A longer time to relapse is associated with a larger increase in differences between paired primary and recurrent IDH wild-type glioblastomas at both the transcriptomic and genomic levels.

Glioblastoma (GBM) is the most common malignant brain tumor in adults, which remains incurable and often recurs rapidly after initial therapy. While large efforts have been dedicated to uncover genomic/transcriptomic alternations associated with the recurrence of GBMs, the evolutionary trajectories of matched pairs of primary and recurrent (P-R) GBMs remain largely elusive. It remains challenging to identify genes associated with time to relapse (TTR) and construct a stable and effective prognostic model for predicting TTR of primary GBM patients.

Long-term hematopoietic transfer of the anti-cancer and lifespan-extending capabilities of a genetically engineered blood system by transplantation of bone marrow mononuclear cells.

A causal relationship exists among the aging process, organ decay and disfunction, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed or (K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/EKLF has been generated that possesses extended lifespan and healthy characteristics, including cancer resistance. We show that the healthy longevity characteristics of the (K74R) mice, as exemplified by their higher anti-cancer capability, are likely gender-, age-, and genetic background-independent.

FL-circAS: an integrative resource and analysis for full-length sequences and alternative splicing of circular RNAs with nanopore sequencing.

Circular RNAs (circRNAs) are RNA molecules with a continuous loop structure characterized by back-splice junctions (BSJs). While analyses of short-read RNA sequencing have identified millions of BSJ events, it is inherently challenging to determine exact full-length sequences and alternatively spliced (AS) isoforms of circRNAs. Recent advances in nanopore long-read sequencing with circRNA enrichment bring an unprecedented opportunity for investigating the issues.

The metabolic influence of duodenal mucosal resurfacing for nonalcoholic fatty liver disease.

Background: Nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide with decreased life expectancy. Duodenal mucosal resurfacing (DMR) has been associated with metabolic improvement in glycemic and hepatic parameters of type 2 diabetes, but the metabolic impact of DMR for NAFLD/NASH remains inconclusive. We conducted a meta-analysis to investigate metabolic effects of DMR in patients with NAFLD/NASH.

Detecting intragenic trans-splicing events from non-co-linearly spliced junctions by hybrid sequencing.

Trans-spliced RNAs (ts-RNAs) are a type of non-co-linear (NCL) transcripts that consist of exons in an order topologically inconsistent with the corresponding DNA template. Detecting ts-RNAs is often interfered by experimental artifacts, circular RNAs (circRNAs) and genetic rearrangements. Particularly, intragenic ts-RNAs, which are derived from separate precursor mRNA molecules of the same gene, are often mistaken for circRNAs through analyses of RNA-seq data.

The impact of metformin on survival in diabetes patients with operable colorectal cancer: A nationwide retrospective cohort study.

Objective: To investigate the impact of metformin on survival of diabetic patients following surgery for colorectal cancer (CRC).

Methods: This was a retrospective cohort study. From Taiwan's population-based National Health Insurance Research Database (NHIRD) we identified 12,512 patients with CRC and type II diabetes who underwent curative surgery between 2000 and 2012.

Assessing the impacts of various factors on circular RNA reliability.

Circular RNAs (circRNAs) are non-polyadenylated RNAs with a continuous loop structure characterized by a non-colinear back-splice junction (BSJ). Although millions of circRNA candidates have been identified, it remains a major challenge for determining circRNA reliability because of various types of false positives. Here, we systematically assess the impacts of numerous factors related to circRNA identification, conservation, biogenesis, and function on circRNA reliability by comparisons of circRNA expression from mock and the corresponding colinear/polyadenylated RNA-depleted datasets based on three different RNA treatment approaches.

Trans-genetic effects of circular RNA expression quantitative trait loci and potential causal mechanisms in autism.

Genetic risk variants and transcriptional expression changes in autism spectrum disorder (ASD) were widely investigated, but their causal relationship remains largely unknown. Circular RNAs (circRNAs) are abundant in brain and often serve as upstream regulators of mRNAs. By integrating RNA-sequencing with genotype data from autistic brains, we assessed expression quantitative trait loci of circRNAs (circQTLs) that cis-regulated expression of nearby circRNAs and trans-regulated expression of distant genes (trans-eGenes) simultaneously.

CircMiMi: a stand-alone software for constructing circular RNA-microRNA-mRNA interactions across species.

Background: Circular RNAs (circRNAs) are a class of non-coding RNAs formed by pre-mRNA back-splicing, which are widely expressed in animal/plant cells and often play an important role in regulating microRNA (miRNA) activities. While numerous databases have collected a large amount of predicted circRNA candidates and provided the corresponding circRNA-regulated interactions, a stand-alone package for constructing circRNA-miRNA-mRNA interactions based on user-identified circRNAs across species is lacking.

Results: We present CircMiMi (circRNA-miRNA-mRNA interactions), a modular, Python-based software to identify circRNA-miRNA-mRNA interactions across 18 species (including 16 animals and 2 plants) with the given coordinates of circRNA junctions.

Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells.

The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro.

Anti-gout Medications and Risk of Cardiovascular Disease: A Nested Case-Control Study.

