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The de Winter electrocardiography (ECG) pattern is a sign that implies proximal left anterior descending coronary artery occlusion in patients with chest pain. We report a case of a 34‐year‐old man with a history of smoking who presented to the local emergency department with a 49 min history of chest pain. The first ECG of the patient indicated that ST‐segment elevation was noted in the lead V2–V4; 57 min later, a second ECG revealed a typical de Winter syndrome when the patient was transferred to the emergency chest pain centre of our hospital. A percutaneous coronary intervention (PCI) was performed approximately 8 h later because the patient initially refused the PCI. Acute coronary artery angiography showed that the proximal left anterior descending coronary artery was completely occluded. Our case suggests that ST‐segment elevation myocardial infarction may evolve in the direction of de Winter, which reflects a coronary thrombus in formation, so the de Winter ECG pattern should not be considered static. [ABSTRACT FROM AUTHOR]

Researchers describe four subsites in the chondroitin AC lyase from Flavobacterium heparinium complexed with oligosaccharides. Subsites

Purpose: Glutamine plays an important role in tumor metabolism and progression. This research aimed to find out how Gln exert their effects on laryngeal squamous cell carcinoma (LSCC). Methods: Cell proliferation was measured by CCK8 and EdU assay, mitochondrial bioenergetic activity was measured by mitochondrial stress tests. Gene expression profiling was revealed by RNA sequencing and validated by RT-qPCR. In LSCC patients, protein expression in tumor and adjacent tissues was examined and scored by IHC staining. RNAi was performed by stably expressed shRNA in TU177 cells. In vivo tumor growth analysis was performed using a nude mouse tumorigenicity model. Results: Gln deprivation suppressed TU177 cell proliferation, which was restored by αKG supplementation. By transcriptomic analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as the downstream target gene for Gln and αKG. In LSCC patients, the expression of CECR2 in tumors was lower than adjacent tissues. Furthermore, deficiency of CECR2 promoted tumor cell growth both in vitro and in vivo, suggesting it has tumor suppressor effects. Besides, cell proliferation inhibited by Gln withdrawal could be restored by CECR2 depletion, and the proliferation boosted by αKG supplementation could be magnified either, suggested that CECR2 feedback suppressed Gln and αKG's effect on tumor growth. Transcriptomic profiling revealed CECR2 regulated the expression of a series of genes involved in tumor progression. Conclusion: We confirmed the Gln-αKG-CECR2 axis contributes to tumor growth in LSCC. This finding provided a potential therapeutic opportunity for the use of associated metabolites as a potential treatment for LSCC. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity under the age of 40. Theca cells (TCs) play a vital role during folliculogenesis and TCs dysfunction participate in the pathogenesis of POI. Therefore, transplantation of thecal stem cells (TSCs), which are capable of self-renewal and differentiation into mature TCs, may provide a new strategy for treating POI. To investigate the feasibility, safety, and efficacy of TSCs transplantation in clinically relevant non-human primate (NHP) models, we isolate TSCs from cynomolgus monkeys, and these cells are confirmed to expand continuously and show potential to differentiate into mature TCs. In addition, engraftment of autologous TSCs into POI monkeys significantly improves hormone levels, rescues the follicle development, promotes the quality of oocytes and boosts oocyte maturation/fertilization rate. Taken together, these results for the first time suggest that autologous TSCs can ameliorate POI symptoms in primate models and shed new light on developing stem cell therapy for POI. [ABSTRACT FROM AUTHOR]

A crystallographic study of complexes of E. coli dethiobiotin synthetase and a reaction intermediate reveals that one molecule of each substrate binds to to one monomer of the enzyme. ADP and ATP analogue attach to the mononucleotide fold with the phosphate groups near the phosphate binding loop Gly8-Thr16 between beta-strand beta1 and the N-terminus of alpha-helix alpha1. Two oxygen atoms from the phosphates and oxygen atoms from the side chains of Asp54, Thr16, and Glu115 are ligands of the Mn+2 ion..

Intervertebral disc degeneration (IVDD) contributes largely to low back pain. Recent studies have highlighted the exacerbating role of diabetes mellitus (DM) in IVDD, mainly due to the influence of hyperglycemia (HG) or the accumulation of advanced glycation end products (AGEs). Vascular endothelial growth factor A (VEGFA) newly assumed a distinct impact in nonvascular tissues through mitophagy regulation. However, the combined actions of HG and AGEs on IVDD and the involved role of VEGFA remain unclear. We confirmed the potential relation between VEGFA and DM through bioinformatics and biological specimen detection. Then we observed that AGEs induced nucleus pulposus (NP) cell degeneration by upregulating cellular reactive oxygen species (ROS), and HG further aggravated ROS level through breaking AGEs-induced protective mitophagy. Furthermore, this adverse effect could be strengthened by VEGFA knockdown. Importantly, we identified that the regulation of VEGFA and mitophagy were vital mechanisms in AGEs-HG-induced NP cell degeneration through Parkin/Akt/mTOR and AMPK/mTOR pathway. Additionally, VEGFA overexpression through local injection with lentivirus carrying VEGFA plasmids significantly alleviated NP degeneration and IVDD in STZ-induced diabetes and puncture rat models. In conclusion, the findings first confirmed that VEGFA protects against AGEs-HG-induced IVDD, which may represent a therapeutic strategy for DM-related IVDD. • VEGFA expression of NP tissues was significantly downregulated in DM condition. • HG aggravates AGEs-induced NP cell degeneration which can be reversed by hVEGFA. • VEGFA maintained mitophagy through regulating mTOR-related signal pathway in NP cells. • VEGFA protects against AGEs-HG-induced NP cell degeneration and IVDD. [ABSTRACT FROM AUTHOR]