DataSheet_1_Prognostic value of TIGIT in East Asian patients with solid cancers: A systematic review, meta-analysis and pancancer analysis.pdf

BackgroundT-cell immunoreceptor with Ig and ITIM domains (TIGIT) participates in tumor immune escape by delivering inhibitory signals to T cells. The purpose of this article was to assess the prognostic value of TIGIT and its immunological function in solid cancers.MethodsThree databases were searched for relevant articles. The main endpoints were overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS). Hazard ratios (HR) were pooled by using fixed-effects or random-effects models. Pancancer analysis of TIGIT was performed based on public online databases, mainly The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and UCSC Xena. The possible relationships between TIGIT expression and the tumor microenvironment (TME), infiltration of immune cells, immune-related genes, tumor mutation burden (TMB), and microsatellite instability (MSI) were revealed in this article.ResultsSixteen studies met the inclusion criteria. High expression of TIGIT was associated with worse OS [HR= 1.73, 95% confidence interval (CI) 1.50, 1.99], PFS (HR = 1.53, 95% CI [1.25, 1.88]), RFS (HR = 2.40, 95% CI [1.97, 2.93]), and DFS (HR= 6.57, 95% CI [0.73, 59.16]) in East Asian patients with solid cancers. TIGIT expression was positively correlated with immune infiltration scores and infiltration of CD8 T lymphocytes in all of the cancers included. TIGIT was found to be coexpressed with the genes encoding immunostimulators, immunoinhibitors, chemokines, chemokine receptors, and major histocompatibility complex (MHC), especially in gastroesophageal cancer. TMB and MSI were also associated with TIGIT upregulation in diverse kinds of cancers.ConclusionHigh expression of TIGIT is associated with poorer prognosis in East Asian patients with solid cancers. TIGIT is a novel prognostic biomarker and immunotherapeutic target for various solid cancers because of its activity in cancer immunity and tumorigenesis.</p

Direct Genetic and Enzymatic Evidence for Oxidative Cyclization in Hygromycin B Biosynthesis

Hygromycin B is an aminoglycoside antibiotic with a structurally distinctive orthoester linkage. Despite its long history of use in industry and in the laboratory, its biosynthesis remains poorly understood. We show here, by in-frame gene deletion <i>in vivo</i> and detailed enzyme characterization <i>in vitro</i>, that formation of the unique orthoester moiety is catalyzed by the α-ketoglutarate- and non-heme iron-dependent oxygenase HygX. In addition, we identify HygF as a glycosyltransferase adding UDP-hexose to 2-deoxystreptamine, HygM as a methyltransferase responsible for N-3 methylation, and HygK as an epimerase. These experimental results and bioinformatic analyses allow a detailed pathway for hygromycin B biosynthesis to be proposed, including the key oxidative cyclization reactions

Data_Sheet_1_Cardiovascular adverse events in chronic myeloid leukemia patients treated with nilotinib or imatinib: A systematic review, meta-analysis and integrative bioinformatics analysis.docx

