Coping with alpine habitats: genomic insights into the adaptation strategies of Triplostegia glandulifera (Caprifoliaceae).

How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera. A series of genes putatively associated with alpine adaptation (e.g. CBFs, ERF-VIIs, and RAD51C) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica. Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica, indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNLs, prRLPs, and XII RLKs), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1, DMC1, and MSH3) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants.

Spatial heterogeneity of neo- and paleo-endemism for plants in Madagascar.

Madagascar is a biogeographically unique island with a remarkably high level of endemism. However, endemic taxa in Madagascar are massively threatened due to unprecedented pressures from anthropogenic habitat modification and climate change. A comprehensive phylogeny-based biodiversity evaluation of the island remains lacking. Here, we identify hotspots of taxonomic and phylogenetic plant diversity and neo- and paleo-endemism by generating a novel dated tree of life for the island. The tree is based on unprecedented sampling of 3,950 species (33% of the total known species) and 1,621 genera (93% of the total known genera and 69% of endemic genera) of Malagasy vascular plants. We find that island-endemic genera are concentrated in multiple lineages combining high taxonomic and phylogenetic diversity. Integrating phylogenetic and geographic distribution data, our results reveal that taxon richness and endemism are concentrated in the northern, eastern, and southeastern humid forests. Paleo-endemism centers are concentrated in humid eastern and central regions, whereas neo-endemism centers are concentrated in the dry and spiny forests in western and southern Madagascar. Our statistical analysis of endemic genera in each vegetation region supports a higher proportion of ancient endemic genera in the east but a higher proportion of recent endemic genera in the south and west. Overlaying centers of phylogenetic endemism with protected areas, we identify conservation gaps concentrated in western and southern Madagascar. These gaps should be incorporated into conservation strategies to aid the protection of multiple facets of biodiversity and their benefits to the Malagasy people.

The Sino-Himalayan flora evolved from lowland biomes dominated by tropical floristic elements.

BACKGROUND: The Sino-Himalayan flora harbors highly diverse high-elevation biotas, but our understanding of its evolutionary history in temporal and spatial dimensions is limited. In this study, we integrated a dated phylogenetic tree with comprehensive species distribution data to investigate changes over time and space in floristic elements, including the tropical, Tethys, northern temperate, and East Asian floristic elements, across the entire Sino-Himalaya and its three floristic regions: the Yunnan Plateau, Hengduan Mountains, and East Himalaya regions. RESULTS: Our results revealed that the Sino-Himalayan flora developed from lowland biomes and was predominantly characterized by tropical floristic elements before the collision between the Indian subcontinent and Eurasia during the Early Cenozoic. Subsequently, from the Late Eocene onwards, the uplifts of the Himalaya and Hengduan Mountains transformed the Sino-Himalayan region into a wet and cold plateau, on which harsh and diverse ecological conditions forced the rapid evolution of local angiosperms, giving birth to characteristic taxa adapted to the high altitudes and cold habitat. The percentage of temperate floristic elements increased and exceeded that of tropical floristic elements by the Late Miocene. CONCLUSIONS: The Sino-Himalayan flora underwent four significant formation periods and experienced a considerable increase in endemic genera and species in the Miocene, which remain crucial to the present-day patterns of plant diversity. Our findings support the view that the Sino-Himalayan flora is relatively young but has ancient origins. The three major shifts in the divergence of genera and species during the four formation periods were primarily influenced by the uplifts of the Himalaya and Hengduan Mountains and the onset and intensification of the Asian monsoon system. Additionally, the temporal patterns of floristic elements differed among the three floristic regions of the Sino-Himalaya, indicating that the uplift of the Himalaya and surrounding areas was asynchronous. Compared to the Yunnan Plateau region, the East Himalaya and Hengduan Mountains experienced more recent and drastic uplifts, resulting in highly intricate topography with diverse habitats that promoted the rapid radiation of endemic genera and species in these regions.

