Catalytic activity of Setd2 is essential for embryonic development in mice: establishment of a mouse model harboring patient-derived Setd2 mutation.

SETD2 is the only enzyme responsible for transcription-coupled histone H3 lysine 36 trimethylation (H3K36me3). Mutations in SETD2 cause human diseases including cancer and developmental defects. In mice, Setd2 is essential for embryonic vascular remodeling.

Threonine dehydrogenase regulates neutrophil homeostasis but not H3K4me3 levels in zebrafish.

l-threonine dehydrogenase (Tdh) is an enzyme that links threonine metabolism to epigenetic modifications and mitochondria biogenesis. In vitro studies show that it is critical for the regulation of trimethylation of histone H3 lysine 4 (H3K4me3) levels and cell fate determination of mouse embryonic stem cells (mESCs). However, whether Tdh regulates a developmental process in vivo and, if it does, whether it also primarily regulates H3K4me3 levels in this process as it does in mESCs, remains elusive.

ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation.

The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning. Zinc Finger SWIM-Type Containing 4 (zswim4) is expressed in the Spemann-Mangold organizer at the onset of Xenopus gastrulation and is then enriched in the developing neuroectoderm at the mid-gastrula stages. Knockdown or knockout of zswim4 causes ventralization.

A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors.

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1.

Reproductive Performance of Zi-Goose Promoted by Red Color Illumination.

The color of light affects the reproductive performance of poultry, but it is not clear what efficient illumination strategy could be adopted to improve the reproductive performance of Zi-goose. Red light can increase the average weekly egg production rate, egg production, and qualified production. It can increase the serum GnRH level and decrease the serum PRL, MT, and T4 levels.

An Optimized Proteomics Approach Reveals Novel Alternative Proteins in Mouse Liver Development.

Alternative ORFs (AltORFs) are unannotated sequences in genome that encode novel peptides or proteins named alternative proteins (AltProts). Although ribosome profiling and bioinformatics predict a large number of AltProts, mass spectrometry as the only direct way of identification is hampered by the short lengths and relative low abundance of AltProts. There is an urgent need for improvement of mass spectrometry methodologies for AltProt identification.

Airway microecology in rifampicin-resistant and rifampicin-sensitive pulmonary tuberculosis patients.

Background: Pulmonary tuberculosis is a chronic infectious disease of the respiratory system. It is still one of the leading causes of death from a single infectious disease, but it has been stuck in the study of a single pathogen. Recent studies have shown that many diseases are associated with disruption of the native microbiota.

A direct comparison between AML1-ETO and ETO2-GLIS2 leukemia fusion proteins reveals context-dependent binding and regulation of target genes and opposite functions in cell differentiation.

The ETO-family transcriptional corepressors, including ETO, ETO2, and MTGR1, are all involved in leukemia-causing chromosomal translocations. In every case, an ETO-family corepressor acquires a DNA-binding domain (DBD) to form a typical transcription factor-the DBD binds to DNA, while the ETO moiety manifests transcriptional activity. A directly comparative study of these "homologous" fusion transcription factors may clarify their similarities and differences in regulating transcription and leukemogenesis.

Profiling the Bisecting N-acetylglucosamine Modification in Amniotic Membrane via Mass Spectrometry.

Bisecting N-acetylglucosamine (GlcNAc), a GlcNAc linked to the core β-mannose residue via a β1,4 linkage, is a special type of N-glycosylation that has been reported to be involved in various biological processes, such as cell adhesion and fetal development. This N-glycan structure is abundant in human trophoblasts, which is postulated to be resistant to natural killer cell-mediated cytotoxicity, enabling a mother to nourish a fetus without rejection. In this study, we hypothesized that the human amniotic membrane, which serves as the last barrier for the fetus, may also express bisected-type glycans.

Nonplanar Helicene Benzo[4]Helicenium for the Precise Treatment of Renal cell Carcinoma.

Immune and targeted therapy are becoming the first-line treatment for renal cell carcinoma (RCC). However, therapeutic outcomes are limited due to the low efficiency and side effect. Here, it is found that helicenes are able to exhibit an anticancer capability through changing the molecular structure from planar to nonplanar.

The Small Open Reading Frame-Encoded Peptides: Advances in Methodologies and Functional Studies.

Small open reading frames (sORFs) are an important class of genes with less than 100 codons. They were historically annotated as noncoding or even junk sequences. In recent years, accumulating evidence suggests that sORFs could encode a considerable number of polypeptides, many of which play important roles in both physiology and disease pathology.

Thioredoxin-1 mediates neuroprotection of Schisanhenol against MPP-induced apoptosis via suppression of ASK1-P38-NF-κB pathway in SH-SY5Y cells.

Oxidative stress-induced dopaminergic neuronal loss and apoptosis play a crucial role in the pathogenesis of Parkinson's disease (PD), and as a vital antioxidant protein, thioredoxin (Trx) exerts neuroprotection against PD. In this study, we investigated the effect of Schisanhenol (Sal), an active component from a traditional Chinese herb Schisandra rubriflora (Franch.), on MPP-induced apoptosis and its association with thioredoxin-1 (Trx1) in SH-SY5Y cells.

Selective and competitive functions of the AAR and UPR pathways in stress-induced angiogenesis.

