Seryl tRNA synthetase cooperates with POT1 to regulate telomere length and cellular senescence.

Deregulated telomere length is a causative factor in many physiological and pathological processes, including aging and cancer. Many studies focusing on telomeres have revealed important roles for cooperation between the Shelterin protein complex and telomerase in maintaining telomere length. However, it remains largely unknown whether and how aging-related stresses, such as deregulated protein homeostasis, impact telomere length.

Inhibition of lung cancer growth and metastasis by DHA and its metabolite, RvD1, through miR-138-5p/FOXC1 pathway.

Background: Non small cell lung cancer (NSCLC) is one of the most common cancers in the world. DHA is known to be capable of suppressing NSCLC cell proliferation and metastasis. However, the mechanisms by which DHA exhibits its antitumor effects are unknown.

Down-regulation of Tet2 is associated with Foxp3 TSDR hypermethylation in regulatory T cell of allergic rhinitis.

Aims: Ten-eleven-translocation (Tet) proteins are 5-methylcytosine oxidases and have profound impact on DNA methylation and genes expression. This study aimed to investigate the role of Tet2 and its association with Foxp3 DNA methylation in regulatory T (Treg) cell of allergic rhinitis (AR).

Materials And Methods: CD4CD25Treg cells were sorted from peripheral blood lymphocytes drawn from AR patients and spleen lymphocytes drawn from OVA-exposed mice by flow cytometry.

RHAMM inhibits cell migration via the AKT/GSK3β/Snail axis in luminal A subtype breast cancer.

Breast cancer is one of the most common types of cancer in women. Although the mortality rate of breast cancer has fallen over the past 10 years, effective treatments that reduce the occurrence of breast cancer metastasis remain lacking. In this study, we explored the role of receptor for hyaluronan mediated motility (RHAMM) and the associated signaling pathway in cell migration in luminal A breast cancer.

Targeting Angiogenesis by Blocking the ATM-SerRS-VEGFA Pathway for UV-Induced Skin Photodamage and Melanoma Growth.

Retinoic acid (RA) has been widely used to protect skin from photo damage and skin carcinomas caused by solar ultraviolet (UV) irradiation, yet the mechanism remains elusive. Here, we report that all-trans retinoic acid (RA) can directly induce the expression of a newly identified potent anti-angiogenic factor, seryl tRNA synthetase (SerRS), whose angiostatic role can, however, be inhibited by UV-activated ataxia telangiectasia mutated (ATM) kinase. In both a human epidermal cell line, HaCaT, and a mouse melanoma B16F10 cell line, we found that RA could activate SerRS transcription through binding with the SerRS promoter.

The Effect of on Gut Microbiota, Immune Response and Intestinal Barrier Function During the Development of Necrotic Enteritis in Chickens.

Necrotic enteritis (NE) causes huge economic losses to the poultry industry. Probiotics are used as potential alternatives to antibiotics to prevent NE. It is known that can act as a probiotic that can prevent infection.

Effects of mulberry polyphenols on oxidation stability of sarcoplasmic and myofibrillar proteins in dried minced pork slices during processing and storage.

This experiment was designed to evaluate the influence of mulberry polyphenols (MP) on oxidation stability of sarcoplasmic and myofibrillar proteins in dried minced pork slice during processing and storage. Composition, amino acid side chain modification, average particle size, hydrophobicity and solubility of proteins in the slices were investigated. MP displayed protective effects on oxidation stability of sarcoplasmic and myofibrillar proteins in slices, considering carbonyl formation and transformation from SH group to SS group were remarkably retarded by MP.

Erratum: Author Correction: A novel cancer vaccine with the ability to simultaneously produce anti-PD-1 antibody and GM-CSF in cancer cells and enhance Th1-biased antitumor immunity.

[This corrects the article DOI: 10.1038/sigtrans.2016.

E6-induced selective translation of WNT4 and JIP2 promotes the progression of cervical cancer via a noncanonical WNT signaling pathway.

mRNA translation reprogramming occurs frequently in many pathologies, including cancer and viral infection. It remains largely unknown whether viral-induced alterations in mRNA translation contribute to carcinogenesis. Most cervical cancer is caused by high-risk human papillomavirus infection, resulting in the malignant transformation of normal epithelial cells mainly via viral E6 and E7 oncoproteins.