Exploratory study on tissue ablation with cryoelectrolysis.

This is an exploratory study on the effect of electrolysis, delivered during the thawing stage of a cryoablation protocol, on tissue ablation. This treatment protocol, that combines freezing and electrolysis, is named "cryoelectrolysis". In cryoelectrolysis the cryoablation probe is also used as the electrolysis delivering electrode. The study was performed on the liver of Landrace pigs and the tissues were examined 24 hours after treatment (two pigs) and 48 hours after treatment (one pig). The cryoelectrolysis device and different cryoelectrolysis ablation configurations tested are described. This exploratory, non-statistical study shows that the addition of electrolysis expands the ablated area in comparison to cryoablation alone and that there is a substantial difference between the histological appearance of tissue treated by cryoablation alone, tissue treated by cryoablation and electrolysis at the anode and tissue treated by cryoablation and electrolysis at the cathode.

A chromosome-level genome of Syringa oblata provides new insights into chromosome formation in Oleaceae and evolutionary history of lilacs.

Lilacs (Syringa L.), a group of well-known ornamental and aromatic woody plants, have long been used for gardening, essential oils and medicine purposes in East Asia and Europe. The lack of knowledge about the complete genome of Syringa not only hampers effort to better understand its evolutionary history, but also prevents genome-based functional gene mining that can help in the variety improvement and medicine development. Here, a chromosome-level genome of Syringa oblata is presented, which has a size of 1.12 Gb including 53 944 protein coding genes. Synteny analysis revealed that a recent duplication event and parallel evolution of two subgenomes formed the current karyotype. Evolutionary analysis, transcriptomics and metabolic profiling showed that segment and tandem duplications contributed to scent formation in the woody aromatic species. Moreover, phylogenetic analysis indicated that S. oblata shared a common ancestor with Osmanthus fragrans and Olea europaea approximately 27.61 million years ago (Mya). Biogeographic reconstruction based on a resequenced data set of 26 species suggested that Syringa originated in the northern part of East Asia during the Miocene (approximately 14.73 Mya) and that the five Syringa groups initially formed before the Late Miocene (approximately 9.97 Mya). Furthermore, multidirectional dispersals accompanied by gene introgression among Syringa species from Northern China during the Miocene were detected by biogeographic reconstruction. Taken together, the results showed that complex gene introgression, which occurred during speciation history, greatly contributed to Syringa diversity.

Distribution patterns and industry planning of commonly used traditional Chinese medicinal plants in China.

Medicinal plants are the primary material basis for disease prevention and treatment in traditional Chinese medicine (TCM). The conservation and sustainable utilization of these medicinal plants is critical for the development of the TCM industry. However, wild medicinal plant resources have sharply declined in recent decades. To ameliorate the shortage of medicinal plant resources, it is essential to explore the development potential of the TCM industry in different geographical regions. For this purpose, we examined the spatial distribution of commonly used medicinal plants in China, the number of Chinese medicinal material markets, and the number of TCM decoction piece enterprises. Specifically, multispecies superimposition analysis and Thiessen polygons were used to reveal the optimal range for planting bulk medicinal plants and the ideal regions for building Chinese medicinal material markets, respectively. Furthermore, we quantitatively analyzed mismatches between the spatial distribution of commonly used medicinal plant richness, Chinese medicinal material markets, and TCM decoction piece enterprises. We found that the areas suitable for growing commonly used medicinal plants in China were mainly distributed in Hengduan Mountain, Nanling Mountain, Wuling Mountain, and Daba Mountain areas. The Thiessen polygon network based on Chinese medicinal material market localities showed there are currently fewer markets in southwestern, northwestern, and northeastern China than in central and southern China. TCM decoction piece enterprises are concentrated in a few provinces, such as Hebei and Jiangxi. We found that the distribution of commonly used medicinal plants, Chinese medicinal material markets and TCM decoction piece enterprises are mismatched in Henan, Shaanxi, Hunan, Hubei, Zhejiang, Fujian, Chongqing, and Xizang. We recommend strengthening development of the TCM industry in Henan, Hunan, Zhejiang, Shaanxi, Hubei, Chongqing, Fujian, and Xizang; building more Chinese medicinal material markets in southwestern, northwestern, and northeastern China; and establishing medicinal plant nurseries in resource-rich provinces to better protect and domesticate local medicinal plants.

