No abstract

Household pesticide exposure during pregnancy has been associated with a more than 2-fold increased risk in infant leukemia, and chlorpyrifos (CPF) is among the most frequently applied insecticides. During early fetal development, liver is a hematopoietic organ with majority of cells being CD34(+) hematopoietic stem cells (CD34(+)HSC). The in utero injury to CD34(+)HSC has been known to underlie the pathogenesis of several blood disorders, often involving rearrangements of the mixed-lineage leukemia (MLL) gene on 11q23. In this study, we evaluated the leukemogenic potential of CPF in human fetal liver-derived CD34(+)HSC. Specifically, exposure to 10 μM CPF led to decrease in viability, inhibition in proliferation and induction of DNA double-strand breaks (DSBs) and occurrence of MLL(+) rearrangements. In particular, we observed CPF-mediated cell cycle disturbance as shown by G0/G1 arrest, in contrast to etoposide (VP-16), an anticancer drug used as a positive control and known to induce G2/M arrest. Further study on mechanisms underlying DNA DSBs and MLL(+) rearrangements revealed that CPF might act as topoisomerase II poison, a mechanism of action similar to VP-16. On the other hand, CPF was also shown to induce early apoptosis through active caspase-3 activation, a pathway known to underlie DNA DSBs and MLL(+) translocations. Our data indicate that in utero injury of CD34(+)HSC by CPF may contribute to the increased risk of infant leukemia. Future work will elucidate the mechanism and the type of CPF-induced MLL(+) translocations in HSC.

Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor a (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5'-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive. The transactivation of ANXA2 promoter by PML/RARα fusion protein was 3.29 ± 0.13 fold higher than that by control pSG5 vector or wild-type RARα. The overexpression of ANXA2 in U937 transfected with full-length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10 transcripts remained constitutive. The tPA-dependent initial rate of plasmin generation (IRPG) in zinc-treated U937/PR9 increased by 2.13-fold, and cell invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or combination of both all remarkably inhibited the IRPG and invasiveness in U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts with all-trans retinoic acid (ATRA) significantly reduced cell surface ANXA2 and S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARα fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.

Weight loss is common in patients with Amyotrophic lateral sclerosis (ALS), and associated with disease progression. Loss of appetite has been shown to be a contributor to weight loss in patients with amyotrophic lateral sclerosis (ALS). However, the reason of loss of appetite is not clear. The Council on Nutrition appetite questionnaire (CNAQ) and the simplified nutritional appetite questionnaire (SNAQ) are short and simple appetite assessment tools, which were using in ALS patients. In our study, the CNAQ and SNAQ were translated into Chinese, and their reliability and validity were tested. The Chinese version of the CNAQ (CNAQ-C) presented more appropriate reliability and validity than the SNAQ. Among the 94 ALS patients, 50 patients (53.2%) had loss of appetite, and we found that anxiety and/or depression contributed to the loss of appetite in the ALS patients. We reconfirmed that loss of appetite was associated with greater weight loss but not with clinical features of ALS. The loss of appetite caused by emotional problems in ALS patients should be taken seriously, and early intervention should be implemented to reduce weight loss.

Visualization is one of the main features of Building Information Modeling (BIM). It has many advantages throughout the lifecycle of a construction project, and it has become a timely research topic in recent years. However, no attempt has been made to give a holistic understanding of the existing BIM-based visualization research status. Thus, this study aims to conduct a scientometric analysis of the existing BIM-based visualization literature and to gain a snapshot of the research status during the period 2010–2019. A total of 255 articles were abstracted from the Scopus database. Then, the VOSviewer program was employed to visualize the research status from the perspectives of scholars, countries/regions, journals, articles, and co-occurring keywords. Results revealed that Wang X. published the greatest number of articles, while Cheng J.C.P. received the greatest average normalized citations. Furthermore, Automation in Construction was identified as the most influential journal and the article “Building information modeling (BIM): trends, benefits, risks, and challenges for the AEC industry” was the most cited paper. Through the keywords co-occurrence analysis, “virtual reality” and “visual programming language” were identified as the emerging themes in this field. The research findings can provide both researchers and practitioners with a better understanding of the status quo and trends of the BIM-based visualization research.