Break-induced replication plays a prominent role in long-range repeat-mediated deletion.

Repetitive DNA sequences are often associated with chromosomal rearrangements in cancers. Conventionally, single-strand annealing (SSA) is thought to mediate homology-directed repair of double-strand breaks (DSBs) between two repeats, causing repeat-mediated deletion (RMD). In this report, we demonstrate that break-induced replication (BIR) is used predominantly over SSA in mammalian cells for mediating RMD, especially when repeats are far apart.

Assessment of a novel nanostructured flocculant with elevated flocculation and antimicrobial activity.

In this work, a novel process involving the preparation of nanochitosan-grafted flocculants (CPAM-g-NCS) to treat low turbid and salmonella suspensions simultaneously was introduced. Nanotechnology was employed to enhance the adsorption-adhesion and sterilization abilities of dual-functional flocculants. The monomers of chitosan, acrylamide, methacryloyl ethyl trimethyl ammonium chloride, and sodium tripolyphosphate were utilized for flocculants copolymerization.

A novel mutation (c.1010G>T; p.R337L) in TP63 as a cause of split-hand/foot malformation with hypodontia.

Background: Tumor protein p63 (TP63)-related disorders can be divided into at least six categories, including ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC syndrome 3), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome), acro-dermo-ungual-lacrimal-tooth syndrome (ADULT syndrome), limb-mammary syndrome (LMS), Rapp-Hodgkin syndrome (RHS) and split-hand/foot malformation 4 (SHFM4), and are all a result of heterozygous mutations of TP63. The phenotypes of TP63-related disorders broadly involve ectodermal dysplasias, acromelic malformation and orofacial cleft. SHFM and hypodontia are prominent clinical manifestations of TP63-related disorders.

Novel dual inhibitors targeting CDK4 and VEGFR2 synergistically suppressed cancer progression and angiogenesis.

Based on the significantly synergistic effects of CDK4 and VEGFR2 inhibitors on growth of cancer cells, a series of novel multi-kinase inhibitors targeting CDK4 and VEGFR2 were designed, synthesized and evaluated, among which Roxyl-ZV-5J exhibited potent and balanced activities against both CDK4 and VEGFR2 with half-maximal inhibitory concentration at the nanomolar level. It effectively induced breast and cervical cancer cell cycle arrest and cell apoptosis. Roxyl-ZV-5J also inhibited the proliferation, tube formation and VEGFR2 downstream signaling pathways of HUVECs.

Novel cyclin-dependent kinase 9 (CDK9) inhibitor with suppression of cancer stemness activity against non-small-cell lung cancer.

A series of novel, highly potent, selective CDK9 inhibitors with cancer stem cells (CSCs) inhibition activity were designed and synthesized for non-small-cell lung cancer (NSCLC) therapy. Structure-activity relationship analysis based on enzymatic and cellular activities led to the discovery of a promising inhibitor 21e. 21e potently inhibited CDK9 with IC value of 11 nM and suppressed the stemness properties of NSCLC effectively.

Simultaneous and visual detection of infectious bronchitis virus and Newcastle disease virus by multiple LAMP and lateral flow dipstick.

Infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) are both important viruses seriously affecting poultry industry worldwide. In this study, reverse-transcription LAMP (RT-LAMP) was combined with lateral flow dipstick (LFD) forming a novel detection tool which could simultaneously detect IBV and NDV visually. Primers targeted the 5'-untranslated region (5'-UTR) of IBV genome and the conserved region of NDV large polymerase gene (LP).

Pyridine-Functionalized Fullerene Electron Transport Layer for Efficient Planar Perovskite Solar Cells.

In regular perovskite solar cells (PSCs), the commonly used electron transport layer (ETL) is titanium oxide (TiO). Nevertheless, the preparation of a high-quality TiO ETL demands an elevated-temperature sintering procedure, unfavorable for fabrication of PSCs on flexible substrates. Besides, TiO-based devices often suffer from notorious photocurrent hysteresis and serious light soaking instability, limiting their potential commercialization.

