The role of Pleistocene dispersal in shaping species richness of sky island wintergreens from the Himalaya-Hengduan Mountains.

In addition to topography and climate, biogeographic dispersal has been considered to influence plant diversity in the Himalaya-Hengduan Mountains (HHM), yet, the mode and tempo of sky island dispersal and its influence on species richness has been little explored. Through phylogenetic analysis of Gaultheria ser. Trichophyllae, a sky island alpine clade within the HHM, we test the hypothesis that dispersal has affected current local species richness. We inferred the dynamics of biogeographic dispersal with correlation tests on direction, distance, occurrence time, and regional species richness. We found that G. ser. Trichophyllae originated at the end of the Miocene and mostly dispersed toward higher longitudes (eastward). In particular, shorter intra-regional eastward dispersals and longer inter-regional westward dispersals were most frequently observed. We detected a prevalence of eastward intra-region dispersals in both glacial periods and interglacials. These dispersals may have been facilitated by the reorganization of paleo-drainages and monsoon intensification through time. We suggest that the timing of dispersal corresponding to glacial periods and the prevalence of intra-region dispersal, rather than dispersal frequency, most influenced the pattern of species richness of G. ser. Trichophyllae. This study facilitates a more comprehensive understanding of biodiversity in the sky islands within the HHM.

MicroRNA-124a regulates the differentiation of bone marrow mesenchymal stem cells into neurons.

OBJECTIVE: This study investigated the effects of microRNA-124a on the differentiation of bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanism. METHODS: Flow cytometry was used for isolation and identification of BMSCs. Real-time polymerase chain reaction (RT-PCR) was used to detect gene mRNA expression. Apoptosis was detected using Annexin V-FITC/PI Apoptosis Detection Kit. Cell proliferation ability was tested using Cell Counting Kit-8 (CCK-8). The differentiation of BMSCs into neuron inducers ß-thiol ethanol or baicalin formed the basis of the study. RESULTS: ß-thiol ethanol markedly suppressed the microRNA-124a expression of BMSCs, baicalin markedly induced the microRNA-124a expression of BMSCs and ß-thiol ethanol or baicalin promoted apoptosis and reduced the growth of BMSCs. Only the microRNA-124a inhibitor did not affect apoptosis or the differentiation of BMSCs, and it increased the effects of ß-thiol ethanol or baicalin on the apoptosis of BMSCs. CONCLUSION: ß-thiol ethanol and baicalin treatment could affect microRNA-124a expression in BMSCs. We demonstrated that microRNA-124a promoted the differentiation of BMSCs into neurons.

Discovery of Dipyridamole Analogues with Enhanced Metabolic Stability for the Treatment of Idiopathic Pulmonary Fibrosis.

Dipyridamole, apart from its well-known antiplatelet and phosphodiesterase inhibitory activities, is a promising old drug for the treatment of pulmonary fibrosis. However, dipyridamole shows poor pharmacokinetic properties with a half-life (T1/2) of 7 min in rat liver microsomes (RLM). To improve the metabolic stability of dipyridamole, a series of pyrimidopyrimidine derivatives have been designed with the assistance of molecular docking. Among all the twenty-four synthesized compounds, compound (S)-4h showed outstanding metabolic stability (T1/2 = 67 min) in RLM, with an IC50 of 332 nM against PDE5. Furthermore, some interesting structure-activity relationships (SAR) were explained with the assistance of molecular docking.

MicroRNA let-7f alleviates vascular endothelial cell dysfunction via targeting HMGA2 under oxygen-glucose deprivation and reoxygenation.

Stroke is a fatal disease with high disability and mortality and there is no credible treatment for stroke at present. Studies on stroke are extensively developed to explore the underlying mechanisms of ischemic and reperfusion injuries. Herein, we investigated the functions of microRNA let-7f (also termed let-7f-5p) in vascular endothelial cell dysfunction. The bEnd.3 cells were stimulated with oxygen-glucose deprivation and reoxygenation (OGD/R) to mimic cell injury in vitro. CCK-8 assays, flow cytometry and western blot analyses were conducted to examine the viability and apoptosis of bEnd.3 cells. Reverse transcription quantitative polymerase chain reaction analyses were employed to measure RNA expression. Endothelial cell permeability in vitro assay was employed to assess endothelial permeability of bEnd.3 cells, and expression levels of proteins associated with cell apoptosis or blood-brain barrier (BBB) were detected by western blot analyses. Luciferase reporter assay was conducted to explore the combination between let-7f and HMGA2. We found that OGD/R induced injuries on endothelial cells (bEnd.3) by decreasing cell viability and promoting cell apoptosis. Let-7f exhibited low expression in bEnd.3 cells under OGD/R. Let-7f overexpression increased the viability of bEnd.3 cells and inhibited cell apoptosis. In addition, the endothelial permeability of bEnd.3 cells was increased by OGD/R and reversed by let-7f overexpression. The levels of tight junction proteins (ZO-1 and occludin) were downregulated by OGD/R and then reversed by let-7f overexpression. Mechanistically, HMGA2 is a target gene of let-7f and its expression was negatively regulated by let-7f. Rescue assays revealed that HMGA2 overexpression reversed the effects of let-7f overexpression on cell viability, cell apoptosis, endothelial permeability, and BBB function. In conclusion, let-7f alleviates vascular endothelial cell dysfunction by downregulating HMGA2 expression under OGD/R.

miR-152-3p aggravates vascular endothelial cell dysfunction by targeting DEAD-box helicase 6 (DDX6) under hypoxia.

