Nontarget Analysis and Comprehensive Characterization of Iodinated Polyfluoroalkyl Acids in Wastewater and River Water by LC-HRMS with Cascade Precursor-Ion Exclusions and Algorithmic Approach.

Poly- and perfluoroalkyl acids (PFAAs) are a large family of widespread contaminants of worldwide concern and well-known as "forever chemicals". Direct emission of PFAAs from the fluorochemical industry is a crucial source of PFAA pollutants in the environment. This study implemented nontarget analysis and comprehensive characterization for a category of new PFAA contaminants, i.e., iodinated PFAAs (IPFAAs), in fluorochemical industry wastewater and relevant contaminated river water by liquid chromatography-high-resolution mass spectrometry with a cascade precursor ion exclusion (PIE) strategy and in-house developed data extraction and processing algorithms. A total of 26 IPFAAs (including 2 isomers of an IPFAA) were found and identified with tentative molecular structures. Semiquantification of the IPFAAs was implemented, and the total concentrations of IPFAAs were 0.16-285.52 and 0.15-0.17 µg/L in wastewater and river water, respectively. The high concentrations in association with the predicted ecotoxicities and environmental behaviors demonstrate that these IPFAAs are worthy of more concern and further in-depth research. The cascade PIE strategy along with the data extraction and processing algorithms can be extended to nontarget analysis for other pollutants beyond IPFAAs. The nontarget identification and characterization outcomes provide new understanding on the environmental occurrence and pollution status of IPFAAs from a comprehensive perspective.

Identification of cystic fibrosis transmembrane conductance regulator as a prognostic marker for juvenile myelomonocytic leukemia via the whole-genome bisulfite sequencing of monozygotic twins and data mining.

Background: Linked deoxyribonucleic acid (DNA) hypermethylation investigations of promoter methylation levels of candidate genes may help to increase the progressiveness and mortality rates of juvenile myelomonocytic leukemia (JMML), which is a unique myelodysplastic/myeloproliferative neoplasm caused by excessive monocyte and granulocyte proliferation in infancy/early childhood. However, the roles of hypermethylation in this malignant disease are uncertain. Methods: Bone marrow samples from a JMML patient and peripheral blood samples from a healthy monozygotic twin and an unrelated healthy donor were collected with the informed consent of the participant's parents. Whole-genome bisulfite sequencing (WGBS) was then performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to analyze specific differentially methylated region (DMG) related genes. The target genes were screened with Cytoscape and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), which are gene/protein interaction databases. A data mining platform was used to examine the expression level data of the healthy control and JMML patient tissues in Gene Expression Omnibus data sets, and a survival analysis was performed for all the JMML patients. Results: The STRING analysis revealed that the red node [i.e., the cystic fibrosis transmembrane conductance regulator (CFTR)] was the gene of interest. The gene-expression microarray data set analysis suggested that the CFTR expression levels did not differ significantly between the JMML patients and healthy controls (P=0.81). A statistically significant difference was observed in the CFTR promoter methylation level but not in the CFTR gene body methylation level. The overall survival analysis demonstrated that a high level of CFTR expression was associated with a worse survival rate in patients with JMML (P=0.039). Conclusions: CFTR promoter hypermethylation may be a novel biomarker for the diagnosis, monitoring of disease progression, and prognosis of JMML.

Ketone-Olefin Coupling of Aliphatic and Aromatic Carbonyls Catalyzed by Excited-State Acridine Radicals.

Ketone-olefin coupling reactions are common methods for the formation of carbon-carbon bonds. This reaction class typically requires stoichiometric or super stoichiometric quantities of metal reductants, and catalytic variations are limited in application. Photoredox catalysis has offered an alternative method toward ketone-olefin coupling reactions, although most methods are limited in scope to easily reducible aromatic carbonyl compounds. Herein, we describe a mild, metal-free ketone-olefin coupling reaction using an excited-state acridine radical super reductant as a photoredox catalyst. We demonstrate both intramolecular and intermolecular ketone-olefin couplings of aliphatic and aromatic ketones and aldehydes. Mechanistic evidence is also presented supporting an "olefin first" ketone-olefin coupling mechanism.

Bacteriophage therapy for empyema caused by carbapenem-resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a frequent causative agent of post-pneumonectomy empyema-associated broncho-pleural fistula (BPF) and it has a high mortality rate. In recent years, the therapeutic potential of bacteriophage therapy has recognized anew as antimicrobial resistance increases globally. Studies are increasingly reporting the efficacy and safety of bacteriophage therapy for the treatment of multidrug-resistant bacterial infections. However, the clinical efficacy of bacteriophage therapy in empyema has seldom been studied. The current study reports the authors' experience with bacteriophage therapy for a 68-year-old Chinese man who suffered BPF-associated empyema and pneumonia caused by carbapenem-resistant P. aeruginosa. A personalized lytic pathogen-specific two-phage preparation was administered to the patient continuously for 24 days in combination with conventional antibiotics. The treatment was well-tolerated, resulting in clearance of the pathogen and improvement of the clinical outcome. This experience shows that a combined conventional antibiotic treatment with bacteriophage therapy may be effective at alleviating a multidrug-resistant bacterial infection in BPF-associated empyema.