ObjectiveThe aim of this article is to assess the risk and potential mechanisms of cardiovascular adverse events in patients treated with nilotinib or imatinib by conducting a systematic review, meta-analysis and integrative bioinformatics analysis.Materials and methodsThree databases were systematically searched for studies published from inception to May 29, 2022. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to search for modules of genes most associated with cardiotoxicity. Protein-protein interaction (PPI) network analysis was then performed to identify hub genes for the cardiotoxicity of nilotinib. Molecular docking was used to analyze the effects of rosuvastatin and aspirin on these targets.ResultsPatients treated with nilotinib as first-line treatment were associated with a higher risk of CAE (OR = 3.43 [95% CI 2.77–4.25]), CAD (OR = 5.30 [95% CI 3.85–7.29]), ACS (OR 2.7 [95% CI 1.60–4.54]), CVA (OR 5.76 [95% CI 2.84–11.28]), PAOD (OR 5.57 [95% CI 3.26–9.50]) and arrhythmia (OR 2.34 [1.17,4.67]) than those treated with imatinib, while no significant difference was found in the risk of HF (OR 1.40 [95% CI 0.42–4.69]) between the two groups. Patients who were treated with more than 600 mg daily dosage of nilotinib or followed up for more than 5 years had a higher risk of ACS and CVA. IL6, CXCL8, CCL2, SOD2, NFKBIA, and BIRC3 were identified as the top 6 hub genes in the magenta module (human cardiomyocyte samples) and were mainly enriched in the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, lipid and atherosclerosis signaling pathway. TYROBP and CSF1R were identified as hub genes in the turquoise module (liver samples from Mus musculus). GSEA results showed that type II diabetes mellitus, B-cell receptor, apoptosis, insulin, natural killer cell mediated cytotoxicity,mTOR, chemokine, and T-cell receptor signaling pathways were related to the higher risk of atherosclerosis caused by nilotinib. Rosuvastatin can effectively bind to most of the hub targets and proteins enriched in the inflammatory pathways above.ConclusionCML patients who start with nilotinib have a higher risk of CAE than those with imatinib. Atherosclerosis caused by the inflammatory response and glycolipid metabolism disorder is the key mechanism of nilotinib cardiotoxicity. Rosuvastatin may be an effective treatment for the cardiotoxicity of nilotinib.</p

Annealing temperatures.

*<p>ISAG-FAO recommended microsatellite markers for cattle.</p

Experimental design of DNA extraction for PCR and on-chip-electrophoresis.

*<p>ISAG-FAO recommended microsatellite markers for cattle.</p

Effects on the efficiency of real-time PCR of sample amount used for extraction and input template volume.

<p>(A) Second round amplification result (C_T value of <i>ETH225</i>). Six sample amount groups (5 mg, 2 mg, 1 mg, 0.5 mg, 0.2 mg, 0.1 mg) and six template volume groups (different template volumes in first round, but same template volume (2 µl) in second round) of Diao™ enzymatic laundry powder. (B) First round amplification result (C_T value of <i>HAUT27</i>). Six sample amount groups (5 mg, 2 mg, 1 mg, 0.5 mg, 0.2 mg, 0.1 mg) and six template volume groups of Diao™ enzymatic laundry powder. Because of amplification inhibition factors, no C_T value of 5 µl, 2 µl, 1 µl template group and some of 0.5 µl and 0.2 µl template groups were obtained (“undetermined”). Negative controls are not shown in this figure; their C_T values were undetermined too.</p

Comparison of amplification results of DNA extracted from hair shafts using the proposed method and that extracted from liver using commercial Genomic DNA Purification Kit (on-chip-electrophoresis results).

<p>The above panel is <i>INRA035</i> comparison result, sample 6 is amplification result of hair shaft DNA from pure bred Luxi cattle and sample 3 is amplification result of liver DNA from beef cattle; The below panel is <i>CSRM60</i> comparison result, sample 2 is amplification result of hair shaft DNA from pure bred Luxi cattle and sample 11 is amplification result of liver DNA from beef cattle.</p

Experimental design of DNA extraction for real-time PCR

*<p>ISAG-FAO recommended microsatellite markers for cattle. D: Diao™ enzymatic laundry powder. K: Keon™ enzymatic laundry powder. O: OMO™ enzymatic laundry powder. Each sample weight group has 3 extraction reagent groups (8 cattle for each extraction reagent group). For PCR, each sample was set 6 PCR template amount groups in 1^st round.</p

Results after two rounds of Real-time PCR using different enzymatic laundry powder, sample amounts and template volume in the first round PCR.

<p>√ Amplified successfully; × Failed amplification. Neg, reagent blanks. D: Diao™ enzymatic laundry powder. K: Keon™ enzymatic laundry powder. O: OMO™ enzymatic laundry powder.</p

Comparison of different DNA extraction methods.

<p>Comparison of different DNA extraction methods.</p