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Peng-Fei Ma,1,* Lin Zhuo,1,* Li-Ping Yuan,2 Xiao-Hui Qi3 1Department of Gastroenterology, Children’s Hospital of Fudan University at Anhui (Anhui Provincial Children’s Hospital), Hefei, Anhui, People’s Republic of China; 2Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Pediatrics, Children’s Hospital of Fudan University at Anhui (Anhui Provincial Children’s Hospital), Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Hui Qi, Department of Pediatrics, Children’s Hospital of Fudan University at Anhui (Anhui Provincial Children’s Hospital), Hefei, Anhui, People’s Republic of China, Email 15955138424@163.comAbstract: Helicobacter pylori (HP) infections affect approximately one-third of children worldwide. In China, the incidence of HP infection in children ranges from approximately 30% to 60%. In addition to damaging the gastrointestinal tract mucosa, HP infection in children can negatively affect their growth and development, hematology, respiratory and hepatobiliary system, skin, nutritional metabolism, and autoimmune system. However, the rate of HP eradication also fell considerably from the previous rate due to the presence of drug-resistant HP strains and the limited types of antibiotics that can be used in young patients. Vitamin D3 (VitD3) is a steroid hormone that can reduce inflammation in the stomach mucosa induced by HP and can alleviate and eradicate HP through a variety of pathways and mechanisms, including immune regulation and the stimulation of antimicrobial peptide (AMP) secretion and Ca2+ influx, to reestablish lysosomal acidification; thus, these results provide new strategies and ideas for the eradication of drug-resistant HP strains.Keywords: vitamin D3, Helicobacter pylori, immune response, AMPs, Ca2+ channels

The woody bamboos (Bambusoideae) exhibit distinctive biological traits within Poaceae, such as highly lignified culms, rapid shoot growth, monocarpic mass flowering and nutlike or fleshy caryopses. Much of the remarkable morphological diversity across the subfamily exists within a single hexaploid clade, the paleotropical woody bamboos (PWB), making it ideal to investigate the factors underlying morphological evolution in woody bamboos. However, the origin and biogeographical history of PWB remain elusive, as does the effect of environmental factors on the evolution of their morphological characters. We generated a robust and time-calibrated phylogeny of PWB using single nucleotide polymorphisms retrieved from optimized double digest restriction site associated DNA sequencing, and explored the evolutionary trends of habit, inflorescence, and caryopsis type in relation to environmental factors including climate, soil, and topography. We inferred that the PWB started to diversify across the Oligocene-Miocene boundary and formed four major clades, that is, Melocanninae, Racemobambosinae s.l. (comprising Dinochloinae, Greslanlinae, Racemobambosinae s.str. and Temburongiinae), Hickeliinae and Bambusinae s.l. (comprising Bambusinae s.str. plus Holttumochloinae). The ancestor of PWB was reconstructed as having erect habit, indeterminate inflorescence and basic caryopsis. The characters including climbing/scrambling habit, determinate inflorescence, and nucoid/bacoid caryopsis have since undergone multiple changes and reversals during the diversification of PWB. The evolution of all three traits was correlated with, and hence likely influenced by, aspects of climate, topography, and soil, with climate factors most strongly correlated with morphological traits, and soil factors least so. However, topography had more influence than climate or soil on the evolution of erect habit, whereas both factors had greater effect on the evolution of bacoid caryopsis than did soil. Our results provide novel insights into morphological diversity and adaptive evolution in bamboos for future ecological and evolutionary research., (© 2024 The Author(s). Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Background: The plastid is the photosynthetic organelle in plant cell, and the plastid genomes (plastomes) are generally conserved in evolution. As one of the most economically and ecologically important order of angiosperms, Poales was previously documented to exhibit great plastomic variation as an order of photoautotrophic plants., Results: We acquired 93 plastomes, representing all the 16 families and 5 major clades of Poales to reveal the extent of their variation and evolutionary pattern. Extensive variation including the largest one in monocots with 225,293 bp in size, heterogeneous GC content, and a wide variety of gene duplication and loss were revealed. Moreover, rare occurrences of three inverted repeat (IR) copies in angiosperms and one IR loss were observed, accompanied by short IR (sIR) and small direct repeat (DR). Widespread structural heteroplasmy, diversified inversions, and unusual genomic rearrangements all appeared in Poales, occasionally within a single species. Extensive repeats in the plastomes were found to be positively correlated with the observed inversions and rearrangements. The variation all showed a "small-large-moderate" trend along the evolution of Poales, as well as for the sequence substitution rate. Finally, we found some positively selected genes, mainly in C 4 lineages, while the closely related lineages of those experiencing gene loss tended to have undergone more relaxed purifying selection., Conclusions: The variation of plastomes in Poales may be related to its successful diversification into diverse habitats and multiple photosynthetic pathway transitions. Our order-scale analyses revealed unusual evolutionary scenarios for plastomes in the photoautotrophic order of Poales and provided new insights into the plastome evolution in angiosperms as a whole., (© 2024. The Author(s).)

Polyploidy (genome duplication) is a pivotal force in evolution. However, the interactions between parental genomes in a polyploid nucleus, frequently involving subgenome dominance, are poorly understood. Here we showcase analyses of a bamboo system (Poaceae: Bambusoideae) comprising a series of lineages from diploid (herbaceous) to tetraploid and hexaploid (woody), with 11 chromosome-level de novo genome assemblies and 476 transcriptome samples. We find that woody bamboo subgenomes exhibit stunning karyotype stability, with parallel subgenome dominance in the two tetraploid clades and a gradual shift of dominance in the hexaploid clade. Allopolyploidization and subgenome dominance have shaped the evolution of tree-like lignified culms, rapid growth and synchronous flowering characteristic of woody bamboos as large grasses. Our work provides insights into genome dominance in a remarkable polyploid system, including its dependence on genomic context and its ability to switch which subgenomes are dominant over evolutionary time., (© 2024. The Author(s).)

Current biodiversity loss is generally considered to have been caused by anthropogenic disturbance, but it is unclear when anthropogenic activities began to affect biodiversity loss. One hypothesis suggests it began with the Industrial Revolution, whereas others propose that anthropogenic disturbance has been associated with biodiversity decline since the early Holocene. To test these hypotheses, we examined the unique vegetation of evergreen broadleaved forests (EBLFs) in East Asia, where humans have affected landscapes since the early Holocene. We adopted a genomic approach to infer the demographic history of a dominant tree (Litsea elongata) of EBLFs. We used Holocene temperature and anthropogenic disturbance factors to calculate the correlation between these variables and the historical effective population size of L. elongata with Spearman statistics and integrated the maximum-entropy niche model to determine the impact of climate change and anthropogenic disturbance on fluctuation in its effective population size. We identified 9 well-defined geographic clades for the populations of L. elongata. Based on the estimated historical population sizes of these clades, all the populations contracted, indicating persistent population decline over the last 11,000 years. Demographic history of L. elongata and human population change, change in cropland use, and change in irrigated rice area were significantly negatively correlated, whereas climate change in the Holocene was not correlated with demographic history. Our results support the early human impact hypothesis and provide comprehensive evidence that early anthropogenic disturbance may contribute to the current biodiversity crisis in East Asia., (© 2023 Society for Conservation Biology.)

Background: Stomatal variation, including guard cell (GC) density, size and chloroplast number, is often used to differentiate polyploids from diploids. However, few works have focused on stomatal variation with respect to polyploidization, especially for consecutively different ploidy levels within a plant species. For example, Allium tuberosum, which is mainly a tetraploid (2n = 4x = 32), is also found at other ploidy levels which have not been widely studied yet., Results: We recently found cultivars with different ploidy levels, including those that are diploid (2n = 2x = 16), triploid (2n = 3x = 24), pseudopentaploid (2n = 34-42, mostly 40) and pseudohexaploid (2n = 44-50, mostly 48). GCs were evaluated for their density, size (length and width) and chloroplast number. There was no correspondence between ploidy level and stomatal density, in which anisopolyploids (approximately 57 and 53 stomata/mm 2 in triploid and pseudopentaploid, respectively) had a higher stomatal density than isopolyploids (approximately 36, 43, and 44 stomata/mm 2 in diploid, tetraploid and pseudohexaploid, respectively). There was a positive relationship between ploidy level and GC chloroplast number (approximately 44, 45, 51, 72 and 90 in diploid to pseudohexaploid, respectively). GC length and width also increased with ploidy level. However, the length increased approximately 1.22 times faster than the width during polyploidization., Conclusions: This study shows that GC size increased with increasing DNA content, but the rate of increase differed between length and width. In the process of polyploidization, plants evolved longer and narrower stomata with more chloroplasts in the GCs., (© 2023. The Author(s).)