Gout is the leading cause of inflammatory arthritis and is also correlated with multiple comorbidities, including cardiovascular disease (CVD), whose future risk can be lowered by urate-lowering therapy (ULT) in gout patients. It is, however, still not clear whether its effect is associated with the days of usage and the adherence rate of ULT. Data were collected from Taiwan's National Health Insurance Research Database.

Design, synthesis and biological evaluation of glycolamide, glycinamide, and β-amino carbonyl 1,2,4-triazole derivatives as DPP-4 inhibitors.

Through modification of the skeleton of Sitagliptin and Vildagliptin, we successfully synthesized and built-up four series of 1,2,4-triazole derivatives, containing N,O-disubstituted glycolamide, N,N'-disubstituted glycinamide, β-amino ester, and β-amino amide as linkers, for the development of new dipeptidyl peptidase 4 (DPP-4) inhibitors. The synthetic strategy for glycolamides or glycinamides involved convenient two-steps reaction: functionalized transformation of 2-chloro-N-(2,4,5-triflurophenyl)acetamide 9 (hydroxylation or amination) and esterification or amidation of 1,2,4-triazole-3-carboxylic acid. On the other hand, the one-pot synthesis procedure, including substitution and deprotection, was developed for the preparation of β-amino carbonyl 1,2,4-triazoles from (1H-1,2,4-triazol-3-yl)methanol 12 or (1H-1,2,4-triazol-3-yl)methanamine 13 and Boc-(R)-3-amino-4-(2,4,5-trifluoro-phenyl)-butyric acid 14.

The relationships between thyroid-stimulating hormone level and insulin resistance, glucose effectiveness, first- and second-phase insulin secretion in Chinese populations.

Increased insulin resistance (IR); decreased glucose effectiveness (GE); and both first-and second phase of insulin secretion (FPIS, SPIS) have always been important factors for the development of type 2 diabetes. Therefore, in this study, we evaluated the relationships between thyroid-stimulating hormone (TSH) and these 4 factors in adult Chinese. We randomly enrolled 24,407 men and 24,889 women between 30 and 59 years old.

Association Between Use of Anti-gout Preparations and Dementia: Nested Case-Control Nationwide Population-Based Cohort Study.

Gout is the most common form of inflammatory arthritis and was found to be independently associated with incident dementia in the elderly. However, the associations between anti-gout preparations and dementia were not well-studied. Data were collected from Taiwan's National Health Insurance Research Database (NHIRD).

Impact of statin on long-term outcome among patients with end-stage renal disease with acute myocardial infarction (AMI): a nationwide case-control study.

Background: Use of statin has been associated with reduced risk of cardiovascular diseases events and mortality. However, in patients with end-stage renal disease (ESRD), the protective effects of statin are controversial. To evaluate the impact of chronic statin use on clinical outcomes of patients with acute myocardial infarction (AMI) with ESRD.

New methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates as selective COX-2 inhibitors and anti-inflammatory agents: Design, synthesis, biological evaluation, and docking study.

A new method was developed for synthesis of 1,2,4-triazole-3-carboxylates 5a-p and 6 from nitrilimines 3a-p through amination and heterocyclization two-steps reactions. All of 1,2,4-triazole-3-carboxylates 5 and 6 were characterized by spectroscopy technique. Based on the SAR study of anti-inflammation activity, most of these compounds showed potential anti-inflammatory activity on NO inhibition in LPS-induced RAW 264.

Doxorubicin-Gelatin/FeO-Alginate Dual-Layer Magnetic Nanoparticles as Targeted Anticancer Drug Delivery Vehicles.

In this study, magnetic nanoparticles composed of a core (doxorubicin-gelatin) and a shell layer (FeO-alginate) were developed to function as targeted anticancer drug delivery vehicles. The anticancer drug doxorubicin (DOX) was selected as a model drug and embedded in the inner gelatin core to obtain high encapsulation efficiency. The advantage of the outer magnetic layer is that it targets the drug to the tumor tissue and provides controlled drug release.

Electrically modulated varifocal metalens combined with twisted nematic liquid crystals.

Focus-tunable lenses are indispensable to optical systems. This paper proposes an electrically modulated varifocal metalens combined with twisted nematic liquid crystals. In our design, a metalens is employed to focus on different points depending on the polarization state of incident light.

Genome-wide, integrative analysis of circular RNA dysregulation and the corresponding circular RNA-microRNA-mRNA regulatory axes in autism.

Circular RNAs (circRNAs), a class of long noncoding RNAs, are known to be enriched in mammalian neural tissues. Although a wide range of dysregulation of gene expression in autism spectrum disorder (ASD) have been reported, the role of circRNAs in ASD remains largely unknown. Here, we performed genome-wide circRNA expression profiling in postmortem brains from individuals with ASD and controls and identified 60 circRNAs and three coregulated modules that were perturbed in ASD.

A-to-I RNA editing contributes to the persistence of predicted damaging mutations in populations.

Adenosine-to-inosine (A-to-I) RNA editing is a very common co-/posttranscriptional modification that can lead to A-to-G changes at the RNA level and compensate for G-to-A genomic changes to a certain extent. It has been shown that each healthy individual can carry dozens of missense variants predicted to be severely deleterious. Why strongly detrimental variants are preserved in a population and not eliminated by negative natural selection remains mostly unclear.