Radical-SAM dependent nucleotide dehydratase (SAND), rectification of the names of an ancient iron-sulfur enzyme using NC-IUBMB recommendations

In 1789, the influential French chemist Antoine-Laurent Lavoisier described his view of science and its langague in his book Traité élémentaire de chimie. According to the Robert Kerr’s translation it states (Lavoisier, 1790): “As ideas are preserved and communicated by means of words, it necessarily follows that we cannot improve the language of any science without at the same time improving the science itself; neither can we, on the other hand, improve a science without improving the language or nomenclature which belongs to it.” This view reminds us of Confucius’s earlier doctrine, the rectification of names (Steinkraus, 1980; Lau, 2000). Confucius believed that rectification of names is imperative. He explained (Steinkraus, 1980; Lau, 2000): “If language is incorrect, then what is said does not concord with what was meant, what is to be done cannot be affected. If what is to be done cannot be affected, then rites and music will not flourish. If rites and music do not flourish, then mutilations and lesser punishments will go astray. And if mutilations and lesser punishments go astray, then the people have nowhere to put hand or foot. Therefore the gentleman uses only such language as is proper for speech, and only speaks of what it would be proper to carry into effect. The gentleman in what he says leaves nothing to mere chance.” Inspired by these views, we make the analogy that the progress of science and the language used to describe it are two entangled electrons. This entanglement highlights the importance of introducing systemic names for enzymes using EC classification and the ever-growing problem of protein names (McDonald and Tipton, 2021). Here, we tackle one specific case of iron-sulfur ([FeS]) enzymes. We show that the language used to describe a conserved [FeS] enzyme of the innate immune system, i.e., viperin or RSAD2, is now inadequate and disentangled from its science. We discuss that the enzyme has cellular functions beyond its antiviral activity and that eukaryotic and prokaryotic enzymes catalyse the same chemical reactions. To prevent bias towards antiviral activity while studying various biochemical activities of the enzyme and using scientifically incorrect terms like “prokaryotic viperins,” we rectify the language describing the enzyme. Based on NC-IUBMB recommendations, we introduce the nomenclature S-adenosylmethionine (SAM) dependent Nucleotide Dehydratase (SAND)

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Multi-structural molecular docking (MOD) combined with molecular dynamics reveal the structural requirements of designing broad-spectrum inhibitors of SARS-CoV-2 entry to host cells

Abstract New variants of SARS-CoV-2 that can escape immune response continue to emerge. Consequently, there is an urgent demand to design small molecule therapeutics inhibiting viral entry to host cells to reduce infectivity rate. Despite numerous in silico and in situ studies, the structural requirement of designing viral-entry inhibitors effective against multiple variants of SARS-CoV-2 has yet to be described. Here we systematically screened the binding of various natural products (NPs) to six different SARS-CoV-2 receptor-binding domain (RBD) structures. We demonstrate that Multi-structural Molecular Docking (MOD) combined with molecular dynamics calculations allowed us to predict a vulnerable site of RBD and the structural requirement of ligands binding to this vulnerable site. We expect that our findings lay the foundation for in silico screening and identification of lead molecules to guide drug discovery into designing new broad-spectrum lead molecules to counter the threat of future variants of SARS-CoV-2

PSAT1 is regulated by ATF4 and enhances cell proliferation via the GSK3β/β-catenin/cyclin D1 signaling pathway in ER-negative breast cancer

Abstract Background A growing amount of evidence has indicated that PSAT1 is an oncogene that plays an important role in cancer progression and metastasis. In this study, we explored the expression and function of PSAT1 in estrogen receptor (ER)-negative breast cancer. Method The expression level of PSAT1 in breast cancer tissues and cells was analyzed using real-time-PCR (RT-PCR), TCGA datasets or immunohistochemistry (IHC). The overall survival of patients with ER-negative breast cancer stratified by the PSAT1 expression levels was evaluated using Kaplan-Meier analysis. The function of PSAT1 was analyzed using a series of in vitro assays. Moreover, a nude mouse model was used to evaluate the function of PSAT1 in vivo. qRT-PCR and western blot assays were used to evaluate gene and protein expression, respectively, in the indicated cells. In addition, we demonstrated that PSAT1 was activated by ATF4 by chromatin immunoprecipitation (ChIP) assays. Results mRNA expression of PSAT1 was up-regulated in ER-negative breast cancer. A tissue microarray that included 297 specimens of ER-negative breast cancer was subjected to an immunohistochemistry assay, which demonstrated that PSAT1 was overexpressed and predicted a poor clinical outcome of patients with this disease. Our data showed that PSAT1 promoted cell proliferation and tumorigenesis in vitro and in vivo. We further found that PSAT1 induced up-regulation of cyclin D1 via the GSK3β/β-catenin pathway, which eventually led to the acceleration of cell cycle progression. Furthermore, ATF4 was also overexpressed in ER-negative breast cancers, and a positive correlation between the ATF4 and PSAT1 mRNA levels was observed in ER-negative breast cancers. We further demonstrated that knockdown of ATF4 by siRNA reduced PSAT1 expression. Finally, chromatin immunoprecipitation (ChIP) assays showed that PSAT1 was a target of ATF4. Conclusions PSAT1, which is overexpressed in ER-negative breast cancers, is activated by ATF4 and promotes cell cycle progression via regulation of the GSK3β/β-catenin/cyclin D1 pathway