The evergreen versus deciduous leaf habit is an important functional trait for adaptation of forest trees and has been hypothesized to be related to the evolutionary processes of the component species under paleoclimatic change, and potentially reflected in the dynamic history of evergreen broadleaved forests (EBLFs) in East Asia. However, knowledge about the shift of evergreen versus deciduous leaf with the impact of paleoclimatic change using genomic data remains rare. Here, we focus on the Litsea complex (Lauraceae), a key lineage with dominant species of EBLFs, to gain insights into how evergreen versus deciduous trait shifted, providing insights into the origin and historical dynamics of EBLFs in East Asia under Cenozoic climate change. We reconstructed a robust phylogeny of the Litsea complex using genome-wide single-nucleotide variants (SNVs) with eight clades resolved. Fossil-calibrated analyses, diversification rate shifts, ancestral habit, ecological niche modelling and climate niche reconstruction were employed to estimate its origin and diversification pattern. Taking into account studies on other plant lineages dominating EBLFs of East Asia, it was revealed that the prototype of EBLFs in East Asia probably emerged in the Early Eocene (55-50 million years ago [Ma]), facilitated by the greenhouse warming. As a response to the cooling and drying climate in the Middle to Late Eocene (48-38 Ma), deciduous habits were evolved in the dominant lineages of the EBLFs in East Asia. Up to the Early Miocene (23 Ma), the prevailing of East Asian monsoon increased the extreme seasonal precipitation and accelerated the emergence of evergreen habits of the dominant lineages, and ultimately shaped the vegetation resembling that of today., (© 2023 John Wiley & Sons Ltd.)

Background: Helicobacter pylori (HP) is a major cause of upper digestive tract diseases. However, the relationship between HP infection and 25-hydroxyvitamin D [25(OH)D] levels in children has not been fully elucidated. This study investigated the levels of 25(OH)D in children of different ages and with varying degrees of HP infection and immunological features as well as the correlations between 25(OH)D levels in children infected with HP and their ages and degrees of infection., Materials and Methods: Ninety-four children who underwent upper digestive endoscopy were divided into an HP-positive group without peptic ulcers (Group A), an HP-positive group with peptic ulcers (Group B) and an HP-negative control group (Group C). The serum levels of 25(OH)D and immunoglobulin and the percentages of lymphocyte subsets were determined. HP colonization, the degree of inflammation, and the degree of activity were further evaluated by HE staining and immunohistochemical staining in gastric mucosal biopsy., Results: The 25(OH)D level of the HP-positive groups (50.93 ± 16.51 nmol/L) was significantly lower than that of the HP-negative group (62.89 ± 19.18 nmol/L). The 25(OH)D level of Group B (47.79 ± 14.79 nmol/L) was lower than that of Group A (51.53 ± 17.05 nmol/L) and was significantly lower than that of Group C (62.89 ± 19.18 nmol/L). The 25(OH)D level decreased with increasing age, and there was a significant difference between Group C subjects who were ≤5 years old and those who were aged 6-9 years and ≥10 years. The 25(OH)D level was negatively correlated with HP colonization ( r  = -0.411, P  < 0.01) and the degree of inflammation ( r  = -0.456, P  < 0.01). The percentages of lymphocyte subsets and immunoglobulin levels among Groups A, B and C were not significantly different., Conclusions: The 25(OH)D level was negatively correlated with HP colonization and the degree of inflammation. As the age of the children increased, the level of 25(OH)D decreased, and the susceptibility to HP infection increased., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ma, Dai, Chu, Zhuo, Chen, Cheng, Wu and Yuan.)

Main Conclusion: CG and CHG methylation levels in the rapid shoot growth stages (ST2-ST4) of woody bamboos were obviously decreased, which might regulate the internode elongation during rapid shoot growth, while CHH methylation was strongly associated with shoot developmental time or age. DNA methylation plays a critical role in the regulation of plant growth and development. Woody bamboos have a unique trait of rapid stem growth resulted from internode elongation at the shooting period. However, it is still unclear whether DNA methylation significantly controls the bamboo rapid stem growth. Here we present whole-genome DNA methylation profiles of the paleotropical woody bamboo Bonia amplexicaulis at five newly defined stages of shoot growth, named ST1-ST5. We found that CG and CHG methylation levels in the rapid shoot growth stages (ST2-ST4) were significantly lower than in the incubation (ST1) and plateau stages (ST5). The changes in methylation levels mainly occurred in flanking regions of genes and gene body regions, and 23647 differentially methylated regions (DMRs) were identified between ST1 and rapid shoot growth stages (ST2-ST4). Combined with transcriptome analysis, we found that DMR-related genes enriched in the auxin and jasmonic acid (JA) signal transduction, and other pathways closely related to plant growth. Intriguingly, CHH methylation was not involved in the rapid shoot growth, but strongly associated with shoot developmental time by gradually accumulating in transposable elements (TEs) regions. Overall, our results reveal the importance of DNA methylation in regulating the bamboo rapid shoot growth and suggest a role of DNA methylation associated with development time or age in woody bamboos., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fargesia , the largest genus within the temperate bamboo tribe Arundinarieae, has more than 90 species mainly distributed in the mountains of Southwest China. The Fargesia bamboos are important components of the subalpine forest ecosystems that provide food and habitat for many endangered animals, including the giant panda. However, species-level identification of Fargesia is difficult. Moreover, the rapid radiation and slow molecular evolutionary rate of Fargesia pose a significant challenge to using DNA barcoding with standard plant barcodes ( rbcL , matK , and ITS) in bamboos. With progress in the sequencing technologies, complete plastid genomes (plastomes) and nuclear ribosomal DNA (nrDNA) sequences have been proposed as organelle barcodes for species identification; however, these have not been tested in bamboos. We collected 196 individuals representing 62 species of Fargesia to comprehensively evaluate the discriminatory power of plastomes and nrDNA sequences compared to standard barcodes. Our analysis indicates that complete plastomes have substantially higher discriminatory power (28.6%) than standard barcodes (5.7%), whereas nrDNA sequences show a moderate improvement (65.4%) compared to ITS (47.2%). We also found that nuclear markers performed better than plastid markers, and ITS alone had higher discriminatory power than complete plastomes. The study also demonstrated that plastomes and nrDNA sequences can contribute to intrageneric phylogenetic resolution in Fargesia . However, neither of these sequences were able to discriminate all the sampled species, and therefore, more nuclear markers need to be identified., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by.)

Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) play critical roles in tumorigenesis. However, the mechanisms underlying MDSC and TAM development and function remain unclear. In this study, we find that myeloid-specific activation of Notch/RBP-J signaling downregulates lactate transporter MCT2 transcription via its downstream molecule Hes1, leading to reduced intracellular lactate levels, blunted granulocytic MDSC (G-MDSC) differentiation, and enhanced TAM maturation. We identify c-Jun as a novel intracellular sensor of lactate in myeloid cells using liquid-chromatography-mass spectrometry (LC-MS) followed by CRISPR-Cas9-mediated gene disruption. Meanwhile, lactate interacts with c-Jun to protect from FBW7 ubiquitin-ligase-mediated degradation. Activation of Notch signaling and blockade of lactate import repress tumor progression by remodeling myeloid development. Consistently, the relationship between the Notch-MCT2/lactate-c-Jun axis in myeloid cells and tumorigenesis is also confirmed in clinical lung cancer biopsies. Taken together, our current study shows that lactate metabolism regulated by activated Notch signaling might participate in MDSC differentiation and TAM maturation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Solute carrier family 25 member 20 (SLC25A51) is a newly identified mammalian mitochondrial NAD + transporter. However, the clinicopathological and biological significance of SLC25A51 in human cancers, including hepatocellular carcinoma (HCC), remains unclear. The aim of this study was to define the role of SLC25A51 in HCC progression. Here we demonstrate that SLC25A51 is significantly overexpressed in human HCC specimens and cell lines, caused by, at least in partial, the decrease of miR-212-3p. SLC25A51 overexpression is positively correlated with the clinicopathological characteristics of vascular invasion and tumor diameter, as well as poor survival in patients with HCC. Knockdown of SLC25A51 attenuated, while overexpression of SLC25A51 enhanced the growth and metastasis of HCC cells both in vitro and in vivo. Mechanistically, glucose metabolism reprogramming from oxidative phosphorylation to glycolysis by activation of mitochondrial sirtuin 5 (SIRT5) was found to contribute to the promotion of growth and metastasis by SLC25A51 in HCC cells. Together, these findings reveal important roles of SLC25A51 in HCC tumorigenesis and suggest SLC25A51 as a promising prognostic marker and therapeutic target for treating HCC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The Poales is one of the largest orders of flowering plants with significant economic and ecological values. Reconstructing the phylogeny of the Poales is important for understanding its evolutionary history that forms the basis for biological studies. However, due to sparse taxon sampling and limited molecular data, previous studies have resulted in a variety of contradictory topologies. In particular, there are three nodes surrounded by incongruence: the phylogenetic ambiguity near the root of the Poales tree, the sister family of Poaceae, and the delimitation of the xyrid clade. We conducted a comprehensive sampling and reconstructed the phylogenetic tree using plastid and mitochondrial genomic data from 91 to 66 taxa, respectively, representing all the 16 families of Poales. Our analyses support the finding of Bromeliaceae and Typhaceae as the earliest diverging groups within the Poales while having phylogenetic relationships with the polytomy. The clade of Ecdeiocoleaceae and Joinvilleaceae is recovered as the sister group of Poaceae. The three families, Mayacaceae, Eriocaulaceae, and Xyridaceae, of the xyrid assembly diverged successively along the backbone of the Poales phylogeny, and thus this assembly is paraphyletic. Surprisingly, we find substantial phylogenetic conflicts within the plastid genomes of the Poales, as well as among the plastid, mitochondrial, and nuclear data. These conflicts suggest that the Poales could have a complicated evolutionary history, such as rapid radiation and polyploidy, particularly allopolyploidy through hybridization. In sum, our study presents a new perspicacity into the complex phylogenetic relationships and the underlying phylogenetic conflicts within the Poales., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Yang, Liu, Li and Ma.)

The two microRNAs miR-192 and miR-194 are abundantly expressed in the liver and are considered serum biomarkers of liver injury. However, their role in the development of liver injury has not yet been determined. In this study, we generated miR-192/194 mutant mice and determined the effect of miR-192/194 loss on acetaminophen (APAP)-induced acute liver injury. With genetic depletion of miR-192/194, mutant mice were fertile and normally developed. No spontaneous liver injuries were observed in mutant mice. After APAP administration, mutant mice developed less severe liver damage than control mice. Specifically, mutant mice exhibited significantly lower serum alanine transaminase (ALT) levels and pericentral necrosis/apoptosis than control mice receiving APAP. β-catenin signaling was activated during the early phase of liver injury. Activated β-catenin signaling led to faster cellular proliferation and higher expression of AXIN2 and glutamine synthetases. After partial hepatectomy, the miR-192/194 mutant hepatocytes were more regenerative than control hepatocytes (as shown by BrdU incorporation). Moreover, in vitro experiments indicated that miR-194, but not miR-192, specifically repressed β-catenin signaling, while animal experiments revealed that chemical-mediated knockdown of β-catenin signaling compromised APAP resistance that liver protected from miR-192/194 genetic depletion. Collectively, our data indicated that the loss of miR-194 promoted liver regeneration and protected the liver from APAP-induced injury., (Copyright © 2021 Elsevier Inc. All rights reserved.)

As drivers of evolutionary innovations, new genes allow organisms to explore new niches. However, clear examples of this process remain scarce. Bamboos, the unique grass lineage diversifying into the forest, have evolved with a key innovation of fast growth of woody stem, reaching up to 1 m/day. Here, we identify 1,622 bamboo-specific orphan genes that appeared in recent 46 million years, and 19 of them evolved from noncoding ancestral sequences with entire de novo origination process reconstructed. The new genes evolved gradually in exon-intron structure, protein length, expression specificity, and evolutionary constraint. These new genes, whether or not from de novo origination, are dominantly expressed in the rapidly developing shoots, and make transcriptomes of shoots the youngest among various bamboo tissues, rather than reproductive tissue in other plants. Additionally, the particularity of bamboo shoots has also been shaped by recent whole-genome duplicates (WGDs), which evolved divergent expression patterns from ancestral states. New genes and WGDs have been evolutionarily recruited into coexpression networks to underline fast-growing trait of bamboo shoot. Our study highlights the importance of interactions between new genes and genome duplicates in generating morphological innovation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Background: Flowering plants (angiosperms) are dominant components of global terrestrial ecosystems, but phylogenetic relationships at the familial level and above remain only partially resolved, greatly impeding our full understanding of their evolution and early diversification. The plastome, typically mapped as a circular genome, has been the most important molecular data source for plant phylogeny reconstruction for decades., Results: Here, we assembled by far the largest plastid dataset of angiosperms, composed of 80 genes from 4792 plastomes of 4660 species in 2024 genera representing all currently recognized families. Our phylogenetic tree (PPA II) is essentially congruent with those of previous plastid phylogenomic analyses but generally provides greater clade support. In the PPA II tree, 75% of nodes at or above the ordinal level and 78% at or above the familial level were resolved with high bootstrap support (BP ≥ 90). We obtained strong support for many interordinal and interfamilial relationships that were poorly resolved previously within the core eudicots, such as Dilleniales, Saxifragales, and Vitales being resolved as successive sisters to the remaining rosids, and Santalales, Berberidopsidales, and Caryophyllales as successive sisters to the asterids. However, the placement of magnoliids, although resolved as sister to all other Mesangiospermae, is not well supported and disagrees with topologies inferred from nuclear data. Relationships among the five major clades of Mesangiospermae remain intractable despite increased sampling, probably due to an ancient rapid radiation., Conclusions: We provide the most comprehensive dataset of plastomes to date and a well-resolved phylogenetic tree, which together provide a strong foundation for future evolutionary studies of flowering plants., (© 2021. The Author(s).)

Rapid evolutionary radiations are among the most challenging phylogenetic problems, wherein different types of data (e.g., morphology and molecular) or genetic markers (e.g., nuclear and organelle) often yield inconsistent results. The tribe Arundinarieae, that is, the temperate bamboos, is a clade of tetraploid originated 22 Ma and subsequently radiated in East Asia. Previous studies of Arundinarieae have found conflicting relationships and/or low support. Here, we obtain nuclear markers from ddRAD data for 213 Arundinarieae taxa and parallel sampling of chloroplast genomes from genome skimming for 147 taxa. We first assess the feasibility of using ddRAD-seq data for phylogenetic estimates of paleopolyploid and rapidly radiated lineages, optimize clustering thresholds, and analysis workflow for orthology identification. Reference-based ddRAD data assembly approaches perform well and yield strongly supported relationships that are generally concordant with morphology-based taxonomy. We recover five major lineages, two of which are notable (the pachymorph and leptomorph lineages), in that they correspond with distinct rhizome morphologies. By contrast, the phylogeny from chloroplast genomes differed significantly. Based on multiple lines of evidence, the ddRAD tree is favored as the best species tree estimation for temperate bamboos. Using a time-calibrated ddRAD tree, we find that Arundinarieae diversified rapidly around the mid-Miocene corresponding with intensification of the East Asian monsoon and the evolution of key innovations including the leptomorph rhizomes. Our results provide a highly resolved phylogeny of Arundinarieae, shed new light on the radiation and reticulate evolutionary history of this tribe, and provide an empirical example for the study of recalcitrant plant radiations. [Arundinarieae; ddRAD; paleopolyploid; genome skimming; rapid diversification; incongruence.]., (© The Author(s) 2020. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.)

