demonstrated that moxibustion is effective for treating cancer-related fatigue and chronic fatigue syndrome. However, there is not sufficient data supporting the effect of moxibustion for depression-related fatigue. Therefore, this randomized, assessor-blinded, wait-list controlled trial is designed to evaluate the effectiveness, safety, and feasibility of moxibustion treatment for depression-related fatigue. METHODS: One hundred and seventy-six participants who meet the diagnostic criteria for depression in the International Classification of Diseases, tenth revision (ICD-10), and who also have a score of ≥1 on the 13 item of the Hamilton Depression Rating Scale-17 (HAMD-17), will be enrolled. At study entry, participants will undergo anti-depressant treatment for at least 1 month. Then those who still have a score of ≥1 on the 13 item of the HAMD-17 will be randomly allocated to either a moxibustion group or wait-list control group in a ratio of 1:1. Anti-depressants will be provided for both groups during the whole process of the study period. Participants in the moxibustion group will undergo 14 sessions of moxibustion (over 2 weeks) with anti-depressant treatment, and participants in the wait-list control group will receive only anti-depressant treatment. Subsequently, participants in the moxibustion group will be followed-up for 4 weeks. The primary outcome measure will be the Fatigue Severity Scale (FSS). The secondary outcome measure will be the HAMD-17. Safety will be assessed by monitoring adverse events during the study. Trial feasibility will also be assessed in this study. DISCUSSION: The results of this study may provide evidence for the efficacy of moxibustion as an adjunct to antidepressants for depression-related fatigue, and promote a more widespread foundation for the selection of moxibustion in the clinical setting as well as for future research in moxibustion therapy. TRIAL REGISTRATION: This study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1800016905).

Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARγ-mediated pathway in bladder cancer.

Tumor cells rely on aerobic glycolysis as their main energy resource (Warburg effect). Recent research has highlighted the importance of lipid metabolism in tumor progression, and certain cancers even turn to fatty acids as the main fuel. Related studies have identified alterations of fatty acid metabolism in human bladder cancer (BCa). Our microarray analysis showed that fatty acid metabolism was activated in BCa compared with normal bladder. The free fatty acid (FFA) level was also increased in BCa compared with paracancerous tissues. Inhibition of fatty acid oxidation (FAO) with etomoxir caused lipid accumulation, decreased adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) levels, suppressed BCa cell growth in vitro and in vivo, and reduced motility of BCa cells via affecting epithelial-mesenchymal transition (EMT)-related proteins. Furthermore, etomoxir induced BCa cell cycle arrest at G0/G1 phase through peroxisome proliferator-activated receptor (PPAR) γ-mediated pathway with alterations in fatty acid metabolism associated gene expression. The cell cycle arrest could be reversed by PPARγ antagonist GW9662. Taken together, our results suggest that inhibition of FAO with etomoxir may provide a novel avenue to investigate new therapeutic approaches to human BCa.

Coupled electro-thermal field in a high current electrolysis cell or liquid metal batteries.

Coupled electro-thermal field exists widely in chemical batteries and electrolysis industry. In this study, a three-dimensional numerical model, which is based on the finite-element software ANSYS, has been built to simulate the electro-thermal field in a magnesium electrolysis cell. The adjustment of the relative position of the anode and cathode can change the energy consumption of the magnesium electrolysis process significantly. Besides, the current intensity has a nonlinear effect on heat balance, and the effects of heat transfer coefficients, electrolysis and air temperature on the heat balance have been released to maintain the thermal stability in a magnesium electrolysis cell. The relationship between structure as well as process parameters and electro-thermal field has been obtained and the simulation results can provide experience for the scale-up design in liquid metal batteries.

Reduced paralimbic system gray matter volume in schizophrenia: Correlations with clinical variables, symptomatology and cognitive function.

BACKGROUND: Psychopathy is associated with dysfunction in regions that compose the paralimbic system, such as the orbitofrontal cortex (OFC), insular cortex (IC), temporal pole (TP), parahippocampal gyrus (PHG) and cingulate cortex (CC). However, findings of structural alterations in these regions are inconsistent in schizophrenia, and correlations between paralimbic system measures and symptomatology and cognitive function have not been investigated. METHOD: 93 patients with schizophrenia and 99 healthy controls received structural magnetic resonance imaging and clinical and cognitive assessment. We compared gray matter volume (GMV) between the two groups using voxel-based morphometry, and evaluated correlations between abnormal GMVs and clinical variables, symptomatology and cognitive function. The assessment of cognition included measures of processing speed, verbal fluency and memory. RESULTS: Patients with schizophrenia demonstrated significant GMV decreases in the paralimbic system, including bilateral OFC, IC and TP (p < 0.05, FWE corrected). GMV decreases were also observed in bilateral superior temporal gyri (STG). The GMVs in bilateral OFC, left IC, left TP and bilateral STG were positively correlated with processing speed, and the GMVs in bilateral OFC were positively correlated with memory function in all participants. In our patient group, the GMV deficits were also associated with earlier age of onset, longer duration of illness, greater number of hospitalizations and more severe positive symptoms. CONCLUSIONS: GMVs in the paralimbic system were significantly reduced in schizophrenia, and these abnormalities were correlated with clinical variables, symptomatology and cognitive function. These results suggest the paralimbic system plays an important role in the pathophysiology of schizophrenia.

Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2.

To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 × 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 × 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 × 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 × 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 × 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 × 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia.