Characterizing complete mitochondrial genome of Aquilegia amurensis and its evolutionary implications.

BACKGROUND: Aquilegia is a model system for studying the evolution of adaptive radiation. However, very few studies have been conducted on the Aquilegia mitochondrial genome. Since mitochondria play a key role in plant adaptation to abiotic stress, analyzing the mitochondrial genome may provide a new perspective for understanding adaptive evolution. RESULTS: The Aquilegia amurensis mitochondrial genome was characterized by a circular chromosome and two linear chromosomes, with a total length of 538,736 bp; the genes included 33 protein-coding genes, 24 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. We subsequently conducted a phylogenetic analysis based on single nucleotide polymorphisms (SNPs) in the mitochondrial genomes of 18 Aquilegia species, which were roughly divided into two clades: the European-Asian clade and the North American clade. Moreover, the genes mttB and rpl5 were shown to be positively selected in European-Asian species, and they may help European and Asian species adapt to environmental changes. CONCLUSIONS: In this study, we assembled and annotated the first mitochondrial genome of the adaptive evolution model plant Aquilegia. The subsequent analysis provided us with a basis for further molecular studies on Aquilegia mitochondrial genomes and valuable information on adaptive evolution in Aquilegia.

Evaluating the ecological vulnerability of Chongqing using deep learning.

This study used deep learning to evaluate the ecological vulnerability of Chongqing, China, discuss the deep learning evaluations of ecological vulnerability, and generate vulnerability maps that support local ecological environment protection and governance decisions and provide reference for future studies. The information gain ratio was used to screen the influencing factors, selecting 16 factors that influence ecological vulnerability. Deep neural network (DNN) and convolutional neural network (CNN) methods were used for modeling, and two ecological vulnerability maps of the study area were generated. The results showed that the mean absolute error and root mean square error of the DNN and CNN models were relatively small, and the fitting accuracy was high. The area under the receiver operating characteristic curve of the CNN model was 0.926, which was better than that of the DNN model (0.888). Random forest was applied to calculate the importance of the influencing factors in the two models. Because the main factor was geological features, the relative ecological vulnerability was mainly affected by karst topography. Through the analysis of the ecological vulnerability map, the areas with higher vulnerability are the karst mountains of Dabashan, Wushan, and Qiyaoshan in the northeast and southeast, as well as the valley between mountains and cities in the center and west of the study area. According to the investigation of these areas, the primary ecological problems are low forest quality, structural irregularities caused by self-geological factors, severe desertification, and soil erosion. Human activity is also an important factor that causes ecological vulnerability in the study area. In conclusion, deep learning, particularly CNN models, can be used for ecological vulnerability assessments. The ecological vulnerability maps conformed to the basic cognition of field surveys and can provide references for other deep learning vulnerability studies. While the overall vulnerability of the study area is not high, ecological problems that lead to its vulnerability should be addressed by future ecological protection and management measures.

Geographic-genomic and geographic-phenotypic differentiation of the Aquilegia viridiflora complex.

How species diverge into different lineages is a central issue in evolutionary biology. Despite the increasing evidence indicating that such divergences do not need geographic isolation, the correlation between lineage divergence and the adaptive ecological divergence of phenotype corresponding to distribution is still unknown. In addition, gene flow has been widely detected during and through such diverging processes. We used one widely distributed Aquilegia viridiflora complex as a model system to examine genomic differentiation and corresponding phenotypic variations along geographic gradients. Our phenotypic analyses of 20 populations from northwest to northeast China identified two phenotypic groups along the geographic cline. All examined traits are distinct from each other, although a few intermediate individuals occur in their contacting regions. We further sequenced the genomes of representative individuals of each population. However, four distinct genetic lineages were detected based on nuclear genomes. In particular, we recovered numerous genetic hybrids in the contact regions of four lineages. Gene flow is widespread and continuous between four lineages but much higher between contacting lineages than geographically isolated lineages. Gene flow and natural selection might result in inconsistency between heredity and phenotype. Moreover, many genes with fast lineage-specific mutations were identified to be involved in local adaptation. Our results suggest that both geographic isolation and local selection exerted by the environment and pollinators may together create geographic distributions of phenotypic variations as well as the underlying genomic divergences in numerous lineages.

A single-cell transcriptome atlas profiles early organogenesis in human embryos.

The early window of human embryogenesis is largely a black box for developmental biologists. Here we probed the cellular diversity of 4-6 week human embryos when essentially all organs are just laid out. On the basis of over 180,000 single-cell transcriptomes, we generated a comprehensive atlas of 313 clusters in 18 developmental systems, which were annotated with a collection of ontology and markers from 157 publications. Together with spatial transcriptome on embryonic sections, we characterized the molecule and spatial architecture of previously unappreciated cell types. Combined with data from other vertebrates, the rich information shed light on spatial patterning of axes, systemic temporal regulation of developmental progression and potential human-specific regulation. Our study provides a compendium of early progenitor cells of human organs, which can serve as the root of lineage analysis in organogenesis.