The grass family (Poaceae) includes all commercial cereal crops and is a major contributor to biomass in various terrestrial ecosystems. The ancestry of all grass genomes includes a shared whole-genome duplication (WGD), named rho (ρ) WGD, but the evolutionary significance of ρ-WGD remains elusive. We sequenced the genome of Pharus latifolius, a grass species (producing a true spikelet) in the subfamily Pharoideae, a sister lineage to the core Poaceae including the (Panicoideae, Arundinoideae, Chloridoideae, Micrairoideae, Aristidoideae, and Danthonioideae (PACMAD) and Bambusoideae, Oryzoideae, and Pooideae (BOP) clades. Our results indicate that the P. latifolius genome has evolved slowly relative to cereal grass genomes, as reflected by moderate rates of molecular evolution, limited chromosome rearrangements and a low rate of gene loss for duplicated genes. We show that the ρ-WGD event occurred approximately 98.2 million years ago (Ma) in a common ancestor of the Pharoideae and the PACMAD and BOP grasses. This was followed by contrasting patterns of diploidization in the Pharus and core Poaceae lineages. The presence of two FRIZZY PANICLE-like genes in P. latifolius, and duplicated MADS-box genes, support the hypothesis that the ρ-WGD may have played a role in the origin and functional diversification of the spikelet, an adaptation in grasses related directly to cereal yields. The P. latifolius genome sheds light on the origin and early evolution of grasses underpinning the biology and breeding of cereals., (� American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

MicroRNA-27 is a critical non-coding metabolic gene that is often aberrantly overexpressed in non-alcoholic fatty livers (NAFLD). However, the pathogenic role of miR-27 in NAFLD remains unknown. In this study, we attempted to identify the mechanism by which miR-27 was regulated in the context of insulin resistance, a predisposed metabolic disorder in NAFLD. Our data from cell culture and animal studies showed that insulin, CREB, and Hippo signalings coordinately regulated miR-27. First, miR-27 was upregulated in palmitate-treated cells and high fat diet-fed mouse livers, which exhibited insulin resistance and CREB overexpression. Second, miR-27 peaked in the mouse liver at the post-absorptive phase when CREB activity was increased. Also, miR-27 was increased rapidly in cell lines when CREB was deactivated by insulin treatment. Third, miR-27 was decreased in cultured cells when CREB was downregulated by siRNA or metformin treatment. In contrast, Forskolin-mediated activation of CREB promoted miR-27 expression. Fourth, Hippo signaling repressed miR-27 in a CREB-independent manner: miR-27 was reduced in cells at full confluence but was inhibited in cells transfected with siRNA against Lats2 and Nf2, which were two positive regulators of Hippo signaling. Lastly, bioinformatics and luciferase assay showed that miR-27 inhibited Akt phosphorylation by targeting Pdpk1 and Pik3r1. Overexpression of miR-27 impaired Akt phosphorylation in cell lines and primary mouse hepatocytes upon insulin stimulation. In conclusion, our data suggest that insulin, CREB, and Hippo signalings contribute to aberrant miR-27 overexpression and eventually lead to insulin resistance in NAFLD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Depression is a disease with a high incidence and easy to relapse. It not only affects the work and life of patients, but also brings a heavy economic burden. University is the peak of depression, and the prevalence of depression among college students is much higher than that of ordinary people. The purpose of this research is to evaluate depression symptoms, life satisfaction, self-confidence, substance use, social adjustment, and dropout rates of the use of psychological intervention for college students., Methods: We will identify relevant trials from systematic searches in the following electronic databases: PubMed, Embase, Web of Science and The Cochrane Library. We will also search Clinical Trials.gov, the WHO International Clinical Trials Registry Platform for unpublished data. Additional relevant studies will be searched through search engines (such as Google), and references included in the literature will be tracked. All relevant randomized controlled trials (RCTs) will be included. There are no date restrictions. Use Cochrane Collaboration's Risk of bias tool to conduct risk of bias analysis. Use the Grades of Recommendation, Assessment, Development, and Evaluation to assess the quality of evidence. All statistical analysis will be performed using Stata (V.15.0.) and Review Manager (V.5.2.0)., Results: A total of 6238 records were obtained by searching the database and 27 records were obtained by other sources. After removing duplicate records, there are 4225 records remaining. We excluded 3945 records through abstract and title, leaving 280 full-text articles., Conclusion: This will be the first study to compare the effects of different psychological treatments on depression in college students. We hope that this study will guide clinical decision-making of psychotherapy to better treat depression in college students., Protocol Registration: INPLASY202070134.

Salvia is the largest genus of Lamiaceae, with almost 1000 species, and has been divided into 11 subgenera. Salvia subg. Glutinaria , native to East Asia, is particularly important because of its potential medicinal value. However, the interspecific relationships of this subgenus have not been resolved and the plastomes of Salvia have rarely been studied. In the current study, we compared plastid genome structure and organization of 19 species of Salvia (14 newly sequenced and 5 previously published). Our comparative analysis showed that all Salvia plastomes examined have a quadripartite structure typical of most angiosperms and contain an identical set of 114 unique genes (80 protein-coding genes, 4 rRNA genes, and 30 tRNA genes). The plastome structure of all Salvia species is highly conserved like other Lamiaceae plastomes. Gene content, gene order, and GC content were highly similar in these plastomes. The inverted repeats/single copy region (IR/SC) boundaries of Salvia are highly conserved, and IR contraction only occurred in two species ( Salvia mekongensis and S. rosmarinus ). In Salvia , sequence divergence was higher in non-coding regions than in coding regions. We found that using large single copy (LSC) and small single copy regions (SSC) with exclusion of the rapidly evolving sites produced the highest resolution in phylogenetic analysis of Salvia , suggesting that using suitable informative sites to build trees is more conducive in phylogenetic research. This study assembled a powerful matrix data set for studying the phylogeny of Salvia , resolving the interspecific relationship of Salvia subg. Glutinaria . The newly sequenced plastid genomes will also enrich the plastome database of Salvia , providing the scientific basis for the development and utilization of germplasm resources of this large and important genus., Competing Interests: The authors declared that they have no conflict of interest., (© 2020 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

The Bambusa-Dendrocalamus-Gigantochloa complex (BDG complex) is the most diversified and phylogenetically recalcitrant group of the paleotropical woody bamboos. Species of this complex occur in tropical and subtropical Asia and most of them are of great economic, cultural and ecological value. The lack of resolution achieved through the analyses of previous molecular datasets has long confounded its phylogenetic estimation and generic delimitation. Here, we adopted a ddRAD-seq strategy to investigate phylogenetic relationships of the four main genera (Bambusa, Dendrocalamus, Gigantochloa, and Melocalamus) in the BDG complex. A total of 102 species were sampled, and SNP data were generated. Both MP and ML analyses of the ddRAD-seq data resulted in a well-resolved topology with Gigantochloa and Melocalamus confirmed as monophyletic, and Melocalamus resolved as sister to the rest of the complex. Bambusa and Dendrocalamus were both resolved as paraphyletic. The phylogenetic relationships were mostly supported by morphological evidence including characters of the branch complement, rachilla, lodicules, filaments and stigma. We also generated and assembled complete plastid genomes of 48 representative species. There were conflicts between the plastome and the ddRAD topologies. Our study demonstrated that RAD-seq can be used to reconstruct evolutionary history of lineages such as the bamboos where ancient hybridization and polyploidy play a significant role. The four genera of the BDG complex have a complex evolutionary history which is likely a product of ancient introgression events., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Nitroglycerin (NTG), a nitric oxide-donating drug, may increase tumor blood flow and consequently increase cancer drug delivery to tumor cells. Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of deoxythymidine monophosphate; we had found that knocking down the expression of TS sensitizes lung cancer cells to cisplatin-induced cytotoxicity. However, whether NTG and cisplatin could induce synergistic cytotoxicity in nonsmall cell lung cancer (NSCLC) cells through modulating TS expression is unknown. In this study, NTG decreased TS expression in an AKT, also known as Protein kinase B (PKB) inactivation dependent manner in human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Enhancement of AKT activity by transfection with constitutive active AKT vectors increased the TS expression level as well as the cell survival pretreated by NTG. Moreover, NTG synergistically enhanced cytotoxicity and cell growth inhibition by cisplatin treatment in NSCLC cells, which were associated with downregulation of TS expression and inactivation of AKT in A549 and H1703 cells. Together, these results may provide a rationale to combine NTG with cisplatin-based chemotherapy to enhance the therapeutic effect for lung cancer in the future., (© 2019 S. Karger AG, Basel.)

