Multiple species of wild tree peonies gave rise to the ‘king of flowers’, Paeonia suffruticosa Andrews

The origin of cultivated tree peonies, known as the ‘king of flowers'' in China for more than 1000 years, has attracted considerable interest, but remained unsolved. Here, we conducted phylogenetic analyses of explicitly sampled traditional cultivars of tree peonies and all wild species from the shrubby section Moutan of the genus Paeonia based on sequences of 14 fast-evolved chloroplast regions and 25 presumably single-copy nuclear markers identified from RNA-seq data. The phylogeny of the wild species inferred from the nuclear markers was fully resolved and largely congruent with morphology and classification. The incongruence between the nuclear and chloroplast trees suggested that there had been gene flow between the wild species. The comparison of nuclear and chloroplast phylogenies including cultivars showed that the cultivated tree peonies originated from homoploid hybridization among five wild species. Since the origin, thousands of cultivated varieties have spread worldwide, whereas four parental species are currently endangered or on the verge of extinction. The documentation of extensive homoploid hybridization involved in tree peony domestication provides new insights into the mechanisms underlying the origins of garden ornamentals and the way of preserving natural genetic resources through domestication.     

Models and Algorithms for Hub and Spoke Locations for Emergency Service Facilities in Response to Serious Emergency Incidents

This article examines the location-allocation of emergency service facilities as a research subject. The research presents the setup of the single allocation set covering location-allocation models for emergency service facilities under strong time constraints, in view of the shortage of hub & spoke network bypass. The article also presents an extension to the single allocation set covering location-allocation model (SASCP) and the SASCP model with bypass constraints (γ-SASCP) for emergency service facilities under large-scale emergency requirements. For the two models, an improved genetic algorithm was designed and the two models were respectively solved, with the effectiveness of the algorithm verified by a specific example. The impacts of change of parameters such as time discount rate, maximum time constraints, and bypass ratio on the model's results are compared and analyzed, based on solved results by the specific example.     

Adaptive Admixture of HLA Class I Allotypes Enhanced Genetically Determined Strength of Natural Killer Cells in East Asians

Human natural killer (NK) cells are essential for controlling infection, cancer, and fetal development. NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B, and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B, and -C genes, we show that the Chinese Southern Han (CHS) are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the CHS KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C-specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B-specific receptors. In all these characteristics, the CHS represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity, and effector strength, likely augmenting resistance to endemic viral infections.     

灵芝线粒体及其对菌丝生长、主要活性成分影响的分析

线粒体是为细胞提供能量（ATP）的细胞器,携带着自己的DNA——mtDNA,已有多种灵芝属菌株的线粒体基因组相继报道,但对于种内的线粒体基因组的分析较少,对核相同、线粒体不同的菌株间差异的研究也鲜有报道。本研究对两株灵芝线粒体基因组进行组装注释,根据差异片段构建分子标记进行种间分类。结果显示：两株灵芝线粒体基因组大小分别为49 233bp、61 563bp的闭环结构,含有15个常见蛋白编码基因,rRNA大小亚基基因及26个携带氨基酸的tRNA基因,其差异区段主要为内含子序列、大亚基及基因间区。根据cob、cox2基因序列能够进行灵芝种间区分,用于灵芝种间鉴定。本研究还根据灵芝119、灵芝无孢的单核菌株构建同核异质体（TY-119、TY-W）,分析线粒体对菌落形态、菌丝生长速度及多糖、三萜成分的影响,结果显示：同核异质体TY-W与TY-119菌落形态上有一定差异,同核异质体TY-W菌丝生长速度为4.77mm/d,是TY-119菌丝生长速度4.50mm/d的1.06倍,同核异质体TY-119菌丝、子实体阶段多糖含量分别为4.45mg/g、12.14mg/g是TY-W菌丝体多糖含量（3.23mg/g）的1.38倍、子实体多糖含量（10.24mg/g）的1.19倍;同核异质体TY-W菌丝、子实体阶段的三萜含量分别为6.82mg/g、11.45mg/g是同核异质体TY-119菌丝体三萜含量（9.26mg/g）的0.74倍,子实体三萜含量（9.10mg/g）的1.26倍。利用高效液相色谱分析同核异质体中灵芝酸含量显示同核异质体TY-W灵芝酸A、灵芝酸E、灵芝酸F含量分别为3.77μg/mL、14.29μg/mL、12.91μg/mL;是TY-119灵芝酸A含量（2.59μg/mL）的1.46倍、灵芝酸E含量（13.65μg/mL）的1.17倍、灵芝酸F含量（12.72μg/mL）的1.06倍。对同核异质体菌丝、子实体阶段多糖、三萜合成通路关键基因（pgm、ugp、gls、hmgs、hmgr、mvd、fps、sqs）表达量进行检测,显示两菌株间多数基因具有显著性差异。结果表明线粒体的不同会影响灵芝菌落形态、菌丝生长速度及多糖、三萜的含量,有助于我们进一步研究线粒体基因组。     