Stroke is a main cause of disability and death worldwide, and ischemic stroke accounts for most stroke cases. Recently, microRNAs (miRNAs) have been verified to play critical roles in the development of stroke. Herein, we explored effects of miR-152-3p on vascular endothelial cell functions under hypoxia. Human umbilical vein endothelial cells (HUVECs) were treated with hypoxia to mimic cell injury in vitro. Reverse transcription quantitative polymerase chain reaction revealed that miR-152-3p exhibited high expression in HUVECs treated with hypoxia. The inhibition of miR-152-3p reversed hypoxia-induced decrease in cell viability and the increase in angiogenesis, according to the results of cell counting kit-8 assays and tube formation assays. miR-152-3p inhibition reversed the increase in endothelial cell permeability mediated by hypoxia, as shown by endothelial cell permeability in vitro assays. In addition, the increase in protein levels of angiogenetic markers and the decrease in levels of tight junction proteins induced by hypoxia were reversed by miR-152-3p inhibition. Mechanistically, miR-152-3p directly targets 3'-untranslated region of DEAD-box helicase 6 (DDX6), which was confirmed by luciferase reporter assays. DDX6 is lowly expressed in HUVECs under hypoxic condition, and mRNA expression and protein level of DDX6 were upregulated in HUVECs due to miR-152-3p inhibition. Rescue assays showed that DDX6 knockdown reversed effects of miR-152-3p on cell viability, angiogenesis and endothelial permeability. The results demonstrated that miR-152-3p aggravates vascular endothelial cell dysfunction by targeting DDX6 under hypoxia.

Propagation properties of radially and azimuthally polarized chirped Airy-Gaussian vortex beams through slabs of right-handed materials and left-handed materials.

By using Huygens-Fresnel diffraction integral formula and the transfer matrix method, the analytical expression of radially and azimuthally polarized chirped Airy-Gaussian vortex beams through left-handed materials and right-handed materials can be obtained. We study the effects of the chirp factor and the distribution factor on the radially and azimuthally polarized chirped Airy-Gaussian vortex beams in the propagation process, including the light intensity, the phase distribution, the propagation path, the peak intensity, and the radiation force. The focal position of the beams can be adjusted by the chirp parameter.

Key stakeholders' perceptions of the acceptability and usefulness of a tablet-based tool to improve communication and shared decision making in ICUs.

PURPOSE: Although barriers to shared decision making in intensive care units are well documented, there are currently no easily scaled interventions to overcome these problems. We sought to assess stakeholders' perceptions of the acceptability, usefulness, and design suggestions for a tablet-based tool to support communication and shared decision making in ICUs. METHODS: We conducted in-depth semi-structured interviews with 58 key stakeholders (30 surrogates and 28 ICU care providers). Interviews explored stakeholders' perceptions about the acceptability of a tablet-based tool to support communication and shared decision making, including the usefulness of modules focused on orienting families to the ICU, educating them about the surrogate's role, completing a question prompt list, eliciting patient values, educating about treatment options, eliciting perceptions about prognosis, and providing psychosocial support resources. The interviewer also elicited stakeholders' design suggestions for such a tool. We used constant comparative methods to identify key themes that arose during the interviews. RESULTS: Overall, 95% (55/58) of participants perceived the proposed tool to be acceptable, with 98% (57/58) of interviewees finding six or more of the seven content domains acceptable. Stakeholders identified several potential benefits of the tool including that it would help families prepare for the surrogate role and for family meetings as well as give surrogates time and a framework to think about the patient's values and treatment options. Key design suggestions included: conceptualize the tool as a supplement to rather than a substitute for surrogate-clinician communication; make the tool flexible with respect to how, where, and when surrogates can access the tool; incorporate interactive exercises; use video and narration to minimize the cognitive load of the intervention; and build an extremely simple user interface to maximize usefulness for individuals with low computer literacy. CONCLUSION: There is broad support among stakeholders for the use of a tablet-based tool to improve communication and shared decision making in ICUs. Eliciting the perspectives of key stakeholders early in the design process yielded important insights to create a tool tailored to the needs of surrogates and care providers in ICUs.