Identification of the upstream regulators of KDM5B in gastric cancer.

AIMS: Lysine-specific demethylase 5B (KDM5B) is an epigenetic regulator of chromatin that catalyzes the demethylation of histone 3 lysine 4. It is overexpressed in multiple cancer types and acts as a therapeutic target in cancer therapy. Nevertheless, its upstream regulatory pathway is not completely understood, prompting the search for the underlying biological factors driving KDM5B overexpression. MATERIALS AND METHODS: A comprehensive analysis was performed to examine the association between KDM5B overexpression and copy number variation (CNV), somatic mutation, mRNA expression, miRNA expression, and clinical characters from The Cancer Genome Atlas database. Coexpression and function enrichment analyses were performed with KDM5B-coexpressed genes. The gastric cancer (GC) cell line MKN45 was utilized to verify the regulation of KDM5B using the transcription factor (TF) Yin Yang 1 (YY1) and miR-29a-3p. KEY FINDINGS: KDM5B was overexpressed and associated with poor prognosis in GC. KDM5B upregulation was driven by CNV amplification and DNA hypomethylation rather than by KDM5B mutations. Enrichment analysis revealed that KDM5B-coexpressed genes were primarily related to the transmembrane transport function and the ubiquitin-mediated proteolysis signaling pathway. As a TF, YY1 might bind to the KDM5B promoter region to regulate KDM5B expression. In addition, miR-29a-3p might bind to and negatively regulate KDM5B expression. SIGNIFICANCE: Our results demonstrate that KDM5B expression is regulated via CNV amplification, DNA hypomethylation, and YY1 and miR-29a-3p; KDM5B expression regulation is associated with patient survival and tumor cell proliferation.

SDC: An integrated database for sex differences in cancer.

Sex differences are evident in the incidence and mortality of diverse cancers. With the development of personalized approaches in cancer treatment, the impact of sex differences has not been systematically incorporated into preclinical and clinical cancer research. The molecular mechanisms underlying sex differences in cancer have not been elucidated. Here, we developed the first database of Sex Differences in Cancer (SDC), a web-based public database that integrates resources from multiple databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UCSC Xena, Broad Institute Cancer Cell Line Encyclopedia (CCLE), Genomics of Drug Sensitivity in Cancer (GDSC). SDC contains 27 types of cancers, 6 types of molecular data, more than 10,000 donors, 977 cancer cell lines were used to analyze sex differences among cancers. It provides five main modules: Survival and phenotype, Molecular differences, Signatures and pathways, Therapy response, Download. Users can download the all the visualized results and raw data after analysis. Collectively, SDC is the first integrated database to analyze sex differences in cancer on the web server, which will strengthen our understanding of the role of sex in cancers. It is implemented in Shiny-server and freely available for public use at http://sdc.anticancer.xyz.

Efficient enzymatic synthesis of L-ascorbyl palmitate using Candida antarctica lipase B-embedded metal-organic framework.

The Candida antarctica lipase B (CALB) was embedded in the metal-organic framework, zeolitic imidazolate framework-8 (ZIF-8), and applied in the enzymatic synthesis of L-ascorbic acid palmitate (ASP) for the first time. The obtained CALB@ZIF-8 achieved the enzyme loading of 80 mg g-1 with 11.3 U g-1 (dry weight) unit activity, 59.8% activity recovery, and 92.7% immobilization yield. Under the optimal condition, ASP was synthesized with over 75.9% conversion of L-ascorbic acid in a 10-batch reaction. Continuous synthesis of ASP was subsequently performed in a packed bed bioreactor with an outstanding average space-time yield of 58.1 g L-1  h-1 , which was higher than ever reported continuous ASP biosynthesis reactions.

Schwann cell-seeded scaffold with longitudinally oriented micro-channels for reconstruction of sciatic nerve in rats.

To provide a more permissive environment for axonal regeneration, Schwann cells (SCs) were introduced into a collagen-chitosan scaffold with longitudinally oriented micro-channels (L-CCH). The SC-seeded scaffold was then used for reconstruction of a 15-mm-long sciatic nerve defect in rats. The axonal regeneration and functional recovery were examined by a combination of walking track analysis, electrophysiological assessment, Fluoro-Gold retrograde tracing, as well as morphometric analyses to both regenerated axons and target muscles. The findings showed that SCs adhered and migrated into the L-CCH scaffold and displayed a longitudinal arrangement in vitro. Axonal regeneration as well as functional recovery was in the similar range between SCs-seeded scaffold and autograft groups, which were superior to those in L-CCH scaffold alone group. These indicate that the SCs-seeded L-CCH scaffold, which resembles the microstructure as well as the permissive environment of native peripheral nerves, holds great promise in nerve regeneration therapies.