A randomized non-inferiority study of low-dose and standard-dose ticagrelor after intervention for acute coronary syndrome: study protocol for the TIGER STUDY.

BACKGROUND: Current guidelines recommend that patients with acute coronary syndrome (ACS) who have successfully undergone percutaneous coronary intervention (PCI) should continue to use dual antiplatelet therapy (DAPT) for 12 months. The long-term use of standard-dose dual antiplatelet therapy will increase the risk of bleeding. An optimized antiplatelet strategy that can prevent ischemic events and reduce the risk of bleeding remains to be explored. METHODS: The study is a prospective, multicenter, randomized, open-label, controlled study involving 2090 patients from six clinical centers in China. Through the interactive web response system (IWRS), ACS patients undergoing successful PCI will be randomly divided into the low-dose ticagrelor group or the normal-dose ticagrelor group, after taking 100 mg aspirin and 90 mg ticagrelor bid for 1 week. The primary endpoint is a composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, repeat revascularization, and stroke. The secondary endpoints are bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria, cardiovascular death, acute myocardium infarction, and coronary revascularization at 1 year. DISCUSSION: Recent studies have confirmed that 90 mg ticagrelor alone can safely and effectively reduce bleeding without increasing ischemic events of patients with ACS after PCI. Compared with standard-dose DAPT, whether low-dose ticagrelor combined with aspirin can ensure the anti-ischemic effect while reducing the bleeding risk remains unclear in Chinese patients. The TIGER study will be the first large-scale, multicenter study to compare the efficacy and safety of low-dose and standard-dose ticagrelor combined with aspirin in ACS patients 1 week after successful PCI. TRIAL REGISTRATION: Clinicaltrials.gov NCT04255602. Registered on 5 February 2020.

Spatial phylogenetics of the Chinese angiosperm flora provides insights into endemism and conservation.

The flora of China is well known for its high diversity and endemism. Identifying centers of endemism and designating conservation priorities are essential goals for biodiversity studies. However, there is no comprehensive study from a rigorous phylogenetic perspective to understand patterns of diversity and endemism and to guide biodiversity conservation in China. We conducted a spatial phylogenetic analysis of the Chinese angiosperm flora at the generic level to identify centers of neo- and paleo-endemism. Our results indicate that: (i) the majority of grid cells in China with significantly high phylogenetic endemism (PE) were located in the mountainous regions; (ii) four of the nine centers of endemism recognized, located in northern and western China, were recognized for the first time; (iii) arid and semiarid regions in Northwest China were commonly linked to significant PE, consistent with other spatial phylogenetic studies worldwide; and (iv) six high-priority conservation gaps were detected by overlaying the boundaries of China's nature reserves on all significant PE cells. Overall, we conclude that the mountains of southern and northern China contain both paleo-endemics (ancient relictual lineages) and neo-endemics (recently diverged lineages). The areas we highlight as conservation priorities are important for broad-scale planning, especially in the context of evolutionary history preservation.

