Development of a Machine Learning Model to Distinguish between Ulcerative Colitis and Crohn's Disease Using RNA Sequencing Data.

Crohn's disease (CD) and ulcerative colitis (UC) can be difficult to differentiate. As differential diagnosis is important in establishing a long-term treatment plan for patients, we aimed to develop a machine learning model for the differential diagnosis of the two diseases using RNA sequencing (RNA-seq) data from endoscopic biopsy tissue from patients with inflammatory bowel disease (n = 127; CD, 94; UC, 33). Biopsy samples were taken from inflammatory lesions or normal tissues. The RNA-seq dataset was processed via mapping to the human reference genome (GRCh38) and quantifying the corresponding gene models that comprised 19,596 protein-coding genes. An unsupervised learning model showed distinct clusters of four classes: CD inflammatory, CD normal, UC inflammatory, and UC normal. A supervised learning model based on partial least squares discriminant analysis was able to distinguish inflammatory CD from inflammatory UC after pruning the strong classifiers of normal CD vs. normal UC. The error rate was minimal and affected only two components: 20 and 50 genes for the first and second components, respectively. The corresponding overall error rate was 0.147. RNA-seq analysis of tissue and the two components revealed in this study may be helpful for distinguishing CD from UC.

The effectiveness and safety of electroacupuncture for nonspecific chronic low back pain: A protocol for systematic review and/or meta-analysis.

BACKGROUND: Low back pain (LBP) is a common symptom that affects almost 80% of the global population. LBP manifests as diverse pathologies and has different causes. The focus of this paper is nonspecific chronic low back pain (NSCLBP) wherein the pain lasts for more than 12 weeks, and for which there is no definite cause. Although there are various treatment options for NSCLBP, including medication and exercise, each option has its own limitations. Although electroacupuncture (EA) has been known to have useful analgesic effects on chronic LBP, there is no systematic review (SR) on EA in the literature. Therefore, this study aims to systematically review and validate the effectiveness and safety of EA for NSCLBP. METHODS: We will search for randomized controlled trials on the use of EA for NSCLBP in multiple electronic databases, manual searches, and contacting authors. We will screen and select studies according to the predefined criteria and extract the data needed for this SR. The primary outcome will be the pain index (Visual Analog Scale and Numeric Rating Scale), and the secondary outcomes will be the functional status (Roland-Morris Disability Questionnaire), patient-centered outcomes, and adverse events. We will perform a meta-analysis using Review Manager software (Version 5.3; Copenhagen; The Nordic Cochrane Center, The Cochrane Collaboration, 2014) and assess the risk of bias using Cochrane Collaboration "risk of bias" tools and the quality of evidence using the Grades of Recommendation, Assessment, Development and Evaluation. RESULTS: Our SR will investigate the effectiveness and safety of EA on NSCLBP. CONCLUSION: Our SR will support the published clinical evidence of the usage of EA for NSCLBP to assess the effectiveness and safety of EA. TRIAL REGISTRATION NUMBER: INPLASY; INPLASY2020120039.

A chemical biology route to site-specific authentic protein modifications.

Many essential biological processes are controlled by posttranslational protein modifications. The inability to synthetically attain the diversity enabled by these modifications limits functional studies of many proteins. We designed a three-step approach for installing authentic posttranslational modifications in recombinant proteins. We first use the established O-phosphoserine (Sep) orthogonal translation system to create a Sep-containing recombinant protein. The Sep residue is then dephosphorylated to dehydroalanine (Dha). Last, conjugate addition of alkyl iodides to Dha, promoted by zinc and copper, enables chemoselective carbon-carbon bond formation. To validate our approach, we produced histone H3, ubiquitin, and green fluorescent protein variants with site-specific modifications, including different methylations of H3K79. The methylated histones stimulate transcription through histone acetylation. This approach offers a powerful tool to engineer diverse designer proteins.

Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway.

Upon DNA stimulation, cyclic GMP-AMP synthase (cGAS) synthesizes the second messenger cyclic GMP-AMP (cGAMP) that binds to the STING, triggering antiviral interferon-ß (IFN-ß) production. However, it has remained undetermined how hosts regulate cGAS enzymatic activity after the resolution of DNA immunogen. Here, we show that Akt kinase plays a negative role in cGAS-mediated anti-viral immune response. Akt phosphorylated the S291 or S305 residue of the enzymatic domain of mouse or human cGAS, respectively, and this phosphorylation robustly suppressed its enzymatic activity. Consequently, expression of activated Akt led to the reduction of cGAMP and IFN-ß production and the increase of herpes simplex virus 1 replication, whereas treatment with Akt inhibitor augmented cGAS-mediated IFN-ß production. Furthermore, expression of the phosphorylation-resistant cGAS S291A mutant enhanced IFN-ß production upon DNA stimulation, HSV-1 infection, and vaccinia virus infection. Our study identifies an Akt kinase-mediated checkpoint to fine-tune hosts' immune responses to DNA stimulation.