Polyploidization is a major driver of speciation and its importance to plant evolution has been well recognized. Bamboos comprise one diploid herbaceous and three polyploid woody lineages, and are members of the only major subfamily in grasses that diversified in forests, with the woody members having a tree-like lignified culm. In this study, we generated four draft genome assemblies of major bamboo lineages with three different ploidy levels (diploid, tetraploid, and hexaploid). We also constructed a high-density genetic linkage map for a hexaploid species of bamboo, and used a linkage-map-based strategy for genome assembly and identification of subgenomes in polyploids. Further phylogenomic analyses using a large dataset of syntenic genes with expected copies based on ploidy levels revealed that woody bamboos originated subsequent to the divergence of the herbaceous bamboo lineage, and experienced complex reticulate evolution through three independent allopolyploid events involving four extinct diploid ancestors. A shared but distinct subgenome was identified in all polyploid forms, and the progenitor of this subgenome could have been critical in ancient polyploidizations and the origin of woody bamboos. Important genetic clues to the unique flowering behavior and woody trait in bamboos were also found. Taken together, our study provides significant insights into ancient reticulate evolution at the subgenome level in the absence of extant donor species, and offers a potential model scenario for broad-scale study of angiosperm origination by allopolyploidization., (Copyright © 2019 The Author. Published by Elsevier Inc. All rights reserved.)

With the development of sequencing technologies, the use of multiple nuclear genes has become conventional for resolving difficult phylogenies. However, this technique also presents challenges due to gene-tree discordance, as a result of incomplete lineage sorting (ILS) and reticulate evolution. Although alleles can show sequence variation within individuals, which contain information regarding the evolution of organisms, they continue to be ignored in almost all phylogenetic analyses using randomly phased genome sequences. Here, we tried to incorporate alleles from multiple nuclear loci to study the phylogeny of the economically important bamboo genus Phyllostachys (Poaceae, Bambusoideae). Obtaining a total of 3926 sequences, we documented extensive allelic variation for 61 genes from 39 sampled species. Using datasets consisting of selected alleles, we demonstrated substantial discordance among phylogenetic relationships inferred from different alleles, as well as between concatenation and coalescent methods. Furthermore, ILS and hybridization were suggested to be underlying causes of the discordant phylogenetic signals. Taking these possible causes for conflicting phylogenetic results into consideration, we recovered the monophyly of Phyllostachys and its two morphology-defined sections. Our study also suggests that alleles deserve more attention in phylogenetic studies, since ignoring them can yield highly supported but spurious phylogenies. Meanwhile, alleles are helpful for unraveling complex evolutionary processes, particularly hybridization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this manuscript, the nonlinear absorption properties of Cr 2 Ge 2 Te 6 and its application in ultra-fast optical modulation are investigated. Typical parameters, namely, nonlinear absorption coefficient (β), saturation intensity, and modulation depth are measured to be ~1.66 × 10 -9 m/W, 15.3 MW/cm 2 , and 5.8%, respectively. To investigate the feasibility of using the Cr 2 Ge 2 Te 6 as an ultra-fast optical modulator, a ring-cavity passively mode-locked Er-doped fiber laser has been constructed. The output power/pulse, duration/pulse, and repetition rate/signal-to-noise ratios for the stable mode-locked operation are 2.88 mW/881 fs/19.33 MHz/48 dB, respectively, which proves that the Cr 2 Ge 2 Te 6 has outstanding nonlinear optical properties and advantages in performing as an ultra-fast optical modulator. Further, the experimental results provide valuable references and open new avenues for developing two-dimensional, material-based, ultra-fast optical modulators and advanced photonic devices based on Cr 2 Ge 2 Te 6 .

Angiosperms are by far the most species-rich clade of land plants, but their origin and early evolutionary history remain poorly understood. We reconstructed angiosperm phylogeny based on 80 genes from 2,881 plastid genomes representing 85% of extant families and all orders. With a well-resolved plastid tree and 62 fossil calibrations, we dated the origin of the crown angiosperms to the Upper Triassic, with major angiosperm radiations occurring in the Jurassic and Lower Cretaceous. This estimated crown age is substantially earlier than that of unequivocal angiosperm fossils, and the difference is here termed the 'Jurassic angiosperm gap'. Our time-calibrated plastid phylogenomic tree provides a highly relevant framework for future comparative studies of flowering plant evolution.

Lycophytes are a key group for understanding vascular plant evolution. Lycophyte plastomes are highly distinct, indicating a dynamic evolutionary history, but detailed evaluation is hindered by the limited availability of sequences. Eight diverse plastomes were sequenced to assess variation in structure and functional content across lycophytes. Lycopodiaceae plastomes have remained largely unchanged compared with the common ancestor of land plants, whereas plastome evolution in Isoetes and especially Selaginella is highly dynamic. Selaginella plastomes have the highest GC content and fewest genes and introns of any photosynthetic land plant. Uniquely, the canonical inverted repeat was converted into a direct repeat (DR) via large-scale inversion in some Selaginella species. Ancestral reconstruction identified additional putative transitions between an inverted and DR orientation in Selaginella and Isoetes plastomes. A DR orientation does not disrupt the activity of copy-dependent repair to suppress substitution rates within repeats. Lycophyte plastomes include the most archaic examples among vascular plants and the most reconfigured among land plants. These evolutionary trends correlate with the mitochondrial genome, suggesting shared underlying mechanisms. Copy-dependent repair for DR-localized genes indicates that recombination and gene conversion are not inhibited by the DR orientation. Gene relocation in lycophyte plastomes occurs via overlapping inversions rather than transposase/recombinase-mediated processes., (© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.)

Salinomycin is a polyether ionophore antibiotic having anti-tumorigenic property in various types of cancer. Elevated thymidine phosphorylase (TP) levels, a key enzyme in the pyrimidine nucleoside salvage pathway, are associated with an aggressive disease phenotype and poor prognoses. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. In this study, we report whether Hsp90 inhibitor 17-AAG could enhance salinomycin-induced cytotoxicity in NSCLC cells through modulating TP expression in two non-small-cell lung cancer (NSCLC) cell lines, A549 and H1975. We found that salinomycin increased TP expression in a MKK3/6-p38 MAPK activation manner. Knockdown of TP using siRNA or inactivation of p38 MAPK by pharmacological inhibitor SB203580 enhanced the cytotoxic and growth inhibition effects of salinomycin. In contrast, enforced expression of MKK6E (a constitutively active form of MKK6) reduced the cytotoxicity and cell growth inhibition of salinomycin. Moreover, Hsp90 inhibitor 17-AAG enhanced cytotoxicity and cell growth inhibition of salinomycin in NSCLC cells, which were associated with down-regulation of TP expression and inactivation of p38 MAPK. Together, the Hsp90 inhibition induced TP down-regulation involved in enhancing the salinomycin-induced cytotoxicity in A549 and H1975 cells., (Copyright © 2019. Published by Elsevier B.V.)

Capsaicin, a natural active ingredient of green and red peppers, has been demonstrated to exhibit anti-cancer properties in several malignant cell lines. Excision repair cross-complementary 1 (ERCC1) has a leading role in the nucleotide excision repair (NER) process because of its involvement in the excision of DNA adducts. Erlotinib (Tarceva R ) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated clinical activity in non-small cell lung cancer (NSCLC) cells. However, whether capsaicin and erlotinib could induce synergistic cytotoxicity in NSCLC cells through modulating ERCC1 expression is unknown. In this study, capsaicin decreased the ERCC1 expression in an AKT inactivation dependent manner in two human lung adenocarcinoma cells, namely, A549 and H1975. Enhancement of AKT activity by transfection with constitutive active AKT vectors increased the ERCC1 protein level as well as the cell survival by capsaicin. Moreover, capsaicin synergistically enhanced the cytotoxicity and cell growth inhibition of erlotinib in NSCLC cells, which were associated with the down-regulation of ERCC1 expression and inactivation of AKT in A549 and H1975 cells. Together, these results may provide a rationale to combine capsaicin with erlotinib for lung cancer treatment.