Predicting potential medicinal plants with phylogenetic topology: Inspiration from the research of traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants are a dominant source of pharmacological drugs for the treatment and cure of different disorders and diseases. However, selecting the most biologically active plant species for further screening is still challenging. Phylogeny has strong explanatory powers and provides predictive perspectives that are not available in traditional plant classifications. China, which is endowed with a diverse set of therapeutic cures from Mother Nature, represents an ideal environment for the phylogenetic analysis of potential medicinal plants. MATERIALS AND METHODS: Herein, we prepared a database of 7,451 traditional Chinese medicinal (TCM) plants, including species with therapeutic effects grouped in 14 categories. To limit our exploration of novel therapeutic species, we plotted the medicinal effects on the phylogenetic tree of almost 30,000 species of China to find hot nodes of therapeutic effects. We used the net relatedness index (NRI) and the nearest taxon index (NTI) to identify clustering and overdispersion of the phylogenetic distribution of TCM plants. RESULTS: The NRI and NTI analyses highlighted 3,392 hot node species with single therapeutic effects within 507 genera and 89 families on the phylogenetic tree and about 70% of the 14 medicinal categories clusters identified. The general pattern of the hot nodes on the phylogenetic tree indicates that basal angiosperms and basal eudicots radiated for therapeutic effects. CONCLUSIONS: Our study may provide a more targeted way to discover phylogeny-guided drugs in the early screening stage, which may lead to a higher discovery efficiency of new drugs with meaningful biological activities. Phylogenetic studies of plants that are richer in bioactive compounds can set the ground for the identification and discovery of alternative drugs.

Characterization of the complete chloroplast genome of Pterocarya macroptera var. delavayi (Juglandaceae).

In this study, the complete chloroplast genome sequence of Pterocarya macroptera var. delavayi was reported and characterized. The chloroplast genome is 160,168 bp in length, and consists the typical quadripartite structure, a pair of inverted repeats (IRs, 26,007 bp) separated by a large single-copy region (89,701 bp) and a small single-copy region (18,453 bp). A total of 136 unique genes were predicted, including 88 protein-coding genes, 40 tRNA genes, and 8 rRNA genes. The GC content of the chloroplast genome is 36.2%. Phylogenetic analysis confirmed the close relationship between Pterocarya and Juglans.

Prognostic value of asymmetric dimethylarginine in patients with coronary artery disease: A meta-analysis.

BACKGROUND: Studies regarding the predictive utility of the blood level of asymmetric dimethylarginine (ADMA) in patients with coronary artery disease (CAD) have yielded the conflicting findings. This meta-analysis sought to evaluate the prognostic value of blood ADMA level in CAD patients. METHODS: Potentially relevant studies were identified by searching PubMed and Embase database until August 12, 2020. Cohort studies evaluating the association of blood ADMA level with all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACEs) were included. A random effect model was applied to pool the multivariable-adjusted risk ratio (RR) and 95% confidence intervals (CI) for the highest versus lowest ADMA level. RESULTS: Data were retrieved from 11 studies enrolling a total of 9496 CAD patients. When compared the highest to the lowest ADMA level, the pooled RR was 2.10 (95% CI 1.46-3.02) for all-cause mortality, 2.49 (95% CI 1.34-4.65) for cardiovascular mortality, and 1.71 (95% CI 1.27-2.32) for MACEs, respectively. However, subgroup analysis showed that there were no significant association between elevated ADMA level and all-cause mortality in acute coronary syndrome (RR 2.11; 95% CI 0.93-4.78) and follow up ≤ 1 year (RR 2.15; 95% CI 0.56-8.25) subgroup. CONCLUSIONS: Elevated blood ADMA level is possibly an independent predictor of all-cause mortality, cardiovascular mortality, and MACEs in CAD patients. Measurement of blood level of ADMA may improve risk classification of CAD. However, these findings should be interpreted with caution because of the limited number of studies included.

Pternopetalum paucifoliolatum (Apiaceae), a new Critically Endangered species from Sichuan, China.

Pternopetalum paucifoliolatum, a new species from Sixigou Scenic Area, Emeishan City, Sichuan Province, is proposed and described. Diagnostic morphological characters, full description, detailed illustrations, and a distribution map are provided. The new species is similar to P. porphyronotum in possessing the 1-pinnate leaves and the abaxially purple-red leaflets, but differs from the latter by shorter stature, fewer leaflets ((1-) 3-7) and rays (5-8), the leaflet margin white-ciliate. The new species, which is assessed as Critically Endangered (CR), was only found on limestone cliffs. We also provide a new key to the species of Pternopetalum.

