Table1_Text Mining-Based Drug Discovery for Connective Tissue Disease–Associated Pulmonary Arterial Hypertension.DOCX

Background: The current medical treatments for connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) do not show favorable efficiency for all patients, and identification of novel drugs is desired.Methods: Text mining was performed to obtain CTD- and PAH-related gene sets, and the intersection of the two gene sets was analyzed for functional enrichment through DAVID. The protein–protein interaction network of the overlapping genes and the significant gene modules were determined using STRING. The enriched candidate genes were further analyzed by Drug Gene Interaction database to identify drugs with potential therapeutic effects on CTD-PAH.Results: Based on text mining analysis, 179 genes related to CTD and PAH were identified. Through enrichment analysis of the genes, 20 genes representing six pathways were obtained. To further narrow the scope of potential existing drugs, we selected targeted drugs with a Query Score ≥5 and Interaction Score ≥1. Finally, 13 drugs targeting the six genes were selected as candidate drugs, which were divided into four drug–gene interaction types, and 12 of them had initial drug indications approved by the FDA. The potential gene targets of the drugs on this list are IL-6 (one drug) and IL-1β (two drugs), MMP9 (one drug), VEGFA (three drugs), TGFB1 (one drug), and EGFR (five drugs). These drugs might be used to treat CTD-PAH.Conclusion: We identified 13 drugs targeting six genes that may have potential therapeutic effects on CTD-PAH.</p

DataSheet1_Genetic Predispositions Between COVID-19 and Three Cardio-Cerebrovascular Diseases.docx

Aims: This study was aimed to apply a Mendelian randomization design to explore the causal association between coronavirus disease 2019 (COVID-19) and three cardio-cerebrovascular diseases, including atrial fibrillation, ischemic stroke, and coronary artery disease.Methods: Two-sample Mendelian randomization was used to determine the following: 1) the causal effect of COVID-19 on atrial fibrillation (55,114 case participants vs 482,295 control participants), coronary artery disease (34,541 case participants vs 261,984 control participants), and ischemic stroke (34,217 case participants vs 40,611 control participants), which were obtained from the European Bioinformatics Institute, and 2) the causal effect of three cardio-cerebrovascular diseases on COVID-19. The single-nucleotide polymorphisms (SNPs) of COVID-19 were selected from the summary-level genome-wide association study data of COVID-19-hg genome-wide association study (GWAS) meta-analyses (round 5) based on the COVID-19 Host Genetics Initiative for participants with European ancestry. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and Mendelian randomization (MR)-Egger approaches.Results: Genetically predicted hospitalized COVID-19 was suggestively associated with ischemic stroke, with an odds ratio (OR) of 1.049 [95% confidence interval (CI) 1.003–1.098; p = 0.037] in the COVID-19 Host Genetics Initiative GWAS. When excluding the UK Biobank (UKBB) data, our analysis revealed a similar odds ratio of 1.041 (95% CI 1.001–1.082; p = 0.044). Genetically predicted coronary artery disease was associated with critical COVID-19, with an OR of 0.860 (95% CI 0.760–0.973; p = 0.017) in the GWAS meta-analysis and an OR of 0.820 (95% CI 0.722–0.931; p = 0.002) when excluding the UKBB data, separately. Limited evidence of causal associations was observed between critical or hospitalized COVID-19 and other cardio-cerebrovascular diseases included in our study.Conclusion: Our findings provide suggestive evidence about the causal association between hospitalized COVID-19 and an increased risk of ischemic stroke. Besides, other factors potentially contribute to the risk of coronary artery disease in patients with COVID-19, but not genetics.</p

Sulfur-Bridged Co(II)-Thiacalix[4]arene Metal–Organic Framework as an Electrochemical Sensor for the Determination of Toxic Heavy Metals

A novel sulfur-bridged metal–organic framework (MOF) [Co(TIC4R-I)0.25Cl2]·3CH3OH (Co-TIC4R-I) based on thiacalix[4]arene derivatives was successfully obtained using a solvothermal method. Remarkably, adjacent TIC4R-I ligands were linked via Co(II) cations to form a three-dimensional (3D) microporous architecture. Subsequently, Co-TIC4R-I was modified on a glassy carbon electrode (Co-TIC4R-I/GCE) to produce an electrochemical sensor for the detection of heavy-metal ions (HMIs), namely, Cd2+, Pb2+, Cu2+, and Hg2+, in aqueous solutions. It was found that Co-TIC4R-I/GCE exhibited wide linear detection ranges of 0.10–17.00, 0.05–16.00, 0.05–10.00, and 0.80–15.00 μM for Cd2+, Pb2+, Cu2+, and Hg2+, respectively, in addition to low limit of detection (LOD) values of 0.017, 0.008, 0.016, and 0.007 μM. Moreover, the fabricated sensor employed for the simultaneous detection of these metals has achieved LOD values of 0.0067, 0.0027, 0.0064, and 0.0037 μM for Cd2+, Pb2+, Cu2+, and Hg2+, respectively. The sensor also exhibited satisfactory selectivity, reproducibility, and stability. Furthermore, the relative standard deviation (RSD) values of Cd2+, Pb2+, Cu2+, and Hg2+ were 3.29, 3.73, 3.11, and 1.97%, respectively. Moreover, the fabricated sensor could sensitively detect HMIs in various environmental samples. The high performance of the sensor was attributed to its sulfur adsorption sites and abundant phenyl rings. Overall, the sensor described herein provides an efficient method for the determination of extremely low concentrations of HMIs in aqueous samples