This paper describes the radio frequency (RF) measurement and tuning result of a 13 MeV Alvarez-type drift tube linac (DTL) for a compact pulsed hadron source (CPHS) at Tsinghua University. The design, machining, assembly, and alignment of the DTL are presented for integrity. The CPHS project consists of a high-current proton linac (13 MeV, 16 kW, peak current of 50 mA, 0.5 ms pulse width at 50 Hz), a neutron target station, a small-angle neutron scattering instrument, and a neutron imaging/radiology station. The linac contains an electron cyclotron resonance ion source, a low energy beam transport line, a four-vane radio frequency quadrupole (RFQ) accelerator, an Alvarez-type DTL, a high energy beam transport line, and a RF power supply and distributor. Construction on the CPHS started in June 2009, and the CPHS has provided 2000 h since 2013 to users with the neutrons produced by the 3 MeV proton beam from the radio frequency quadrupole bombarding on the beryllium target as an achievement of its mid-term objective. Presently, the tuning of the assembled DTL cavity has been completed successfully. The 4.3-m-long DTL consists of 40 accelerating cells, among which 39 full-length drift tubes (DTs) are suspended inside the cavity, and two half-length DTs are mounted inside the two end flanges of the cavity. Each DT contains a permanent magnet quadrupole. Thirteen post couplers and nine tuners are available for the tuning of the field. The relative error of the field after tuning is within ±1.6%, with a tilt sensitivity within ±33%/MHz in all cells. The beam energy will reach its designed value of 13 MeV after the DTL is installed in the beam line downstream the 3 MeV RFQ accelerator.

Ampelocalamuscalcareus is a climbing and slender bamboo, known from south Guizhou, China. This species grows in broadleaved forests of limestone montane areas. Recent molecular phylogenetic analyses demonstrated that A.calcareus was sister to all other lineages of the tribe Arundinarieae rather than a member of Ampelocalamus . The morphological features and habitats of A.calcareus and related genera including Ampelocalamus , Drepanostachyum and Himalayacalamus were compared and discussed. The characteristics of the branch complements, nodes and foliage leaves distinguish A.calcareus from morphologically similar taxa. On the basis of molecular and morphological evidence, we propose to establish a new genus, Hsuehochloa , to accommodate A.calcareus and to honour the late Chinese bamboo taxonomist Chi-Ju Hsueh (Ji-Ru Xue). In addition, we describe the inflorescence of Hsuehochloa for the first time.

Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects that include anti-cancer and anti-inflammatory properties. Xeroderma pigmentosum complementation group C (XPC) protein is an important DNA damage recognition factor in nucleotide excision repair and is involved in regulating non-small cell lung cancer (NSCLC) cell proliferation and viability. Erlotinib (Tarceva R ) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated clinical activity in NSCLC cells. However, whether astaxanthin and erlotinib could induce synergistic cytotoxicity in NSCLC cells through modulating XPC expression is unknown. In this study, we found that p38 MAPK activation by astaxanthin decreased XPC expression in two human lung adenocarcinoma A549 and H1975 cells. Inactivation of p38 MAPK by pharmacological inhibitor SB203580 or the specific small interfering RNA (siRNA) rescued the astaxanthin-reduced XPC mRNA and protein levels. Enforced expression of XPC cDNA or inhibiting the p38 MAPK activity reduced the cytotoxicity and cell growth inhibition of astaxanthin. In contrast, knockdown of XPC using siRNA enhanced the cytotoxic effects of astaxanthin. Moreover, astaxanthin synergistically enhanced cytotoxicity and cell growth inhibition of erlotinib in NSCLC cells, which were associated with the down-regulation of XPC expression and activation of p38 MAPK. Our findings suggested that the astaxanthin induced p38 MAPK mediated XPC down-regulation enhanced the erlotinib-induced cytotoxicity in A549 and H1975 cells.

Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies, accounting for about 3% of all gastrointestinal tumors. GATA5 is a transcription factor capable of suppressing the development of various human cancer types. Transcriptional inactivation and CpG island (CGI) methylation of GATA3 and GATA5, two members of the GATA family of transcription factors, have been observed in some human cancers. But whether high-density CGI methylation of GATA5 is associated with the clinical course of CCA patients has not been clarified. Herein, we observed reduced expression of GATA5 in CCA tissues compared with noncancerous tissues. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored GATA5 expression in CCA cell lines. Furthermore, GATA5 expression was downregulated after treatment with IL-6 in human intrahepatic biliary epithelial cells. Upregulated GATA5 inhibited CCA cell growth and metastasis. Mechanistically, GATA5 suppressed CCA cell growth and metastasis via Wnt/β-catenin pathway. Specific β-catenin inhibitor or siRNA abolished the discrepancy of the proliferation and metastasis capacity between GATA5-overexpression CCA cells and their control cells, which further confirmed that Wnt/β-catenin was required in GATA5-inhibited CCA cell growth and metastasis., (Copyright © 2018. Published by Elsevier Inc.)

Background/aims: A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson's disease (PD)., Methods: PubMed, Embase and the Cochrane Library were searched from their establishment dates up to January 2017 for randomized controlled trials (RCTs) investigating the efficacy of the above ten drugs on the non-motor symptoms of PD. A network meta-analysis combined the evidence from direct comparisons and indirect comparisons and evaluated the pooled weighted mean difference (WMD) values and surfaces under the cumulative ranking curves (SUCRA). The network meta-analysis included 21 RCTs., Results: The analysis results indicated that, using the United Parkinson's Disease Rating Scale (UPDRS) III, the efficacies of placebo, ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole and levodopa in treating PD were lower than that of apomorphine (WMD = -10.90, 95% CI = -16.12∼-5.48; WMD = -11.85, 95% CI = -17.31∼-6.16; WMD = -11.15, 95% CI = -16.64∼-5.04; WMD = -11.70, 95% CI = -16.98∼-5.60; WMD = -11.04, 95% CI = -16.97∼-5.34; WMD = -13.27, 95% CI = -19.22∼-7.40; WMD = -10.25, 95% CI = -15.66∼-4.32; and WMD = -11.60, 95% CI = -17.89∼-5.57, respectively). Treatment with ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil or levodopa, with placebo as a control, on PD exhibited no significant differences on PD symptoms when the UPDRS II was used for evaluation. Moreover, using the UPDRS III, the SUCRA values indicated that a pomorphine had the best efficacy on the non-motor symptoms of PD (99.0%). Using the UPDRS II, the SUCRA values for ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil and levodopa treatments, with placebo as a control, indicated that bromocriptine showed the best efficacy on the non-motor symptoms of PD (75.6%)., Conclusion: Among ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, apomorphine may be the most efficacious drug for therapy in treating the non-motor symptoms of PD., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Etoposide (VP16) is a topoisomerase II inhibitor and has been used for the treatment of non-small cell lung cancer (NSCLC). Xeroderma pigmentosum complementation group C (XPC) protein is a DNA damage recognition factor in nucleotide excision repair and involved in regulating NSCLC cell proliferation and viability. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. In this study, we report whether Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) enhanced etoposide-induced cytotoxicity in NSCLC cells through modulating the XPC expression. We found that etoposide increased XPC expression in an AKT activation manner in 2 squamous cell carcinoma H1703 and H520 cells. Knockdown of XPC using siRNA or inactivation of AKT by pharmacological inhibitor PI3K inhibitor (LY294002) enhanced the cytotoxic effects of etoposide. In contrast, enforced expression of XPC cDNA or AKT-CA (a constitutively active form of AKT) reduced the cytotoxicity and cell growth inhibition of etoposide. Hsp90 inhibitor 17-AAG enhanced cytotoxicity and cell growth inhibition of etoposide in NSCLC cells, which were associated with the downregulation of XPC expression and inactivation of AKT. Our findings suggested that the Hsp90 inhibition induced XPC downregulation involved in enhancing the etoposide-induced cytotoxicity in H1703 and H520 cells., (© 2018 S. Karger AG, Basel.)