Constructing the Mo2C@MoOx Heterostructure for Improved SERS Application

Surface-enhanced Raman scattering (SERS) is a non-destructive spectra analysis technique. It has the virtues of high detectivity and sensitivity, and has been extensively studied for low-trace molecule detection. Presently, a non-noble-metal-based SERS substrate with excellent enhancement capabilities and environmental stability is available for performing advanced biomolecule detection. Herein, a type of molybdenum carbide/molybdenum oxide (Mo2C@MoOx) heterostructure is constructed, and attractive SERS performance is achieved through the promotion of the charge transfer. Experimentally, Mo2C was first prepared by calcinating the ammonium molybdate tetrahydrate and gelatin mixture in an argon atmosphere. Then, the obtained Mo2C was further annealed in the air to obtain the Mo2C@MoOx heterostructure. The SERS performance was evaluated by using a 532 nm laser as an excitation source and a rhodamine 6G (R6G) molecule as the Raman reporter. This process demonstrates that attractive SERS performance with a Raman enhancement factor (EF) of 1.445 × 108 (R6G@10−8 M) and a limit of detection of 10−8 M can be achieved. Furthermore, the mechanism of SERS performance improvement with the Mo2C@MoOx is also investigated. HRTEM detection and XPS spectra reveal that part of the Mo2C is oxidized into MoOx during the air-annealing process, and generates metal–semiconductor mixing energy bands in the heterojunction. Under the Raman laser irradiation, considerable hole–electron pairs are generated in the heterojunction, and then the hot electrons move towards MoOx and subsequently transfer to the molecules, which ultimately boosts the Raman signal intensity

Pleomorphic adenomas and mucoepidermoid carcinomas of the breast are underpinned by fusion genes

Primary pleomorphic adenomas (PAs) and mucoepidermoid carcinomas (MECs) of the breast are vanishingly rare. Here we sought to determine whether breast PAs and MECs would be underpinned by the fusion genes reported to occur in their salivary gland counterparts. Our study included three breast PAs and one breast MEC, which were subjected to RNA sequencing (PAs, n = 2; MEC, n = 1) or to Archer FusionPlex sequencing (PA, n = 1). Our analyses revealed the presence of the HMGA2-WIF1 fusion gene in breast PA3, the CTNNB1-PLAG1 fusion gene in breast PA2, and the CRTC1-MAML2 fusion gene in the breast MEC analyzed (1/1). No oncogenic fusion genes were detected in breast PA1, and no additional oncogenic fusion genes were detected in the cases studied. The presence of the fusion genes identified was validated by fluorescence in situ hybridization (n = 1), reverse transcription-PCR (n = 1), or by both methods (n = 1). Taken together, our findings indicate that PAs and MECs arising in the breast resemble their salivary gland counterparts not only phenotypically but also at the genetic level. Furthermore, our data suggest that the molecular analysis of breast PAs and MECs might constitute a useful tool to aid in their differential diagnosis

Mechanisms of ferroptosis in Alzheimer's disease and therapeutic effects of natural plant products: A review

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by massive loss of specific neurons. It is a progressive disabling, severe and fatal complex disease. Due to its complex pathogenesis and limitations of clinical treatment strategies, it poses a serious medical challenge and medical burden worldwide. The pathogenesis of AD is not clear, and its potential biological mechanisms include aggregation of soluble amyloid to form insoluble amyloid plaques, abnormal phosphorylation of tau protein and formation of intracellular neurofibrillary tangles (NFT), neuroinflammation, ferroptosis, oxidative stress and metal ion disorders. Among them, ferroptosis is a newly discovered programmed cell death induced by iron-dependent lipid peroxidation and reactive oxygen species. Recent studies have shown that ferroptosis is closely related to AD, but the mechanism remains unclear. It may be induced by iron metabolism, amino acid metabolism and lipid metabolism affecting the accumulation of iron ions. Some iron chelating agents (deferoxamine, deferiprone), chloroiodohydroxyquine and its derivatives, antioxidants (vitamin E, lipoic acid, selenium), chloroiodohydroxyquine and its derivatives Fer-1, tet, etc. have been shown in animal studies to be effective in AD and exert neuroprotective effects. This review summarizes the mechanism of ferroptosis in AD and the regulation of natural plant products on ferroptosis in AD, in order to provide reference information for future research on the development of ferroptosis inhibitors

Additional files 2: Figure S1. of PSAT1 is regulated by ATF4 and enhances cell proliferation via the GSK3β/β-catenin/cyclin D1 signaling pathway in ER-negative breast cancer

Effects of PSAT1 on the migration, invasion and apoptosis of ER-negative breast cancer cells. (A) Transwell assays were used to investigate changes in cell migration and invasion. **P < 0.01, ***P < 0.001, ****P < 0.0001. (B) Apoptosis assay based on flow cytometry shows that the suppression of PSAT1 increased the proportion of early apoptotic cells. (PDF 84 kb

Radical-SAM dependent nucleotide dehydratase (SAND), rectification of the names of an ancient iron-sulfur enzyme using NC-IUBMB recommendations

BT/Biocatalysi