The PERK Branch of the Unfolded Protein Response Safeguards Protein Homeostasis and Mesendoderm Specification of Human Pluripotent Stem Cells.

Cardiac development involves large-scale rearrangements of the proteome. How the developing cardiac cells maintain the integrity of the proteome during the rapid lineage transition remains unclear. Here it is shown that proteotoxic stress visualized by the misfolded and/or aggregated proteins appears during early cardiac differentiation of human pluripotent stem cells and is resolved by activation of the PERK branch of unfolded protein response (UPR).

Transcriptomics and co-expression network analysis revealing candidate genes for the laccase activity of Trametes gibbosa.

Background: Trametes gibbosa, which is a white-rot fungus of the Polyporaceae family found in the cold temperate zone, causes spongy white rot on wood. Laccase can oxidize benzene homologs and is one of the important oxidases for white rot fungi to degrade wood. However, the pathway of laccase synthesis in white rot fungi is unknown.

Expression and clinical significance of lncRNA-SChLAP1 in breast cancer.

Purpose: The purpose of this study was to investigate the expression of long non-coding RNA (lncRNA)-SChLAP1 in breast cancer (BCa) tissues and its clinical significance in the progression of this cancer.

Methods: 100 pairs of surgically resected BCa tissue samples and normal breast tissues were collected from BCa patients, and SChLAP1 expression in above tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, the receiver operating curve (ROC) was plotted to analyze the efficacy of SChLAP1 in the diagnosis of BCa.

Targeted RNA N -Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells.

Deficiency of the N -methyladenosine (m A) methyltransferase complex results in global reduction of m A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m A methylation affects cell fate decisions due to the inability to modulate individual m A modification in ESCs with precise temporal control. Here, a targeted RNA m A erasure (TRME) system is developed to achieve site-specific demethylation of RNAs in human ESCs (hESCs).

miR‑589‑3p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R.

The long non‑coding (lnc)RNA named tissue differentiation inducing non‑protein coding RNA (TINCR) is a tumor marker that has not been studied in breast cancer. The present study aimed to investigate the TINCR‑targeting micro (mi)RNAs and the regulatory mechanisms of TINCR in breast cancer. Following prediction by TargetScan and confirmation by dual‑luciferase reporter assay, TINCR was demonstrated to be a target gene for miR‑589‑3p.

Application of transoral endoscopic parathyroidectomy via vestibular approach, endoscopic parathyroidectomy via areola approach for parathyroid adenoma.

Background: Transoral endoscopic parathyroidectomy via vestibular approach (TOEPVA) and total endoscopic parathyroidectomy via areola approach (EPA) are commonly used endoscopic parathyroidectomy approaches. This study compares effectiveness of these approaches with conventional open parathyroidectomy (COP) in relation to safety, associated trauma, and feasibility in the treatment of parathyroid adenoma (PTA).

Methods: We examined patients who had undergone TOEPVA (n = 15), EPA (n = 14), and COP (n = 30).

PCGF6 regulates stem cell pluripotency as a transcription activator via super-enhancer dependent chromatin interactions.

Polycomb group (PcG) ring finger protein 6 (PCGF6), though known as a member of the transcription-repressing complexes, PcG, also has activation function in regulating pluripotency gene expression. However, the mechanism underlying the activation function of PCGF6 is poorly understood. Here, we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4.

Long non-coding RNA ANRIL promotes carcinogenesis via sponging miR-199a in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a complex breast cancer subtype characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2). Long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) has been verified as oncogenic molecular in series of tumors, however, the role of ANRIL in TNBC carcinogenesis is still unclear. The purpose of present study is to investigate the expression and in-depth regulation of ANRIL on TNBC tumorigenesis.

Synthesis of Spiroligomer-Containing Macrocycles.

We demonstrate the synthesis and characterization of the solution conformations of a collection of functionalized spiroligomer-based macrocycles. These macrocycles contain 14 independently controllable stereocenters and four independently controllable functional groups on a highly preorganized scaffold. These molecules are being developed to display complex, preorganized surfaces for binding proteins and to create enzyme-like active sites.

Proteasome inhibitors with pyrazole scaffolds from structure-based virtual screening.

We performed a virtual screen of ∼340 000 small molecules against the active site of proteasomes followed by in vitro assays and subsequent optimization, yielding a proteasome inhibitor with pyrazole scaffold. The pyrazole-scaffold compound displayed excellent metabolic stability and was highly effective in suppressing solid tumor growth in vivo. Furthermore, the effectiveness of this compound was not negatively impacted by resistance to bortezomib or carfilzomib.

Knockdown of CETN1 inhibits breast cancer cells proliferation.

Purpose: Breast cancer is a multifactorial disease and identification of the genes and proteins regulating breast carcinogenesis is critical in exploring novel targeted therapies. The aim of this study was to investigate the role CETN1 in breast cancer growth and metastasis.

Methods: CETN1 expression levels were measured in breast tissue samples by immunohistochemistry (IHC).

Spiroligozymes for transesterifications: design and relationship of structure to activity.

Transesterification catalysts based on stereochemically defined, modular, functionalized ladder-molecules (named spiroligozymes) were designed, using the "inside-out" design strategy, and mutated synthetically to improve catalysis. A series of stereochemically and regiochemically diverse bifunctional spiroligozymes were first synthesized to identify the best arrangement of a pyridine as a general base catalyst and an alcohol nucleophile to accelerate attack on vinyl trifluoroacetate as an electrophile. The best bifunctional spiroligozyme reacted with vinyl trifluoroacetate to form an acyl-spiroligozyme conjugate 2.

Hydrophobic substituent effects on proline catalysis of aldol reactions in water.

Derivatives of 4-hydroxyproline with a series of hydrophobic groups in well-defined orientations have been tested as catalysts for the aldol reactions. All of the modified proline catalysts carry out the intermolecular aldol reaction in water and provide high diastereoselectivity and enantioselectivity. Modified prolines with aromatic groups syn to the carboxylic acid are better catalysts than those with small hydrophobic groups (1a is 43.