ObjectivesTo identify the cooperation and impact of authors, countries, institutions, and journals, evaluate the knowledge base, find the hotspot trends, and detect the emerging topics regarding ferroptosis research.MethodsThe articles and reviews related to ferroptosis were obtained from the Web of Science Core Collection on November 1, 2020. Two scientometric software (CiteSpace 5.7 and VOSviewer 1.6.15) were used to perform bibliometric and knowledge-map analysis.ResultsA total of 1,267 papers were included, in 466 academic journals by 6,867 authors in 438 institutions from 61 countries/regions. The ferroptosis-related publications were increasing rapidly. Cell Death & Disease published the most papers on ferroptosis, while Cell was the top co-cited journal, publication journals and co-cited journals were major in the molecular and biology fields. The United States and China were the most productive countries; meanwhile, the University of Pittsburgh, Columbia University and Guangzhou Medical University were the most active institutions. Brent R Stockwell published the most papers, while Scott J Dixon had the most co-citations; simultaneously, active cooperation existed in ferroptosis researchers. Ten references on reviews, mechanisms, and diseases were regarded as the knowledge base. Five main aspects of ferroptosis research included regulation mechanisms, nervous system injury, cancer, relationships with other types of cell death, and lipid peroxidation. The latest hotspots were nanoparticle, cancer therapy, iron metabolism, and in-depth mechanism. Notably Nrf2 might have turning significance. The emerging topics on ferroptosis research were the further molecular mechanism of ferroptosis and the wider application of ferroptosis-related disease with advanced technology.ConclusionThis study performed a full overview of the ferroptosis research using bibliometric and visual methods. The information would provide helpful references for scholars focusing on ferroptosis.

The differently expressed lncRNAs may be associated with the pathogenesis of OA. Further functional studies are critical to confirming the function of lncRNAs in OA and to exploring new potential targets for therapy.

This paper analyzes the impact of higher-order inference (HOI) on the task of coreference resolution. HOI has been adapted by almost all recent coreference resolution models without taking much investigation on its true effectiveness over representation learning. To make a comprehensive analysis, we implement an endto-end coreference system as well as four HOI approaches, attended antecedent, entity equalization, span clustering, and cluster merging, where the latter two are our original methods. We find that given a high-performing encoder such as SpanBERT, the impact of HOI is negative to marginal, providing a new perspective of HOI to this task. Our best model using cluster merging shows the Avg-F1 of 80.2 on the CoNLL 2012 shared task dataset in English.

To evaluate the repeatability of corneal biomechanical parameters in normal and keratoconus eyes, and explore factors that affects the repeatability, and further assess the diagnostic ability of new parameters. Seventy-seven keratoconus eyes of 47 patients and 77 right eyes of 77 normal subjects were recruited in current study. All participants received three repeated measurements with 2 to 5 minutes interval. The interclass correlation coefficient (ICC), Cronbach’ α and repeatability coefficient (RC) were evaluated. The liner regression analysis was used to identify factors that affect the repeatability, and linear mixed effects model was performed to compare the parameters differences. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of new parameters. Eighteen parameters in normal eyes and twenty-two parameters in keratoconus eyes showed excellent repeatability (ICC ≥ 0.90). Age, axial measurement (AL), spherical equivalent, astigmatism, gender, mean keratometry (Kmean), intraocular pressure (IOP) and central corneal thickness (CCT) could affect the repeatability of new Corvis ST parameters. Compared with normal eyes, the Ambrósio’s Relational Thickness horizontal (ARTh), biomechanical corrected IOP (bIOP), stiffness parameter at first applanation (SP A1) were low and the Max Inverse Radius, deformation amplitude (DA) Ratio Max [2 mm], Pachy Slope, DA Ratio Max [1 mm], Integrated Radius and Corvis Biomechanical Index (CBI) were high in keratoconus eyes (All P < 0.05). Both ARTh and CBI had high Youden index (0.870), and the corresponding cut-off values were 379.29 and 0.44. The repeatability of Corvis ST parameters was acceptable both in normal and keratoconus eyes, and new parameters could effectively diagnose keratoconus eyes from normal eyes.

