SiC IGBT degradation mechanism investigation under HV‑H3TRB tests

Ziming Wu,Zongbei Dai,Jian Zhou,Huafeng Dong,Wencan Wang,Feiwan Xie,Haoran Wang,Jiahui Yan,Xiyu Chen,Shaohua Yang,Fugen Wu 전력전자학회 2024 JOURNAL OF POWER ELECTRONICS Vol.24 No.2

The high voltage-high humidity-high temperature reverse bias (HV-H3TRB) test was utilized to evaluate the reliability of silicon carbide insulated gate bipolar transistors (SiC IGBTs). Moisture invasion often induces termination/passivation and metal corrosion. Therefore, the HV-H3TRB test is generally used to assess termination / passivation robustness. However, under the HV-H3TRB test conditions, gate quality degradation may occur. In this study, the dominant degradation mechanism of SiC IGBTs was investigated. The changes of the most sensitive static characteristics (e.g., threshold voltage, breakdown voltage, and leakage current) were recorded. The threshold voltage decreased and leakage current increased substantially after > 1000 h of HV-H3TRB tests under 85 ℃/85% RH climate conditions. Capacitance-voltage (C-V) curve measurements indicated that the mobile ions at the SiC/SiO2 interface or in the gate oxide likely caused the threshold-voltage instability in the SiC IGBTs after the HV-H3TRB tests. This instability can be recovered by applying a negative gate bias. Subsequent failure analysis confirmed no corrosion of metals or termination/passivation in the device, which indicates the robustness of the passivation (consisting of phosphor-silicate glass and Si3N4). Therefore, the gate quality appears to be a significant reliability risk for SiC IGBTs under high humidity, high temperature, and high voltage conditions.

Influence of thermophilic microorganism on non-volatile metabolites during high-temperature pile-fermentation of Chinese dark tea based on metabolomic analysis

Wen Zhu,Wenfeng Wang,Wencan Xu,Shuang Wu,Wenjun Chen,Youyi Huang,Shengpeng Wang 한국식품과학회 2022 Food Science and Biotechnology Vol.31 No.7

Pile-fermentation is a critical procedure for producing Chinese dark tea, during which thermophilic microorganisms would play an irreplaceable role. However, there have been little researches on the influences of thermophilic microorganism pile-fermentation (TMPF) in high-temperature of Chinese dark tea. Thus, we conducted high-performance liquid chromatography and nontargeted metabolomic to analyze the non-volatile metabolites of TMPF. Our results discovered that the amounts of ( −)-epigallocatechin gallate, ( −)-epigallocatechin, ( −)-epicatechin gallate, and ( −)-epicatechin were decreased significantly (p < 0.05) after TMPF. By using nontargeted metabolomic analysis, a total of 1733 ion features were detected. KEGG pathway enrichment analysis showed that TMPF had a significant impact on caffeine metabolism. Also, theophylline, 3-methylxanthine, and 1,3,7-trimethyluric acid were increased significantly after TMPF, which suggested that demethylation and oxidation reaction might be the main pathways of caffeine metabolism. This study provides a better understanding of the mechanism of TMPF during high-temperature for Chinese dark tea and lays a foundation for further research.

MD2 blockade prevents modified LDL-induced retinal injury in diabetes by suppressing NADPH oxidase-4 interaction with Toll-like receptor-4

Chen Huaicheng,Yan Tao,Song Zongming,Ying Shilong,Wu Beibei,Ju Xin,Yang Xi,Qu Jia,Wu Wencan,Zhang Zongduan,Wang Yi 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

Modified LDL-induced inflammation and oxidative stress are involved in the pathogenesis of diabetic retinopathy. Recent studies have also shown that modified LDL activates Toll-like receptor 4 (TLR4) to mediate retinal injury. However, the mechanism by which modified LDL activates TLR4 and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2) are not known. In this study, we inhibited MD2 with the chalcone derivatives L2H17 and L6H21 and showed that MD2 blockade protected retinal Müller cells against highly oxidized glycated-LDL (HOG-LDL)-induced oxidative stress, inflammation, and apoptosis. MD2 inhibition reduced oxidative stress by suppressing NADPH oxidase-4 (NOX4). Importantly, HOG-LDL activated TLR4 and increased the interaction between NOX4 and TLR4. MD2 was required for the activation of these pathways, as inhibiting MD2 prevented the association of NOX4 with TLR4 and reduced NOX4-mediated reactive oxygen species production and TLR4-mediated inflammatory factor production. Furthermore, treatment of diabetic mice with L2H17 significantly reduced LDL extravasation in the retina and prevented retinal dysfunction and apoptosis by suppressing the TLR4/MD2 pathway. Our findings provide evidence that MD2 plays a critical role in mediating modified LDL-induced cell injury in the retina and suggest that targeting MD2 may be a potential therapeutic strategy.

