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Early events in the evolution of an ancestral lineage can shape the adaptive patterns of descendant species, but the evolutionary mechanisms driving initial adaptation from an ancestor remain largely unexplored. High‐altitude adaptations have been extensively explored from the viewpoint of protein‐coding genes; however, the contribution of noncoding regions remains relatively neglected. Here, we integrate genomic and transcriptomic data to investigate adaptive evolution in the ancestor of three high‐altitude snowfinch species endemic to the Qinghai–Tibet Plateau. Our genome‐wide scan for adaptation in the snowfinch ancestor identifies strong adaptation signals in functions of development and metabolism for the coding genes, but in functions of the nervous system development for noncoding regions. This pattern is exclusive to the snowfinch ancestor compared to a control ancestral lineage subject to weak selection. Changes in noncoding regions in the snowfinch ancestor, especially those nearest to coding genes, may be disproportionately associated with the differential expression of genes in the brain tissue compared to other tissues. Extensive gene expression in the brain tissue can be further altered via genetic regulatory networks of transcription factors harbouring potential accelerated regulatory regions (e.g., the development‐related transcription factor YEATS4). Altogether, our study provides new evidence concerning how coding and noncoding sequences work through decoupled pathways in initial adaptation to the selective pressure of high‐altitude environments. The analysis highlights the idea that noncoding sequences may be promising elements in facilitating the rapid evolution and adaptation to high altitudes. [ABSTRACT FROM AUTHOR]

Environmental pollution can result in poor sperm quality either directly or indirectly in birds. However, adaptive and compensatory sperm morphology changes and motility improvements have rapidly evolved in tree sparrows (Passer montanus) inhabiting polluted areas over the past 65 years. To identify the genetic underpinnings of the rapidly evolving sperm phenotype, we carried out population genomics and transcriptomics on tree sparrow populations in the two differently polluted places. We identified a gene encoding the serine/threonine protein kinase PIM1, which may drive rapid phenotypic evolution of sperm. An unprecedented and remarkable expansion of the PIM gene family, caused by tandem and segmental duplication of PIM1, was subsequently observed in the tree sparrow genome. Most PIM1 duplicates showed a testis‐specific expression pattern, suggesting that their functions are related to male reproduction. Furthermore, the elevated expression level of PIM1 was consistent with our earlier findings of longer and faster swimming sperm in polluted sites, indicating an important role for duplicated PIM1 in facilitating the rapid evolution of sperm. Our results suggest that duplicated PIM1 provides sources of genetic variation that may enable the rapid evolution of sperm under environmental heavy metal pollution. The findings of this study indicated that duplicated genes can be targets of selection and predominant sources for rapid adaptation to environmental change and shed light on sperm evolution under pollution stress. [ABSTRACT FROM AUTHOR]

As a reactive hydrogen species, the hydrogen radical (H⋅) scarcely sees applications in tumor biological therapy due to the very limited bio‐friendly sources of H⋅. In this work, we report that TAF can act as an organic photosensitizer as well as an efficient photocatalytic H⋅ generator with reduced glutathione (GSH) as a fuel. The photoactivation of TAF leads to cell death in two ways including triple amplification of oxidative stress via ferroptosis‐apoptosis under normoxia and apoptosis through biological reductions under hypoxia. TAF presents excellent biosafety with ultrahigh photocytotoxicity index at an order of magnitude of 102–103 on both normoxic and hypoxic cells. The in vitro data suggest that H⋅ therapy is promising to overcome the challenge of tumor hypoxia at low doses of both photocatalyst and light. In addition, the capability of near‐infrared two‐photon excitation would benefit broad biological applications. [ABSTRACT FROM AUTHOR]

The seasonal migration of birds is a fascinating natural wonder. Avian migratory behaviour changes are common and are probably a polygenic process as avian migration is governed by multiple correlated components with a variable genetic basis. However, the genetic and phenotypic changes involving migration changes are poorly studied. Using one annotated near‐chromosomal level de novo genome assembly, 50 resequenced genomes, hundreds of morphometric data and species distribution information, we investigated population structure and genomic and phenotypic differences associated with differences in migratory behaviour in a songbird species, Yellow‐throated Bunting Emberiza elegans (Aves: Emberizidae). Population genomic analyses reveal extensive gene flow between the southern resident and the northern migratory populations of this species. The hand‐wing index is significantly lower in the resident populations than in the migratory populations, indicating reduced flight efficiency of the resident populations. Here, we discuss the possibility that nonmigratory populations may have originated from migratory populations though migration loss. We further infer that the alterations of genes related to energy metabolism, nervous system and circadian rhythm may have played major roles in regulating migration change. Our study sheds light on phenotypic and polygenic changes involving migration change. [ABSTRACT FROM AUTHOR]