Background: Heterogeneous rates of molecular evolution are universal across the tree of life, posing challenges for phylogenetic inference. The temperate woody bamboos (tribe Arundinarieae, Poaceae) are noted for their extremely slow molecular evolutionary rates, supposedly caused by their mysterious monocarpic reproduction. However, the correlation between substitution rates and flowering cycles has not been formally tested., Results: Here we present 15 newly sequenced plastid genomes of temperate woody bamboos, including the first genomes ever sequenced from Madagascar representatives. A data matrix of 46 plastid genomes representing all 12 lineages of Arundinarieae was assembled for phylogenetic and molecular evolutionary analyses. We conducted phylogenetic analyses using different sequences (e.g., coding and noncoding) combined with different data partitioning schemes, revealing conflicting relationships involving internodes among several lineages. A great difference in branch lengths were observed among the major lineages, and topological inconsistency could be attributed to long-branch attraction (LBA). Using clock model-fitting by maximum likelihood and Bayesian approaches, we furthermore demonstrated extensive rate variation among these major lineages. Rate accelerations mainly occurred for the isolated lineages with limited species diversification, totaling 11 rate shifts during the tribe's evolution. Using linear regression analysis, we found a negative correlation between rates of molecular evolution and flowering cycles for Arundinarieae, notwithstanding that the correlation maybe insignificant when taking the phylogenetic structure into account., Conclusions: Using the temperate woody bamboos as an example, we found further evidence that rate heterogeneity is universal in plants, suggesting that this will pose a challenge for phylogenetic reconstruction of bamboos. The bamboos with longer flowering cycles tend to evolve more slowly than those with shorter flowering cycles, in accordance with a putative generation time effect.

Background: The Cornales is the basal lineage of the asterids, the largest angiosperm clade. Phylogenetic relationships within the order were previously not fully resolved. Fifteen plastid genomes representing 14 species, ten genera and seven families of Cornales were newly sequenced for comparative analyses of genome features, evolution, and phylogenomics based on different partitioning schemes and filtering strategies., Results: All plastomes of the 14 Cornales species had the typical quadripartite structure with a genome size ranging from 156,567 bp to 158,715 bp, which included two inverted repeats (25,859-26,451 bp) separated by a large single-copy region (86,089-87,835 bp) and a small single-copy region (18,250-18,856 bp) region. These plastomes encoded the same set of 114 unique genes including 31 transfer RNA, 4 ribosomal RNA and 79 coding genes, with an identical gene order across all examined Cornales species. Two genes (rpl22 and ycf15) contained premature stop codons in seven and five species respectively. The phylogenetic relationships among all sampled species were fully resolved with maximum support. Different filtering strategies (none, light and strict) of sequence alignment did not have an effect on these relationships. The topology recovered from coding and noncoding data sets was the same as for the whole plastome, regardless of filtering strategy. Moreover, mutational hotspots and highly informative regions were identified., Conclusions: Phylogenetic relationships among families and intergeneric relationships within family of Cornales were well resolved. Different filtering strategies and partitioning schemes do not influence the relationships. Plastid genomes have great potential to resolve deep phylogenetic relationships of plants.

Background & Aims: Macrophages play vital roles in chronic liver injury, and have been tested as a tool for cytotherapy in liver fibrosis. However, macrophages possess ontogenic and functional heterogeneities. Some subsets are pro-fibrotic, whereas others are anti-fibrotic. This study aimed to clarify which macrophage subset is efficient for cytotherapy in liver fibrosis and to elucidate the underlying mechanisms., Methods: Liver fibrosis was induced in mice by carbon tetrachloride injection or bile duct ligation. Bone-marrow-derived macrophages (BMDMs) were polarized into M0, M1, or M2 macrophages, respectively. BMDMs were infused into mice through the tail vein at different stages of fibrogenesis. Fibrosis progression, hepatic cell populations, and related molecular changes were evaluated., Results: Both M0 and M1 BMDMs significantly ameliorated liver fibrosis, but M1 exhibited stronger therapeutic effects than M0. M2 macrophages were not effective on liver fibrosis. M1 macrophages reduced the number and activation of hepatic stellate cells (HSCs), which could be attributed at least partly to increased HSC apoptosis. M1 macrophages enhanced the recruitment of endogenous macrophages into fibrotic liver, which displayed the phenotype of Ly6C lo restorative macrophages and produced matrix metalloproteinases (MMPs) and hepatic growth factor (HGF) to enhance collagen degradation and hepatocyte proliferation, respectively. M1 macrophages also increased the number of total and activated natural killer (NK) cells in the fibrotic liver, which released TNF-related apoptosis-inducing ligand (TRAIL), inducing HSC apoptosis., Conclusions: M1 macrophages, which modulate the immune microenvironment to recruit and modify the activation of endogenous macrophages and NK cells, are effective for cytotherapy in experimental liver fibrosis. Lay summary: M1 Bone marrow-derived macrophages (BMDMs) exhibit a stronger therapeutic effect by modulating the hepatic microenvironment to recruit and modify the activation of endogenous macrophages and natural killer (NK) cells, which likely lead to hepatic stellate cells (HSCs) apoptosis and hampered fibrogenesis., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Few studies have comparatively assessed differences in the incidence of childhood cancer by race and ethnicity that could inform etiologic research. We aimed to identify disparities in the incidence of pediatric extracranial embryonal tumors by race and ethnicity in the United States using a population-based cancer registry., Methods: Cases of extracranial embryonal tumors among children age 0 to 19 years diagnosed between 2000 and 2010 were retrieved from the Surveillance, Epidemiology, and End Results Program 18 (n = 8188). Age-standardized incidence rates and incidence rate ratios (IRRs) were obtained by race/ethnicity. Whites were the reference group. The percentage of families living below the poverty line by county was used to stratify by socioeconomic status (SES)., Results: All minority groups had a lower incidence of neuroblastoma (Hispanics: IRR = 0.53, 95% confidence interval [CI] = 0.47 to 0.59; blacks: IRR = 0.70, 95% CI = 0.61 to 0.81; Native-Hawaiian/Asian-Pacific-Islander (API): IRR = 0.56, 95% CI = 0.46 to 0.67; and American Indian/Alaska Native (AI/AN): IRR = 0.28, 95% CI = 0.15 to 0.48) while Hispanics had a higher incidence of retinoblastoma (IRR = 1.26, 95% CI = 1.07 to 1.48). Incidence of nephroblastoma was lower among Hispanics (IRR = 0.80, 95% CI = 0.71 to 0.91) and API (IRR = 0.43, 95% CI = 0.33 to 0.56) while equivalent for blacks. Similarly, incidence of rhabdomyosarcoma was low among Hispanics (IRR = 0.85, 95% CI = 0.74 to 0.98) and API (IRR = 0.61, 95% CI = 0.47 to 0.79) while equivalent for blacks. However, incidence of hepatoblastoma was low among blacks (IRR = 0.44, 95% CI = 0.28 to 0.68) while equivalent for Hispanics and API. Incidence of germ cell tumors was higher among Hispanics (IRR = 1.30, 95% CI = 1.19 to 1.42) and lower among blacks (IRR = 0.52, 95% CI = 0.44 to 0.61) and API (IRR = 0.79, 95% CI = 0.67 to 0.93). No effect modification by SES was observed., Conclusions: Unique incidence patterns of childhood extracranial embryonal tumors exist by race and ethnicity in the United States. The interplay between race/ethnicity and genetics, epigenetics, and gene-environment interactions in the causation of these cancers deserves further investigation., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Gaultheria series Trichophyllae Airy Shaw is an angiosperm clade of high-alpine shrublets endemic to the Himalaya-Hengduan Mountains and characterized by recent species divergence and convergent character evolution that has until recently caused much confusion in species circumscription. Although multiple DNA sequence regions have been employed previously, phylogenetic relationships among species in the group have remained largely unresolved. Here we examined the effectiveness of the plastid genome for improving phylogenetic resolution within the G. series Trichophyllae clade. Plastid genomes of 31 samples representing all 19 recognized species of the series and three outgroup species were sequenced with Illumina Sequencing technology. Maximum likelihood (ML), maximum parsimony (MP) and Bayesian inference (BI) phylogenetic analyses were performed with various datasets, i.e., that from the whole plastid genome, coding regions, noncoding regions, large single-copy region (LSC) and inverted-repeat region a (IRa). The partitioned whole plastid genome with inverted-repeat region b (IRb) excluded was also analyzed with ML and BI. Tree topologies based on the whole plastid genome, noncoding regions, and LSC region datasets across all analyses, and that based on the partitioned dataset with ML and BI analyses, are identical and generally strongly supported. Gaultheria series Trichophyllae form a clade with three species and one variety that is sister to a clade of the remaining 16 species; the latter comprises seven main subclades. Interspecific relationships within the series are strongly supported except for those based on the coding-region and IRa-region datasets. Eight divergence hotspot regions, each possessing >5% percent variable sites, were screened across the whole plastid genome of the 28 individuals sampled in the series. Results of morphological character evolution reconstruction diagnose several clades, and a hypothesis of adaptive evolution for plant habit is postulated., (Copyright © 2017 Elsevier Inc. All rights reserved.)

