Photoinduced Decarboxylative Difluoroalkylation and Perfluoroalkylation of α-Fluoroacrylic Acids.

Herein, a novel and practical methodology for the photoinduced decarboxylative difluoroalkylation and perfluoroalkylation of α-fluoroacrylic acids is reported. A wide range of α-fluoroacrylic acids can be used as applicable feedstocks, allowing for rapid access to structurally important difluoroalkylated and polyfluoroalkylated monofluoroalkenes with high Z-stereoselectivity under mild conditions. The protocol demonstrates excellent functional group compatibility and provides a platform for modifying complex biologically active molecules.

Stereoselective Synthesis of Monofluoroalkenylphosphine Oxides via Photoinduced Decarboxylative Coupling of α-Fluoroacrylic Acids with P(O)H Compounds.

Herein, a practical and efficient method for synthesizing monofluoroalkenyl phosphine oxides via photoinduced decarboxylative/dehydrogenative coupling of α-fluoroacrylic acids with phosphine oxides and phosphonates has been developed. Various α-fluoroacrylic acids and P(O)H compounds containing relevant functional groups, including tetrafluorobenzene and pentafluorobenzene, were converted into corresponding products with excellent E-stereoselectivity in satisfactory yields. This method can be extended to achieve the synthesis of monofluoroalkenyl silanes under similar conditions.

Analysis of ancient and modern horse genomes reveals the critical impact of lncRNA-mediated epigenetic regulation on horse domestication.

Background: The domestication of horses has played critical roles in human civilizations. The excavation of ancient horse DNA provides crucial data for studying horse domestication. Studies of horse domestication can shed light on the general mechanisms of animal domestication. Objective: We wish to explore the gene transcription regulation by long noncoding RNAs (lncRNAs) that influence horse domestication. Methods: First, we assembled the ancient DNA sequences of multiple horses at different times and the genomes of horses, donkeys, and Przewalski horses. Second, we extracted sequences of lncRNA genes shared in ancient horses and sequences of lncRNA genes and the promoter regions of domestication-critical genes shared in modern horses, modern donkeys, and Przewalski horses to form two sample groups. Third, we used the LongTarget program to predict potential regulatory interactions between these lncRNAs and these domestication-critical genes and analyzed the differences between the regulation in ancient/modern horses and between horses/donkeys/Przewalski horses. Fourth, we performed functional enrichment analyses of genes that exhibit differences in epigenetic regulation. Results: First, genes associated with neural crest development and domestication syndrome are important targets of lncRNAs. Second, compared with undomesticated Przewalski horses, more lncRNAs participate in the epigenetic regulation in modern horses and donkeys, suggesting that domestication is linked to more epigenetic regulatory changes. Third, lncRNAs' potential target genes in modern horses are mainly involved in two functional areas: 1) the nervous system, behavior, and cognition, and 2) muscle, body size, cardiac function, and metabolism. Conclusion: Domestication is linked to substantial epigenetic regulatory changes. Genes associated with neural crest development and domestication syndrome underwent noticeable lncRNA-mediated epigenetic regulation changes during horse domestication.

Extended transcriptome analysis reveals genome-wide lncRNA-mediated epigenetic dysregulation in colorectal cancer.

It is estimated that the rate of epigenetic changes may be orders of magnitude higher than that of genetic changes and that purely epigenetic mechanisms may explain why cancers arise with few or no recurrent mutations. However, supporting evidence remains limited, partly due to the cost of experimentally studying genome-wide epigenetic dysregulation. Since genome modification enzymes are recruited by long noncoding RNAs (lncRNAs) to specific genomic sites, analyzing differentially expressed genes and differentially methylated regions (DMRs) at the DNA binding sites of differentially expressed lncRNAs is important for uncovering epigenetic dysregulation. We performed RNA-seq and MeDIP-seq on a set of colorectal cancer (CRC) and normal colon samples and developed an analysis pipeline for combined analyses of gene expression, DNA methylation, and lncRNA/DNA binding. The genes identified in our data and important for CRC agree with widely reported findings. We found that aberrantly transcribed noncoding transcripts may epigenetically dysregulate genes, that correlated gene expression is significantly determined by epigenetic dysregulation, that differentially expressed noncoding transcripts and their epigenetic targets form distinct modules in different cancer cells, and that many hub lncRNAs in these modules are primate-specific. These results suggest that lncRNA-mediated epigenetic dysregulation greatly determines aberrant gene expression and that epigenetic dysregulation is highly species-specific. The analysis pipeline can effectively unveil cancer- and cell-specific modules of epigenetic dysregulation, and such modules may provide novel clues for identifying diagnostic, therapeutic, and prognostic targets for epigenetic dysregulation.