The amino acid response (AAR) and unfolded protein response (UPR) pathways converge on eIF2α phosphorylation, which is catalyzed by Gcn2 and Perk, respectively, under different stresses. This close interconnection makes it difficult to specify different functions of AAR and UPR. Here, we generated a zebrafish model in which loss of threonyl-tRNA synthetase (Tars) induces angiogenesis dependent on Tars aminoacylation activity.

Downregulation of miR-142a Contributes to the Enhanced Anti-Apoptotic Ability of Murine Chronic Myelogenous Leukemia Cells.

Background: Leukemic stem cell (LSC) is thought to be responsible for chronic myelogenous leukemia (CML) initiation and relapse. However, the inherent regulation of LSCs remains largely obscure. Herein, we integratedly analyzed miRNA and gene expression alterations in bone marrow (BM) LinSca1c-Kit cells (LSKs) of a tet-off inducible CML mouse model, Scl/tTA-BCR/ABL (BA).

The trans-omics landscape of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill.

An Integrated Approach for Discovering Noncanonical MHC-I Peptides Encoded by Small Open Reading Frames.

MHC-I peptides are a group of important immunopeptides presented by major histocompatibility complex (MHC) on the cell surface for immune recognition. The majority of reported MHC-I peptides are derived from protein coding sequences, and noncanonical peptides translated from small open reading frames (sORF) are largely unknown due to the lack of accurate and sensitive detection methods. Herein we report an efficient approach that implements complementary bioinformatic strategies to improve the identification of noncanonical MHC-I peptides.

Intra-heterogeneity in transcription and chemoresistant property of leukemia-initiating cells in murine Setd2 acute myeloid leukemia.

Background: Heterogeneity of leukemia-initiating cells (LICs) is a major obstacle in acute myeloid leukemia (AML) therapy. Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathogenicity in the same individual is a common feature in AML. However, the functional heterogeneity including the drug response of coexistent LICs remains unclear.

D283 Med, a Cell Line Derived from Peritoneal Metastatic Medulloblastoma: A Good Choice for Missing Protein Discovery.

Since the Chromosome-Centric Human Proteome Project (C-HPP) was launched in 2010, many techniques have been adopted for the discovery of missing proteins (MPs). Because of these efforts, only 1481 MPs remained as of July 2020; however, by relying only on technique optimization, researchers have reached a bottleneck in MP discovery. Protein expression is tissue- or cell-type-dependent.

knockout zebrafish is viable and fertile: differential and developmental stress-related requirements for Setd2 and histone H3K36 trimethylation in different vertebrate animals.

Setd2 is the only enzyme that catalyzes histone H3 lysine 36 trimethylation (H3K36me3) on virtually all actively transcribed protein-coding genes, and this mechanism is evolutionarily conserved from yeast to human. Despite this widespread and conserved activity, Setd2 and H3K36me3 are dispensable for normal growth of yeast but are absolutely required for mammalian embryogenesis, such as oocyte maturation and embryonic vasculogenesis in mice, raising a question of how the functional requirements of Setd2 in specific developmental stages have emerged through evolution. Here, we explored this issue by studying the essentiality and function of Setd2 in zebrafish.

A Reliable Prognosis Approach for Degradation Evaluation of Rolling Bearing Using MCLSTM.

Prognostics and health management technology (PHM), a measure to ensure the reliability and safety of the operation of industrial machinery, has attracted attention and application adequately. However, how to use the monitored information to evaluate the degradation of rolling bearings is a significant issue for its predictive maintenance and autonomic logistics. This work presents a reliable health prognosis approach to estimate the health indicator (HI) and remaining useful life (RUL) of rolling bearings.

SETD2 deficiency accelerates MDS-associated leukemogenesis via S100a9 in NHD13 mice and predicts poor prognosis in MDS.

SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML).

Exploration of Missing Proteins by a Combination Approach to Enrich the Low-Abundance Hydrophobic Proteins from Four Cancer Cell Lines.

The mission of the Chromosome-Centric Human Proteome Project (C-HPP) to discover missing proteins (MPs) has become increasingly difficult due to the remaining low-abundance, high-hydrophobicity, or low-molecular-weight MPs. We have reported two approaches to resolve these identification problems for the low-abundance and high-hydrophobicity MPs, respectively. In this study, to improve the identification of low-abundance MPs with high hydrophobicity, we combined two approaches and obtained MPs from several different cancer cell lines.

Selective Killing of Cancer Cells by Nonplanar Aromatic Hydrocarbon-Induced DNA Damage.

A large number of current chemotherapeutic agents prevent the growth of tumors by inhibiting DNA synthesis of cancer cells. It has been found recently that many planar polycyclic aromatic hydrocarbons (PAHs) derivatives, previously known as carcinogenic, display anticancer activity through DNA cross-linking. However, the practical use of these PAHs is substantially limited by their low therapeutic efficiency and selectivity toward most tumors.

Alternative Strategy To Explore Missing Proteins with Low Molecular Weight.

Identifying more missing proteins (MPs) is an important mission of C-HPP. With the number of identified MPs being attenuated year by year (2,949 to 2,129 MPs from 2016 to 2019), we have realized that the difficulty of exploring the remaining MPs is a challenge in technique. Herein, we propose a comprehensive strategy to effectively enrich, separate, and identify proteins with low molecular weights, aiming at the discovery of MPs.