Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study.

BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1ß and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.

Knockdown of microplitis mediator odorant receptor involved in the sensitive detection of two chemicals.

Odorant receptors are thought to play critical roles in the perception of chemosensory stimuli by insects. The primary method to address the functions of odorant receptors in insects is to use in vitro binding assays between the receptors and potential chemical stimuli. We injected MmedOrco dsRNA into the abdominal cavity of a braconid wasp, Microplitis mediator, and assayed for expression of this gene 72 h after treatment (RNAi). Quantitative real-time PCR demonstrated that the level of mRNA expression in MmedOrco dsRNA-treated M. mediator was significantly reduced (>90%) when compared with water-treated controls. Furthermore, electroantennogram (EAG) responses of M. mediator to two chemical attractants, nonanal and farnesene, were also reduced significantly (~70%) in RNAi-treated M. mediator when compared to controls. RNAi-treated M. mediator also responded by walking/flying at a lower rate to both chemicals when compared with controls in a Y-tube olfactometer bioassay, which provides direct evidence that MmedOrco plays an important role in perception of nonanal and farnesene in M. mediator.

[Spatiotemporal changes of wetlands in Hangzhou Bay Industrial Belt].

By using RS and GIS techniques, the spatiotemporal changes of wetlands in Hangzhou Bay Industrial Belt, one of the most developed zones in Zhejiang Province, from 1990 to 2005 were studied. There was a frequent conversion between the wetlands and other land use types and between the wetlands themselves, mainly manifested in the conversion between wetland and farmland, and from wetland to construction land and from tidal flat to aquiculture area. The comparative advantage of other land use types and the policy of cultivated land's requisition-compensation balance decided the inherent mechanisms of these spatiotemporal changes. Driven by the aquaculture's comparative advantage to traditional agriculture, large areas of inland farmland and of the tidal flat along the coast of Hangzhou Bay were reclaimed into aquiculture area, and the rapid expansion of construction land, limited land resources, and the implement of cultivated land's requisition-compensation balance policy induced the wetlands being occupied.