Shortened telomere length in peripheral blood leukocytes of patients with lung cancer, chronic obstructive pulmonary disease in a high indoor air pollution region in China.

Lung cancer and chronic obstructive pulmonary disease (COPD) are closely linked diseases. In Xuanwei, China, the extremely high incidence and mortality rates of lung cancer and COPD are associated with exposure to household smoky coal burning. Previous studies found that telomere length was related to lung disease. The objective of this study is to investigate the relationship of peripheral blood leukocyte telomere length to both lung cancer and COPD, as well as indoor coal smoke exposure in Xuanwei. We measured telomere length using quantitative polymerase chain reaction (qPCR) in peripheral blood leukocytes of 216 lung cancer patients, 296 COPD patients, and 426 healthy controls from Xuanwei. The telomere length ratios (mean ± SD) in patients with lung cancer (0.76 ± 0.35) and COPD (0.81 ± 0.35) were significantly shorter than in that of controls (0.95 ± 0.39). Individuals with the shortest tertile telomere length had 3.90- and 4.54-fold increased risks of lung cancer and COPD, respectively, compared with individuals with the longest tertile telomere length. No correlation was found between telomere length and pack-years of smoking. In healthy subjects, coal smoke exposure level affected telomere length. Lung function was positively and negatively associated with telomere length and environmental exposure, respectively, when combination the control and COPD groups. The result suggests that shortened telomere length in peripheral blood leukocytes was associated with lung cancer and COPD and might be affected by coal smoke exposure level in Xuanwei. Whether variation in telomere length caused by environmental exposure has a role in lung cancer and COPD development and exacerbation needs further research.

An Overlooked Paleotetraploidization in Cucurbitaceae.

Cucurbitaceae plants are of considerable biological and economic importance, and genomes of cucumber, watermelon, and melon have been sequenced. However, a comparative genomics exploration of their genome structures and evolution has not been available. Here, we aimed at performing a hierarchical inference of genomic homology resulted from recursive paleopolyploidizations. Unexpectedly, we found that, shortly after a core-eudicot-common hexaploidy, a cucurbit-common tetraploidization (CCT) occurred, overlooked by previous reports. Moreover, we characterized gene loss (and retention) after these respective events, which were significantly unbalanced between inferred subgenomes, and between plants after their split. The inference of a dominant subgenome and a sensitive one suggested an allotetraploid nature of the CCT. Besides, we found divergent evolutionary rates among cucurbits, and after doing rate correction, we dated the CCT to be 90-102 Ma, likely common to all Cucurbitaceae plants, showing its important role in the establishment of the plant family.

[Therapeutic effects of umbilical cord mesenchymal stem cells transplantation on systemic lupus erythematosus].

OBJECTIVE: To observe the efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) transplantation for the patients with refractory systemic lupus erythematosus (SLE). METHODS: Thirty seven patients with SLE were enrolled in this study, and divided into conventional treatment group (control group, n = 20) and UC-MSCS adjuvant treatment group (treatment group, n= 17). All the patients in both two groups were treated with glucocorticoids and cyclophosphamide (CTX). In the UC-MSCs group, each patient additionally received the transplantation of 3 x 10(7) UC-MSCs infusion intravenously. The clinical manifestations and laboratory parameters of each patient were observed before the treatments and 2 weeks, 1 month, 2 months, 3 months, months,9 months and 12 months after the treatments. RESULTS: All the 37 patients were observed for 12 months. 24 h urinary protein excretion (U-Pro), anti nuclear antibody (ANA), erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), systemic lupus erythematosus disease activity index (SLEDAI) of these two groups decreased significantly (P < 0.05). serum albumin (ALB), C3, and C4 of two groups were higher after the treatments (P < 0.05). ALB and C3 in treatment group exceeded the control group (P < 0.05). The positive rates of Anti-dsDNA in control and treatment group were 40% and 10% respectively, while the recurrence rates were 50% and 20% respectively, these difference between the two groups were statistically significant (P < 0.05). There were no transplantation related complications observed. CONCLUSION: UC-MSCs transplantation could be effective and safe for refractory SLE on basis of glucocorticoid and cyclophosphamide therapy.