Browse Articles

Polysulfur-based bulking of dynamin-related protein 1 prevents ischemic sulfide catabolism and heart failure in mice

AbstractThe presence of redox-active molecules containing catenated sulfur atoms (supersulfides) in living organisms has led to a review of the concepts of redox biology and its translational strategy. Glutathione (GSH) is the body’s primary detoxifier and antioxidant, and its oxidized form (GSSG) has been considered as a marker of oxidative status. However, we report that GSSG, but not reduced GSH, prevents ischemic supersulfide catabolism-associated heart failure in male mice by electrophilic modification of dynamin-related protein (Drp1). In healthy exercised hearts, the redox-sensitive Cys644 of Drp1 is highly S-glutathionylated. Nearly 40% of Cys644 is normally polysulfidated, which is a preferential target for GSSG-mediated S-glutathionylation. Cys644 S-glutathionylation is resistant to Drp1 depolysulfidation-dependent mitochondrial hyperfission and myocardial dysfunction caused by hypoxic stress. MD simulation of Drp1 structure and site-directed mutagenetic analysis reveal a functional interaction between Cys644 and a critical phosphorylation site Ser637, through Glu640. Bulky modification at Cys644 via polysulfidation or S-glutathionylation reduces Drp1 activity by disrupting Ser637-Glu640-Cys644 interaction. Disruption of Cys644 S-glutathionylation nullifies the cardioprotective effect of GSSG against heart failure after myocardial infarction. Our findings suggest a therapeutic potential of supersulfide-based Cys bulking on Drp1 for ischemic heart disease.

Silicon photonic MEMS switches based on split waveguide crossings

Transmission as a Key Driver of Resistance to the New Tuberculosis Drugs

Impact of Obesity on Perioperative and Clinical Outcomes After Robotic Assisted Radical Prostatectomy

Downregulation of Gldc attenuates myocardial ischemia reperfusion injury in vitro by modulating Akt and NF-κB signalings

Exploring the influence of media and social factors on altruistic behavior using the general learning model and norm activation theory

OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress

A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma

Impact of seasonal biometeorological conditions and particulate matter on asthma and COPD hospital admissions

A comprehensive analysis of advanced solar panel productivity and efficiency through numerical models and emotional neural networks

Interpret probability density functions and maximum entropy model for zinc removal in PRDC column by analyzing droplet size distribution

Multiparametric MRI along with machine learning predicts prognosis and treatment response in pediatric low-grade glioma

Multipocket synergy towards high thermoelectric performance in topological semimetal TaAs2

AbstractCharge-carrier compensation in topological semimetals amplifies the Nernst signal and simultaneously degrades the Seebeck coefficient. In this study, we report the simultaneous achievement of both a large Nernst signal and an unsaturating magneto-Seebeck coefficient in a topological nodal-line semimetal TaAs2 single crystal. The unique dual-high transverse and longitudinal thermopowers are attributed to multipocket synergy effects: the combination of a strong phonon-drag effect and the two overlapping highly dispersive conduction and valence bands with electron–hole compensation and high mobility, promising a large Nernst effect; the third Dirac band causes a large magneto-Seebeck effect. High transverse and longitudinal power factors of ~3100 and ~50 μW cm−1 K−2, respectively, are achieved, surpassing those of other topological semimetals and mainstream semiconductors. Our study presents a feasible approach for optimizing the longitudinal and transverse thermopowers in topological semimetals simultaneously and demonstrates the potential of TaAs2 for low temperature solid-state cooling.

Leveraging Old Hepatitis C Therapies

Pretreatment neutrophil-to-lymphocyte ratio is associated with immunotherapy efficacy in patients with advanced cancer: a systematic review and meta-analysis

Innovative study on chalcopyrite flotation efficiency with xanthate and ester collectors blend using response surface methodology (B.B.D): towards sustainability

A deep learning-based multi-view approach to automatic 3D landmarking and deformity assessment of lower limb

Unravelling nonclassical beam damage mechanisms in metal-organic frameworks by low-dose electron microscopy

Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product

AbstractCirculating Tumor Cells (CTCs) in blood encompass DNA, RNA, and protein biomarkers, but clinical utility is limited by their rarity. To enable tumor epitope-agnostic interrogation of large blood volumes, we developed a high-throughput microfluidic device, depleting hematopoietic cells through high-flow channels and force-amplifying magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.83 liters from seven patients with metastatic cancer. High CTC yields (mean 10,057 CTCs per patient; range 100 to 58,125) reveal considerable intra-patient heterogeneity. CTC size varies within patients, with 67% overlapping in diameter with WBCs. Paired single-cell DNA and RNA sequencing identifies subclonal patterns of aneuploidy and distinct signaling pathways within CTCs. In prostate cancers, a subpopulation of small aneuploid cells lacking epithelial markers is enriched for neuroendocrine signatures. Pooling of CNV-confirmed CTCs enables whole exome sequencing with high mutant allele fractions. High-throughput CTC enrichment thus enables cell-based liquid biopsy for comprehensive monitoring of cancer.