Aldosterone enhances high phosphate–induced vascular calcification through inhibition of AMPK‐mediated autophagy

It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)‐enhanced vascular calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α‐SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3‐MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate‐activated protein kinase (AMPK) by Compound C attenuated Aldo/MR‐enhanced VC. These results suggested that Aldo facilitates high Pi‐induced VSMC osteogenic phenotypic switch and calcification through MR‐mediated signalling pathways that involve AMPK‐dependent autophagy, which provided new insights into Aldo excess‐associated VC in various settings.     

Antiphospholipid antibody‐activated NETs exacerbate trophoblast and endothelial cell injury in obstetric antiphospholipid syndrome

Despite the widespread use of antiplatelets and anticoagulants, women with antiphospholipid syndrome (APS) may face pregnancy complications associated with placental dysplasia. Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many autoimmune diseases, including vascular APS; however, their role in obstetric APS is unclear. Herein, we investigated the role of NETs by quantifying cell‐free DNA and NET marker levels. Live‐cell imaging was used to visualize NET formation, and MAPK signalling pathway proteins were analysed. Cell migration, invasion and tube formation assays were performed to observe the effects of NETs on trophoblasts and human umbilical vein endothelial cells (HUVECs). The concentrations of cell‐free DNA and NETs in sera of pregnant patients with APS were elevated compared with that of healthy controls (HCs) matched to gestational week. APS neutrophils were predisposed to spontaneous NET release and IgG purified from the patients (APS‐IgG) induced neutrophils from HCs to release NETs. Additionally, APS‐IgG NET induction was abolished with inhibitors of reactive oxygen species, AKT, p38 MAPK and ERK1/2. Moreover, NETs were detrimental to trophoblasts and HUVECs. In summary, APS‐IgG‐induced NET formation deserves further investigation as a potential novel therapeutic target in obstetrical APS.     

Seasonal variation and correlation analysis of vitamin D and parathyroid hormone in Hangzhou,Southeast China

This study aimed to describe the 25‐hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) status of Southeast Chinese individuals influenced by season. The secondary aim was to determine the cutoff for sufficient 25(OH)D in a four‐season region. From January 2011 to June 2014, a total of 17 646 individuals were evaluated in our study. The serum levels of PTH were detected simultaneously in 5579 cases. A total of 25(OH)D and intact PTH were measured by the electrochemiluminescent immunoassay. The distribution of the concentration, prevalence and seasonal variability of 25(OH)D and PTH were studied. The mean 25(OH)D concentration in our study was 43.00(30.40) nmol/L. The prevalence of insufficiency (25(OH)D < 50 nmol/L) was 62.87% and that of deficiency (<30 nmol/L) was 28.54%. Mean serum 25(OH)D levels revealed a limited sinusoidal profile throughout the year and were significantly higher in Autumn. On the other hand, PTH levels showed an opposite response to seasonal effects relative to 25(OH)D. Age, BMI and daylight were not significantly correlated with 25(OH)D and serum PTH reached a plateau at higher values of serum 25(OH)D of 42.86 nmol/L. This study demonstrated that Vitamin D insufficiency is highly prevalent in Southeast China. The concentration of 25(OH)D in the male group was generally higher than that in the female group. Seasonal variation was an important aspect of 25(OH)D and PTH concentration. This study revealed that the optimal serum threshold of 25(OH)D for bone health should be between 40 and 50 nmol/L for Southeast Chinese individuals.