Transabdominal approach for renal cell carcinoma with supradiaphragmatic tumor thrombus: description of a modified technique and indications for treatment.

OBJECTIVE: We investigated the safety and effectiveness of a modified transabdominal approach for renal cell carcinoma (RCC) with a supradiaphragmatic inferior vena cava (IVC) tumor thrombus (TT). METHODS: Eight patients underwent radical nephrectomy with removal of a supradiaphragmatic IVC-TT through an abdominal incision using a transdiaphragmatic approach in Peking University Third Hospital from April 2015 to January 2018. We modified this technique using a Foley catheter balloon to avoid piggyback liver mobilization. RESULTS: All patients underwent successful operations. The median operative time was 7 hours 23 minutes. The median estimated blood loss was 2963 mL. All patients received a blood transfusion with a median blood infusion volume of 2162 mL. Two patients with Budd-Chiari syndrome developed postoperative ascites and hydrothorax due to non-watertight repair of the diaphragm. During a follow-up of 11 to 44 months, only one patient died of liver metastasis and four patients developed distant metastasis without recurrence in the IVC. CONCLUSIONS: The modified transabdominal approach described herein has an encouraging safety profile and provides a surgical option for treatment of RCC with a supradiaphragmatic IVC-TT. More evidence concerning the beneficial role of this procedure will be elucidated in further studies.

Dramatic impact of metric choice on biogeographical regionalization.

For a quantitative biogeographical regionalization, the choice of an appropriate dissimilarity index to measure pairwise distances is crucial. Several different metrics have been used, but there is no specific study to test the impact of metric choice on biogeographical regionalization. We herein applied a hierarchical cluster analysis on the mean nearest taxon distance (MNTD) and the phylogenetic turnover component of the Sørensen dissimilarity index (pßsim) pairwise distances to generate two schemes of phylogenetic regionalization of the Chinese flora, and then evaluated the effect of metric choice. Floristic regionalization based on MNTD was influenced by richness differences, but regionalization based on pßsim can clearly reflect the evolutionary history of the Chinese flora. We provided a brief description of the five regions identified by pßsim, and the regionalization can help develop strategies to effectively conserve the taxa and floristic regions with different origins and evolutionary histories.

Genomic Alterations of Renal Cell Carcinoma and Clinical Implications in the Chinese Population.

BACKGROUND The aim of this study was to investigate the genomic alterations of renal cell carcinoma (RCC) in Chinese patients and to evaluate the correlations between significantly mutated genes and tumor mutation burden (TMB) levels in RCC. MATERIAL AND METHODS Two batch of specimens were collected from patients with RCC. Cohort 1 enrolled 17 RCC patients. Specimens and clinicopathological data were collected and the duration of disease-free survival were evaluated with a follow-up from 2 weeks to longer than 1 year. Cohort 2 collected 70 clear cell RCC (ccRCC) tissues and blood specimens. Next-generation sequencing were used to detect the genomic variations in those specimens in both cohorts and TMB in cohort 2. Clinicopathological features of the 2 cohorts were collected and the χ² test or Fisher's exact test was used for categorical variables stratified by TMB values. RESULTS Our present study demonstrated that the top 3 most frequent aberrated genes in Chinese ccRCC patients were ABCB1, UGT1A1, and VHL, with percentages of 50.00%, 42.86%, and 34.52% respectively. And only 1 gene, which was ABCB1, showed statistically significant difference (P=0.047) stratified by TMB levels. In addition, 6 oncogenic pathways were involved in ccRCC cases in the 2 cohorts. Only 5 out of the 8 most common altered genes of RCC from COSMIC or TCGA databases were detected in our study. CONCLUSIONS The genomic alterations of Chinese RCC patients were different from that in TCGA and COSMIC. No significant genomic alterations were found correlating to TMB levels in ccRCC. Non-silent mutation of VHL may be a predictor for the outcome of ccRCC treated with axitinib.