Location of three <i>Rhodiola</i> plants and distributions of endophytic fungi in their hosts.

<p>Endophytic fungi were affiliated to at least 11, 13, and 14 orders in <i>R</i>. <i>crenulata</i>, <i>R</i>. <i>angusta</i>, and <i>R</i>. <i>sachalinensis</i>, respectively, which exhibited high diversity.</p

HPLC chromatogram of standard salidroside and <i>p</i>-tyrosol and Rac12 (<i>Lachnum</i> sp.) extract.

<p>HPLC chromatogram of standard salidroside and <i>p</i>-tyrosol and Rac12 (<i>Lachnum</i> sp.) extract.</p

Two Porous Polyoxometalate-Resorcin[4]arene-Based Supramolecular Complexes: Selective Adsorption of Organic Dyes and Electrochemical Properties

Two new inorganic–organic hybrid complexes, namely, {[Co4(L)2(HCOO)2­(OH)2]­[SiO4(W3O9)4]}­·6DMF­·5H2O (1) and {[Zn4(L)2­(HCOO)2­(OH)2]­[SiO4(W3O9)4]}­·6DMF­·5H2O (2), have been solvothermally prepared by using a new methyl imidazole functionalized resorcin[4]­arene (L), polyoxometalate (POM), and metal cation. Isostructural 1 and 2 feature porous supramolecular architectures and represent an unusual example of a successful combination of resorcin[4]­arenes with polyoxometalates. Remarkably, selective adsorptions for organic dyes were studied by using 1 and 2 as adsorbents. Moreover, their electrocatalytic activities for the oxidation of ascorbic acid and reduction of NaBrO3 were also studied

Intracellular Zinc Quantification by Fluorescence Imaging with a FRET System

Fluorescence imaging of cellular metals is widely reported. However, the quantification of intracellular metals with fluorescence imaging is so far not feasible and highly challenging. In this work, a ratiometric probe with two fluorescently labeled complementary DNA strains is designed for intracellular zinc quantification via fluorescence imaging, based on fluorescence resonance energy transfer (FRET) from carbon dots (CDs) to fluorescein (FAM). The donor CDs are modified with a Zn2+ aptamer, whereas the receptor FAM is conjugated with the complementary DNA sequence to ensure selectivity. MCF-7 cells are cultured sequentially with Zn2+ (20, 40, 55, 70, 85, and 100 μmol L–1) and CDs–FAM (100 μg mL–1), which is used for fluorescence imaging (at λex = 405 nm and λem = 440–490 nm for CDs, λem = 500–550 nm for FAM) to provide a relative fluorescence ratio ((F – F0)/F0, F = ICDs/IFAM), followed by quantifying intracellular zinc with ICPMS. A linear correlation is achieved between the relative fluorescence ratio in fluorescence images and the intracellular zinc content derived by ICPMS, which facilitates intracellular zinc quantification via fluorescence imaging. It is especially useful for real-time tracing of intracellular zinc during the cell culturing process or in vivo. The cellular uptake of Zn2+ by MCF-7 cells is further evaluated with this approach by culturing with 100 μmol L–1 of Zn2+ for different times, and a maximum uptake of 60.5 fg per cell is observed at an incubation time of 60 min. This value is further demonstrated well by ICPMS detection

Three new triterpenoid glycosides from <i>Aronia melanocarpa</i> (Michx.) Elliott

Three new triterpenoid glycosides, 2α,3α,23,24-tetrahydroxyurs-12,19- dien-oic acid 28-O-β- D -glucopyranoside (1), 2α,3β,23,24-tetrahydroxyurs-12, 19(29) -dien-28-oic acid 28-O-β- D -glucopyranoside (2), and 2α,3β,23,24-tetrahydroxyurs-12, 18-dien-28-oic acid 28-O-β- D -glucopyranoside (3) were isolated from Aronia melanocarpa (Michx.) Elliott. Their structures were elucidated by extensive spectroscopic methods. All the isolated compounds displayed moderate inhibitory activity against nitric oxide production in macrophages.</p