ZnT8 loss-of-function accelerates functional maturation of hESC-derived ß cells and resists metabolic stress in diabetes.

Human embryonic stem cell-derived ß cells (SC-ß cells) hold great promise for treatment of diabetes, yet how to achieve functional maturation and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remains elusive. Our single-cell RNA-seq analysis reveals that ZnT8 loss of function (LOF) accelerates the functional maturation of SC-ß cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, we demonstrate that ZnT8 LOF mutations endow SC-ß cells with resistance to lipotoxicity/glucotoxicity-triggered cell death by alleviating endoplasmic reticulum (ER) stress through modulation of zinc levels. Importantly, transplantation of SC-ß cells with ZnT8 LOF into mice with preexisting diabetes significantly improves glycemia restoration and glucose tolerance. These findings highlight the beneficial effect of ZnT8 LOF on the functional maturation and survival of SC-ß cells that are useful as a potential source for cell replacement therapies.

Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet ß Cells.

Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic ß cells. Susceptibility and pathogenesis of T2D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq), we demonstrate the presence of sexually dimorphic transcriptomes in mouse ß cells. Using a high-fat diet-induced T2D mouse model, we identified sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sex-matched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway of ß cells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2D pathogenicity, indicating that sex should be considered when treating T2D. We hope that our findings could provide new insights for the development of precision medicine in T2D.

Erector spinae plane block at lower thoracic level for analgesia in lumbar spine surgery: A randomized controlled trial.

BACKGROUND: Patients undergoing lumbar spine surgery usually suffer severe pain in the postoperative period. The erector spinae plane block (ESPB), first published in 2016, can anesthetize the ventral and dorsal rami of thoracic nerves and produce an extensive multi-dermatomal sensory block. AIM: To assess whether bilateral ultrasound-guided ESPB at a lower thoracic level could improve pain control and quality of recovery in patients undergoing lumbar spine surgery. METHODS: A total of 60 patients aged 18-80 years scheduled to undergo lumbar spine surgery with general anesthesia were randomly assigned to two groups: ESPB group (preoperative bilateral ultrasound-guided ESPB at T10 vertebral level) and control group (no preoperative ESPB). Both groups received standard general anesthesia. The main indicator was the duration to the first patient controlled intravenous analgesia (PCIA) bolus. RESULTS: In the ESPB group, the duration to the first PCIA bolus was significantly longer than that in the control group (h) [8.0 (4.5, 17.0) vs 1.0 (0.5, 6), P < 0.01], and resting and coughing numerical rating scale (NRS) scores at 48 h post operation were significantly lower than those in the control group (P < 0.05). There was no significant difference between the two groups regarding resting and coughing NRS scores at 24 h post operation. Sufentanil consumption during the operation was significantly lower in the ESPB group than in the control group (P < 0.01), while there was no significant difference between the two groups regarding morphine consumption at 24 or 48 h post operation. In the ESPB group, Modified Observer's Assessment of Alertness/Sedation score within 20 min after extubation was higher and duration in the post-anesthesia care unit was shorter than those in the control group (P < 0.01). CONCLUSION: In patients undergoing lumbar spine surgery, ultrasound-guided ESPB at a lower thoracic level improves the analgesic effect, reduces opioid consumption, and improves postoperative recovery.

Comparative chloroplast genomes and phylogenetic analysis of Aquilegia.

PREMISE: Aquilegia is an ideal taxon for studying the evolution of adaptive radiation. Current phylogenies of Aquilegia based on different molecular markers are inconsistent, and therefore a clear and accurate phylogeny remains uncertain. Analyzing the chloroplast genome, with its simple structure and low recombination rate, may help solve this problem. METHODS: Next-generation sequencing data were generated or downloaded for Aquilegia species, enabling their chloroplast genomes to be assembled. The assemblies were used to estimate the genome characteristics and infer the phylogeny of Aquilegia. RESULTS: In this study, chloroplast genome sequences were assembled for Aquilegia species distributed across Asia, North America, and Europe. Three of the genes analyzed (petG, rpl36, and atpB) were shown to be under positive selection and may be related to adaptation. The phylogenetic tree of Aquilegia showed that its member species formed two clades with high support, North American and European species, with the Asian species being paraphyletic; A. parviflora and A. amurensis clustered with the North American species, while the remaining Asian species were found in the European clade. In addition, A. oxysepala var. kansuensis should be considered as a separate species rather than a variety. DISCUSSION: The complete chloroplast genomes of these Aquilegia species provide new insights into the reconstruction of the phylogeny of related species and contribute to the further study of this genus.