Single-cell characterization of macrophages in uveal melanoma uncovers transcriptionally heterogeneous subsets conferring poor prognosis and aggressive behavior

Li Ke,Sun Lanfang,Wang Yanan,Cen Yixin,Zhao Jingting,Liao Qianling,Wu Wencan,Sun Jie,Zhou Meng 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Uveal melanoma (UM) is the most frequent primary intraocular malignancy with high metastatic potential and poor prognosis. Macrophages represent one of the most abundant infiltrating immune cells with diverse functions in cancers. However, the cellular heterogeneity and functional diversity of macrophages in UM remain largely unexplored. In this study, we analyzed 63,264 single-cell transcriptomes from 11 UM patients and identified four transcriptionally distinct macrophage subsets (termed MΦ-C1 to MΦ-C4). Among them, we found that MΦ-C4 exhibited relatively low expression of both M1 and M2 signature genes, loss of inflammatory pathways and antigen presentation, instead demonstrating enhanced signaling for proliferation, mitochondrial functions and metabolism. We quantified the infiltration abundance of MΦ-C4 from single-cell and bulk transcriptomes across five cohorts and found that increased MΦ-C4 infiltration was relevant to aggressive behaviors and may serve as an independent prognostic indicator for poor outcomes. We propose a novel subtyping scheme based on macrophages by integrating the transcriptional signatures of MΦ-C4 and machine learning to stratify patients into MΦ-C4-enriched or MΦ-C4-depleted subtypes. These two subtypes showed significantly different clinical outcomes and were validated through bulk RNA sequencing and immunofluorescence assays in both public multicenter cohorts and our in-house cohort. Following further translational investigation, our findings highlight a potential therapeutic strategy of targeting macrophage subsets to control metastatic disease and consistently improve the outcome of patients with UM.

Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis

Zhang Weifeng,Li Gaocai,Luo Rongjin,Lei Jie,Song Yu,Wang Bingjin,Ma Liang,Liao Zhiwei,Ke Wencan,Liu Hui,Hua Wenbin,Zhao Kangcheng,Feng Xiaobo,Wu Xinghuo,Zhang Yukun,Wang Kun,Yang Cao 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Low back pain (LBP) is a major musculoskeletal disorder and the socioeconomic problem with a high prevalence that mainly involves intervertebral disc (IVD) degeneration, characterized by progressive nucleus pulposus (NP) cell death and the development of an inflammatory microenvironment in NP tissue. Excessively accumulated cytosolic DNA acts as a damage-associated molecular pattern (DAMP) that is monitored by the cGAS-STING axis to trigger the immune response in many degenerative diseases. NLRP3 inflammasome-dependent pyroptosis is a type of inflammatory programmed death that promotes a chronic inflammatory response and tissue degeneration. However, the relationship between the cGAS-STING axis and NLRP3 inflammasome-induced pyroptosis in the pathogenesis of IVD degeneration remains unclear. Here, we used magnetic resonance imaging (MRI) and histopathology to demonstrate that cGAS, STING, and NLRP3 are associated with the degree of IVD degeneration. Oxidative stress induced cGAS-STING axis activation and NLRP3 inflammasome-mediated pyroptosis in a STING-dependent manner in human NP cells. Interestingly, the canonical morphological and functional characteristics of mitochondrial permeability transition pore (mPTP) opening with the cytosolic escape of mitochondrial DNA (mtDNA) were observed in human NP cells under oxidative stress. Furthermore, the administration of a specific pharmacological inhibitor of mPTP and self-mtDNA cytosolic leakage effectively reduced NLRP3 inflammasome-mediated pyroptotic NP cell death and microenvironmental inflammation in vitro and degenerative progression in a rat disc needle puncture model. Collectively, these data highlight the critical roles of the cGAS-STING-NLRP3 axis and pyroptosis in the progression of IVD degeneration and provide promising therapeutic approaches for discogenic LBP.