MYCN amplification is tightly associated with the poor prognosis of pediatric neuroblastoma (NB). The regulation of NB cell death by MYCN represents an important aspect, as it directly contributes to tumor progression and therapeutic resistance. However, the relationship between MYCN and cell death remains elusive. Ferroptosis is a newly identified cell death mode featured by lipid peroxide accumulation that can be attenuated by GPX4, yet whether and how MYCN regulates ferroptosis are not fully understood. Here, we report that MYCN-amplified NB cells are sensitive to GPX4-targeting ferroptosis inducers. Mechanically, MYCN expression reprograms the cellular iron metabolism by upregulating the expression of TFRC, which encodes transferrin receptor 1 as a key iron transporter on the cell membrane. Further, the increased iron uptake promotes the accumulation of labile iron pool, leading to enhanced lipid peroxide production. Consistently, TFRC overexpression in NB cells also induces selective sensitivity to GPX4 inhibition and ferroptosis. Moreover, we found that MYCN fails to alter the general lipid metabolism and the amount of cystine imported by System Xc(−) for glutathione synthesis, both of which contribute to ferroptosis in alternative contexts. In conclusion, NB cells harboring MYCN amplification are prone to undergo ferroptosis conferred by TFRC upregulation, suggesting that GPX4-targeting ferroptosis inducers or TFRC agonists can be potential strategies in treating MYCN-amplified NB.

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L-asparaginase, which catalyses the hydrolysis of L-asparagine to L-aspartate, has attracted the attention of researchers due to its expanded applications in medicine and the food industry. In this study, a novel thermostable L-asparaginase from Pyrococcus yayanosii CH1 was cloned and over-expressed in Bacillus subtilis 168. To obtain thermostable L-asparaginase mutants with higher activity, a robust high-throughput screening process was developed specifically for thermophilic enzymes. In this process, cell disruption and enzyme activity assays are simultaneously performed in 96-deep well plates. By combining error-prone PCR and screening, six brilliant positive variants and four key amino acid residue mutations were identified. Combined mutation of the four residues showed relatively high specific activity (3108 U/mg) that was 2.1 times greater than that of the wild-type enzyme. Fermentation with the mutant strain in a 5-L fermenter yielded L-asparaginase activity of 2168 U/mL.

Steroid-associated osteonecrosis (SAON) is one of the common complications of clinical glucocorticoid (GC) administration, with osteocyte apoptosis appearing as the primary histopathological lesion. However, the precise mechanism underlying SAON remains unknown. Epigenetic modification may be a major cause of SAON. Recently, cumulative research revealed that Ten-Eleven Translocation (TET) proteins can catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and then alter the epigenetic state of DNA. Here, we report that TET3-5hmC was upregulated in the femoral head tissues of SAON patients and MLO-Y4 cells with dexamethasone (Dex) treatment. Knockdown of TET3 in MLO-Y4 cells decreased 5hmC enrichment and rescued Dex-induced apoptosis. Meanwhile, the local intramedullary injection of TET3 siRNA in Sprague-Dawley rats abrogated GC-induced osteocyte apoptosis, histopathological changes, abnormal MRI signals, and bone microstructure declines in the femoral head in vivo. Moreover, a hydroxymethylated DNA immunoprecipitation (hMeDIP)-chip analysis of Dex-treated osteocytes revealed 456 different 5hmC-enriched genes. The Akt pathway was found to mediate the functional effect of Dex-induced dynamic 5hmC change; this was further verified in clinical samples. The loss of TET3 in MLO-Y4 cells abrogated Dex-induced Akt signaling pathway inhibition. Therefore, our data for the first time identify the effect of TET3-5hmC on the Akt pathway and the necessity of this signaling cascade in SAON, identifying a new potential therapeutic target. © 2016 American Society for Bone and Mineral Research.