Bioinformatics analysis of gene and microRNA targets for fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is the most common chronic pain disease in middle-aged women. Patients may also complain of migraine, irritable bowel syndrome and depression, which seriously affect their work and life, causing huge economic losses to society. However, the pathogenesis of FM is still controversial and the effect of the current treatment is far from satisfactory. METHODS: Differentially expressed genes (DEGs) and miRNAs (DEMs) were found between FM and normal blood samples. The pathway and process enrichment analysis of the genes were performed. Protein-protein interaction network were constructed. Hub genes were found and analysed in The Comparative Toxicogenomics Database. RESULTS: A total of 102 genes were up-regulated and 46 down-regulated, 206 miRNAs down-regulated, and 15 up-regulated in FM. CD38, GATM, HDC, FOS were found as canditate genes. These genes were significantly associated with musculoskeletal disease, mental disorder, immune system disease. There was partial overlap between metformin therapy-related genes and FM-related genes. CONCLUSIONS: We found DEGs and DEMs in FM patients through bioinformatics analysis, which may be involved in the occurrence and development of FM and serve as potential targets for diagnosis and treatment.

A single-cell analysis of the molecular lineage of chordate embryogenesis.

Progressive unfolding of gene expression cascades underlies diverse embryonic lineage development. Here, we report a single-cell RNA sequencing analysis of the complete and invariant embryonic cell lineage of the tunicate Ciona savignyi from fertilization to the onset of gastrulation. We reconstructed a developmental landscape of 47 cell types over eight cell cycles in the wild-type embryo and identified eight fate transformations upon fibroblast growth factor (FGF) inhibition. For most FGF-dependent asymmetric cell divisions, the bipotent mother cell displays the gene signature of the default daughter fate. In convergent differentiation of the two notochord lineages, we identified additional gene pathways parallel to the master regulator T/Brachyury Last, we showed that the defined Ciona cell types can be matched to E6.5-E8.5 stage mouse cell types and display conserved expression of limited number of transcription factors. This study provides a high-resolution single-cell dataset to understand chordate early embryogenesis and cell lineage differentiation.

Erector Spinae Plane Block for Lumbar Spinal Surgery: A Systematic Review.

BACKGROUND: Erector spinae plane block (ESPB) as a new trunk fascia block technique was proposed in 2016. ESPB has aroused the interest of many nerve block experts. However, there are few clinical studies on ESPB for lumbar surgery, and its effectiveness and safety are controversial. The goal of this review is to summarize the use of ESPB for lumbar spine surgery in order to better understand this technique. METHODS: PubMed, EMBASE, Cochrane library and ClinicalTrial.gov databases were searched up to July 30, 2019. According to the inclusion and exclusion criteria established in advance, "lumbar spine surgery" and "ESPB" related MesH terms and free-text words were used. Data on pain scores, analgesic consumptions and adverse effects were reported. All processes follow PRISMA statement guidelines. RESULTS: A total of 171 participants from 11 publications were identified, including two randomized controlled trials (RCTs), one retrospective cohort study, four case reports and four cases series. Block operation planes from T8 to L4. The main anesthetics used in the block are bupivacaine, ropivacaine and lidocaine. There was evidence for reducing postoperative pain scores and analgesic consumptions. CONCLUSION: The effectiveness and safety of ESPB for lumbar spine surgery are still controversial. The current evidence is insufficient to support the widespread use of ESPB for lumbar spine surgery. High-quality RCTs are urgently needed.

Bilateral Erector Spinae Plane Blocks for Open Posterior Lumbar Surgery.

PURPOSE: Erector spinae plane block (ESPB) is a newly reported interfascial plane block in pain management, and it can block the nerves exactly in line with the area of the posterior lumbar surgery. The objective of this research was to determine the effectiveness of pre-operative ESPB in enhancing recovery of posterior lumbar surgery. PATIENTS AND METHODS: A total of 60 patients undergoing open posterior lumbar decompression surgery under general anesthesia were randomized into two groups. T12 group was performed pre-operatively bilateral ESPB with ropivacaine at the T12 level, but control group did not receive the block. The primary outcome was the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score at 10 minutes after extubation. Secondary outcomes included intraoperative sufentanil consumption, postoperative morphine consumption, first time to ambulation after surgery and hospital length of stay after surgery. All participants were followed up to hospital discharge. RESULTS: The mean (SD) MOAA/S scores at 10 minutes after extubation were 4.2 (95% CI, 4.0 to 4.4), and 3.4 (95% CI, 3.2 to 3.6) in the T12 and control groups (P <0.001), respectively. Intraoperative sufentanil consumption (P =0.007) and postoperative morphine consumption (P =0.003) were lower in the T12 group than in the control group. Although first time to ambulation after surgery was sooner in the T12 group than in the control group (P =0.003), hospital length of stay was similar (P=0.054). CONCLUSION: Pre-operative bilateral ESPB at T12 can enhance recovery after posterior lumbar surgery and reduce perioperative opioid consumption.