MicroRNA-146a (miR-146a) is associated with human inflammatory disease, such as thyroid-associated ophthalmopathy (TAO), but its role in human T cells and relevance to TAO remains ambiguous. In this study, T cells of TAO patients showed downregulated expression of miR-146a. We characterized miR-146a in T cells and examined miR-146a as a critical inhibitor of Th1 differentiation processes. MiR-146a inhibited Th1 differentiation processes and cell proliferation of T-lymphocytes. Thus, the results showed that miR-146a was a potent inhibitor of Th1 differentiation and cell proliferation of human T cells and dysregulation of miR-146a contributed to the pathogenesis of TAO., Competing Interests: None.

The predominantly aquatic order Alismatales, which includes approximately 4,500 species within Araceae, Tofieldiaceae, and the core alismatid families, is a key group in investigating the origin and early diversification of monocots. Despite their importance, phylogenetic ambiguity regarding the root of the Alismatales tree precludes answering questions about the early evolution of the order. Here, we sequenced the first complete plastid genomes from three key families in this order:Potamogeton perfoliatus(Potamogetonaceae),Sagittaria lichuanensis(Alismataceae), andTofieldia thibetica(Tofieldiaceae). Each family possesses the typical quadripartite structure, with plastid genome sizes of 156,226, 179,007, and 155,512 bp, respectively. Among them, the plastid genome ofS. lichuanensisis the largest in monocots and the second largest in angiosperms. Like other sequenced Alismatales plastid genomes, all three families generally encode the same 113 genes with similar structure and arrangement. However, we detected 2.4 and 6 kb inversions in the plastid genomes ofSagittariaandPotamogeton, respectively. Further, we assembled a 79 plastid protein-coding gene sequence data matrix of 22 taxa that included the three newly generated plastid genomes plus 19 previously reported ones, which together represent all primary lineages of monocots and outgroups. In plastid phylogenomic analyses using maximum likelihood and Bayesian inference, we show both strong support for Acorales as sister to the remaining monocots and monophyly of Alismatales. More importantly, Tofieldiaceae was resolved as the most basal lineage within Alismatales. These results provide new insights into the evolution of Alismatales as well as the early-diverging monocots as a whole., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Tumor-associated macrophages (TAM) contribute greatly to hallmarks of cancer. Notch blockade was shown to arrest TAM differentiation, but the precise role and underlying mechanisms require elucidation. In this study, we employed a transgenic mouse model in which the Notch1 intracellular domain (NIC) is activated conditionally to define the effects of active Notch1 signaling in macrophages. NIC overexpression had no effect on TAM differentiation, but it abrogated TAM function, leading to repressed growth of transplanted tumors. Macrophage miRNA profiling identified a novel downstream mediator of Notch signaling, miR-125a, which was upregulated through an RBP-J-binding site at the first intronic enhancer of the host gene Spaca6A. miR-125a functioned downstream of Notch signaling to reciprocally influence polarization of M1 and M2 macrophages by regulating factor inhibiting hypoxia inducible factor-1α and IRF4, respectively. Notably, macrophages transfected with miR-125a mimetics increased phagocytic activity and repressed tumor growth by remodeling the immune microenvironment. We also identified a positive feedback loop for miR-125a expression mediated by RYBP and YY1. Taken together, our results showed that Notch signaling not only supported the differentiation of TAM but also antagonized their protumorigenic function through miR-125a. Targeting this miRNA may reprogram macrophages in the tumor microenvironment and restore their antitumor potential., (©2016 American Association for Cancer Research.)

In this paper we investigate the biogeography of the temperate woody bamboos (Arundinarieae) using a densely-sampled phylogenetic tree of Bambusoideae based on six plastid DNA loci, which corroborates the previously discovered 12 lineages (I-XII) and places Kuruna as sister to the Chimonocalamus clade. Biogeographic analyses revealed that the Arundinarieae diversified from an estimated 12 to 14Mya, and this was followed by rapid radiation within the lineages, particularly lineages IV, V and VI, starting from c. 7-8Mya. It is suggested that the late Miocene intensification of East Asian monsoon may have contributed to this burst of diversification. The possibilities of the extant Sri Lankan and African temperate bamboo lineages representing 'basal elements' could be excluded, indicating that there is no evidence to support the Indian or African route for migration of temperate bamboo ancestors to Asia. Radiations from eastern Asia to Africa, Sri Lanka, and to North America all are likely to have occurred during the Pliocene, to form the disjunct distribution of Arundinarieae we observe today. The two African lineages are inferred as being derived independently from Asian ancestors, either by overland migrations or long-distance dispersals. Beringian migration may explain the eastern Asian-eastern North American disjunction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Tilia is an ecologically and economically important genus in the family Malvaceae. However, there is no complete plastid genome of Tilia sequenced to date, and the taxonomy of Tilia is difficult owing to frequent hybridization and polyploidization. A well-supported interspecific relationships of this genus is not available due to limited informative sites from the commonly used molecular markers. We report here the complete plastid genome sequences of four Tilia species determined by the Illumina technology. The Tilia plastid genome is 162,653 bp to 162,796 bp in length, encoding 113 unique genes and a total number of 130 genes. The gene order and organization of the Tilia plastid genome exhibits the general structure of angiosperms and is very similar to other published plastid genomes of Malvaceae. As other long-lived tree genera, the sequence divergence among the four Tilia plastid genomes is very low. And we analyzed the nucleotide substitution patterns and the evolution of insertions and deletions in the Tilia plastid genomes. Finally, we build a phylogeny of the four sampled Tilia species with high supports using plastid phylogenomics, suggesting that it is an efficient way to resolve the phylogenetic relationships of this genus.

Mesenchymal stem cell (MSC) differentiation is dramatically reduced after long-term in vitro culture, which limits their application. MSCs derived from induced pluripotent stem cells (iPSCs-MSCs) represent a novel source of MSCs. In this study, we investigated the therapeutic effect of iPSC-MSCs on diabetic mice. Streptozocin-induced diabetic mice transplanted with 400 islets alone or with 1×10(6) iPSC-MSCs were examined following rapamycin injection (0.1 mg/kg/day, i.p., from days 0 to 9) after transplantation. Our results showed that iPSC-MSCs combined with rapamycin significantly prolonged islet allograft survival in the diabetic mice; 50% of recipients exhibited long-term survival (>100 days). Histopathological analysis revealed that iPSC-MSCs combined with rapamycin preserved the graft effectively, inhibited inflammatory cell infiltration, and resulted in substantial release of insulin. Flow cytometry results showed that the proportion of CD4(+) and CD8(+) T cells was significantly reduced, and the number of T regulatory cells increased in the spleen and lymph nodes in the iPSC-MSCs combined with the rapamycin group compared with the rapamycin-alone group. Production of the Th1 proinflammatory cytokines interleukin-2 (IL-2) and interferon-γ was reduced, and secretion of the anti-inflammatory cytokines IL-10 and transforming growth factor-β was enhanced compared with the rapamycin group, as determined using enzyme-linked immunosorbent assays. Transwell separation significantly weakened the immunosuppressive effects of iPSC-MSCs on the proliferation of Con A-treated splenic T cells, which indicated that the combined treatment exerted immunosuppressive effects through cell-cell contact and regulation of cytokine production. Taken together, these findings highlight the potential application of iPSC-MSCs in islet transplantation.