Phylogenetic delineation of regional biota: A case study of the Chinese flora.

Biogeographical regionalization schemes have traditionally been constructed based on taxonomic endemism of families, genera, and/or species, and rarely incorporated the phylogenetic relationships between taxa. However, phylogenetic relationships are important for understanding historical connections within and among biogeographical regions. Phylogeny-based delineation of biota is a burgeoning and fruitful field that is expected to provide novel insights into the conservation of regional diversity and the evolutionary history of biota. Using the Chinese flora as an example, we compared regionalization schemes that were based on: (1) taxonomic endemism, (2) taxonomic dissimilarity, and (3) phylogenetic dissimilarity. Our results revealed general consistency among different regionalization schemes and demonstrated that the phylogenetic dissimilarity approach is preferable for biogeographical regionalization studies. Using the phylogenetic dissimilarity approach, we identified five phytogeographical regions within China: the Paleotropic, Holarctic, East Asiatic, Tethyan, and Qinghai-Tibet Plateau Regions. The relationship of these regions was inferred to be: (Paleotropic, ((East Asiatic + Holarctic) + (Tethyan + Qinghai-Tibet Plateau)).

Comparison between a novel knotless technique and the conventional single knot technique of laparoscopic radical prostatectomy by novice laparoscopists.

OBJECTIVES: This study aimed to investigate a novel knotless technique for novice laparoscopists in traditional laparoscopic radical prostatectomy. METHODS: We studied 68 patients who had a novel technique performed in laparoscopic radical prostatectomy (knotless group) and 89 who had the conventional single knot technique (single knot group). The operations were all performed by novice laparoscopists with experience of fewer than 100 cases of laparoscopic radical prostatectomy. Knotless suture of the dorsal vein complex was conducted using a barbed self-retaining suture with three bites at the same location. The knotless urethrovesical anastomosis technique was conducted using a unidirectional single running fashion with a barbed self-retaining suture. RESULTS: There were no significant differences in the estimated blood loss, complication rate, postoperative hospital stay, anastomotic leakage rate, continence at 6 months after surgery, and positive margin rate between the two groups. The mean anastomotic time (24.9 vs. 44.2 min), operative time (168.1 vs. 201.8 min), and duration of catheter placement (12.8 vs. 19.8 days) were shorter in the knotless group than in the single-knot group. CONCLUSIONS: The knotless technique of laparoscopic radical prostatectomy is a safe and effective procedure.

Combining complete chloroplast genome sequences with target loci data and morphology to resolve species limits in Triplostegia (Caprifoliaceae).

Species represent the most basic unit of taxonomy. As such, species delimitation represents a crucial issue for biodiversity conservation. Taxonomic practices were revolutionized in the last three decades due to the increasing availability of molecular phylogenetic data. The genus Triplostegia (Caprifoliaceae) traditionally consists of two species, T. glandulifera and T. grandiflora, distinguishable mainly based on quantitative morphological features. In this study, we sequenced nine chloroplast loci (i.e., accD, psbK-psbI, rbcL-accD, rpoB-trnC, rps16-trnQ, trnE-trnT, trnF-ndhJ, trnH-psbA, trnS-trnG) and one nuclear locus (ITS) of 16 individuals of Triplostegia representing the entire distribution range of both species recognized. Furthermore, we also obtained whole chloroplast sequences for 11 of the 16 individuals for which silica gel-dried leaves were available. Our phylogenetic analyses integrating chloroplast genome sequences and multiple loci data revealed that Triplostegia includes four main clades that largely match geography. Neither T. grandiflora nor T. glandulifera was recovered as monophyletic and no diagnosable differences in leaf, flower, and pollen traits were detected between the two species, indicating the need for a revised species circumscription within Triplostegia. Our study highlights the importance of combining data from different sources while defining species limits.