Exploration of the Differentially Expressed Long Noncoding RNAs and Genes of Morphine Tolerance via Bioinformatic Analysis.

Morphine tolerance is one of the most common complications in patients with chronic pain. Many patients with morphine tolerance have poor efficacy in the treatment of primary pain, and are accompanied by the side effects. Previous studies have found that many mechanisms are involved in morphine tolerance, but few researches could fully explain morphine tolerance, and no effective treatment for morphine tolerance has been found. One expression profiling data set was downloaded from the Gene Expression Omnibus (GEO) database. The probes would be transformed into the homologous gene symbol by means of the platform's annotation information. GEO2R was used to search for differentially expressed long noncoding RNAs (lncRNAs) and differentially expressed genes (DEGs) that were differentially expressed between spinal cord samples. Receiver operator characteristic curve analysis was performed to determine the ability of the hub lncRNAs to predict morphine tolerance. Through the principal component analysis, the intragroup data repeatability is fine in the GSE110115. A total of 10 genes were identified as hub genes from the protein-protein interaction network with degrees ≥10. Compared with the normal saline group, the expression levels of LncRNA XR_006440, XR_009493, AF196267, MRAK150340, and MRAK037188 were more downregulated, while the expression levels of MRAK046606, XR_005988, DQ266361, uc.167-, and uc.468+ were more upregulated in the morphine tolerance group. LncRNAs and DEGs were differentially expressed between the morphine tolerance group and nonmorphine tolerance group, which may be involved in the development of morphine tolerance, especially LncRNA DQ266361, uc.167-, and Mmp9, CCL7 genes.

Pivotal micro factors associated with endothelial cells.

OBJECTIVE: Recent studies have shown the important influence of various micro factors on the general biological activity and function of endothelial cells (ECs). Vascular endothelial growth factor (VEGF) and angiogenin (ANG) are classic micro factors that promote proliferation, differentiation, and migration of ECs. The underlying pathophysiological mechanisms and related pathways of these micro factors remain the focus of current research. DATA SOURCES: An extensive search was undertaken in the PubMed database by using keywords including "micro factors" and "endothelial cell." This search covered relevant research articles published between January 1, 2007 and December 31, 2018. STUDY SELECTION: Original articles, reviews, and other articles were searched and reviewed for content on micro factors of ECs. RESULTS: VEGF and ANG have critical functions in the occurrence, development, and status of the physiological pathology of ECs. Other EC-associated micro factors include interleukin 10, tumor protein P53, nuclear factor kappa B subunit, interleukin 6, and tumor necrosis factor. The results of Gene Ontology analysis revealed that variations were mainly enriched in positive regulation of transcription by the RNA polymerase II promoter, cellular response to lipopolysaccharides, negative regulation of apoptotic processes, external side of the plasma membrane, cytoplasm, extracellular regions, cytokine activity, growth factor activity, and identical protein binding. The results of the Kyoto Encyclopedia of Genes and Genomes analysis revealed that micro factors were predominantly enriched in inflammatory diseases. CONCLUSIONS: In summary, the main mediators, factors, or genes associated with ECs include VEGF and ANG. The effect of micro factors on ECs is complex and multifaceted. This review summarizes the correlation between ECs and several micro factors.

Mitigating the adverse impact of batch effects in sample pattern detection.

Motivation: It is well known that batch effects exist in RNA-seq data and other profiling data. Although some methods do a good job adjusting for batch effects by modifying the data matrices, it is still difficult to remove the batch effects entirely. The remaining batch effect can cause artifacts in the detection of patterns in the data. Results: In this study, we consider the batch effect issue in the pattern detection among the samples, such as clustering, dimension reduction and construction of networks between subjects. Instead of adjusting the original data matrices, we design an adaptive method to directly adjust the dissimilarity matrix between samples. In simulation studies, the method achieved better results recovering true underlying clusters, compared to the leading batch effect adjustment method ComBat. In real data analysis, the method effectively corrected distance matrices and improved the performance of clustering algorithms. Availability and implementation: The R package is available at: https://github.com/tengfei-emory/QuantNorm. Supplementary information: Supplementary data are available at Bioinformatics online.