CD137 promotes bone metastasis of breast cancer by enhancing the migration and osteoclast differentiation of monocytes/macrophages.

Bone is one of the most common metastatic sites of breast cancer. CD137 (4-1BB), a member of the tumor necrosis factor (TNF) receptor superfamily, is mainly expressed in activated leukocytes. Previous study demonstrates the effect of CD137-CD137L bidirectional signaling pathway on RANKL-mediated osteoclastogenesis.

Enhancement of Histone Deacetylase Inhibitor Sensitivity in Combination with Cyclin-Dependent Kinase Inhibition for the Treatment of Oral Squamous Cell Carcinoma.

Background/aims: Previous research has indicated that the currently available histone deacetylase inhibitors (HDACis) are not effective as monotherapies against oral squamous cell carcinoma (OSCC). However, HDACis act synergistically with other therapeutic agents to exert significant antitumor activities. Thus, a strategy to develop chemotherapeutic agents by combining several active groups based on histone deacetylase (HDAC) into a single molecule as a conjugate that modulates multiple cellular pathways may be useful for the treatment of OSCC.

Atomic-scale structural identification and evolution of Co-W-C ternary SWCNT catalytic nanoparticles: High-resolution STEM imaging on SiO.

Recently, W-based catalysts have provided a promising route to synthesize single-walled carbon nanotubes (SWCNTs) with specific chirality, but the mechanism of the growth selectivity is vaguely understood. We propose a strategy to identify the atomic structure as well as the structure evolution of the Co-W-C ternary SWCNT catalyst. The key is to use a thin SiO film as the catalyst support and observation window.

Telomere Maintenance-Associated PML Is a Potential Specific Therapeutic Target of Human Colorectal Cancer.

Telomere length maintenance is essential for cell proliferation, which is particularly prominent in cancer. We validate that the primary colorectal tumors exhibit heterogeneous telomere lengths but mostly (90%) short telomeres relative to normal tissues. Intriguingly, relatively short telomeres are associated with tumor malignancy as indicated by poorly differentiated state, and these tumors contain more cancer stem-like cells (CSLCs) identified by several commonly used markers CD44, EPHB2 or LGR5.

Structural elucidation of a dimeric impurity in the process development of ceftolozane using LC/HRMS and 2D-NMR.

Ceftolozane is MSD's 5th generation cephalosporin antibiotic with broad-spectrum gram-negative activity. While refining the synthetic route to the drug substance, a dimeric impurity was observed in the final active pharmaceutical ingredient (API) of ceftolozane. Through impurity enrichment and preparative isolation, the structure of the impurity was subsequently established through LC/HRMS, HRMSMS, H/D exchange and 2D-NMR studies.

Exosomal miR-451a Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Targeting LPIN1.

Background/aims: Emerging evidence suggests that exosomal microRNAs (miRNAs) mediate hepatoma progression through the post-translational regulation of their targets. However, characteristically-expressed miRNAs and their functions in the tumor and tumor-associated angiogenesis remain poorly understood.

Methods: miRNA sequencing (HiSeq 2500 SE50) was performed to identify miRNA species that are involved in the hepatocellular carcinoma (HCC) pathogenesis.

ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures.

The structure-specific endonuclease ERCC1/XPF plays an important role in nucleotide excision repair and interstrand cross-link repair. In this study, we identified new functions of ERCC1/XPF in DNA double-strand break (DSB) repair. We found that the conserved function of ERCC1/XPF to remove non-homologous sequences at DSBs is a rate-limiting step for homologous recombination in mammalian cells, and more importantly, we uncovered an indispensable role of ERCC1/XPF in repair of DSBs containing DNA secondary structures, including the structure-prone AT-rich DNA sequences derived from common fragile sites and G-quadruplexes (G4s).

Asparaginyl endopeptidase induces endothelial permeability and tumor metastasis via downregulating zonula occludens protein ZO-1.

Zona occludens-1 (ZO-1) is a key component of tight junctions that govern the function of the endothelial barrier against tumor metastasis. Factors secreted by tumor cells contribute to the maintenance of tumor vascular networks. How tumor cell-derived protein signals regulate ZO-1 expression is unclear.