Morphology has been a leading taxonomic guiding light to systematists for the last couple of hundred years. However, the genetic and – more recently – genomic revolution have produced numerous demonstrations of erroneous classifications that were based on labile morphological traits. We used thousands of genome‐wide markers to shed light on evolutionary dynamics in a confusing and taxonomically obscure group of Asian Cyornis flycatchers. Using genomic data, we corroborated recent findings based on three mitochrondrial and five nuclear genes that the two taxa hainanus and klossi which were previously treated as separate species (Cyornis hainanus and Cyornis rubeculoides klossi, respectively) are genomically homogeneous and form a single species, C. hainanus. We also uncovered a novel case of interbreeding between C. hainanus and a non‐sister species, C. glaucicomans, illustrating these flycatchers' ability to hybridise in marginal situations even after substantial times of divergence. Our study illustrates how genome‐wide loci can shed light on complicated taxonomic problems, resulting in a better integration of phenotypic and genotypic data. [ABSTRACT FROM AUTHOR]

The controlled intracellular release of nitrite is still an unmet challenge due to the lack of bio‐friendly donors, and the antitumor effect of nitrite is limited by its physiologically inert activity. Herein, we designed benzothiadiazole‐based organic nitrite donors that are stable against bio‐relevant species but selectively respond to dithiol species through SNAr/intramolecular cyclization tandem reactions in the aqueous media. The bioorthogonal system was established to target the endoplasmic reticulum (ER) of liver cancer HepG2 cells. The nitrite and nonivamide were coupled to induce elevation of intracellular levels of calcium ions as well as reactive oxygen/nitrogen species, which resulted in ER stress and mitochondrial dysfunction. We demonstrated that a combination of photoactivation and "click to release" strategy could enhance antitumor effect in cellular level and show good potential for cancer precision therapy. [ABSTRACT FROM AUTHOR]

Aim: Species living in a shared environment face similar selective pressures and often evolve adaptive divergence to avoid competition. Quantifying phenotypic divergence and its genetic parallelism among sympatric species is important for understanding of ecologically moderated biodiversity. Here, we integrate ecologic, phenotypic and genomic datasets to study to what extent three sympatrically snowfinches (Montifringilla adamsi, Pyrgilauda ruficollis and Onychostruthus taczanowskii) differ in their adaptations in order to co‐exist in a shared environment. Location: Qinghai–Tibetan Plateau. Methods: We used principal component analysis to summarize and compare environmental and phenotypic divergence. We compared phenotypes relevant to body and beak sizes (n = 68) because they are indicators of niche and food segregation, thus critical for establishing co‐existence of sympatric birds. We used comparative genomics (n = 33) to identify genetic loci that are highly divergent between species as well as loci unique for each of species. Using vector analyses, we integrated correlation and permutation to quantify parallelism between phenotypic and genetic divergences. Results: We found that body and beak sizes are significantly different among three snowfinches. The phenotypic differentiations are greater in species that share similar ecological conditions than in those that do not. We showed that genes related to developmental process are over‐represented within highly divergent genomic regions and unique genetic loci of each species. We found that the extent of phenotypic divergence between snowfinch pairs is more strongly correlated with the magnitude of divergence in developmental genes than in the whole genome. Main conclusions: Adaptive divergence of sympatric snowfinches is highly constrained on developmental genes. As this genetic divergence is strongly correlated with divergence of the traits related to segregation in niche and food resources, this correlation reflects either causal effects or indirect consequences of ecological mediated changes. Our study provides novel insights into the mechanisms underlying evolutionary versatility and ecological success among sympatric species. [ABSTRACT FROM AUTHOR]

Pectoralis phenotypic variation plays a fundamental role in locomotion and thermogenesis in highland birds. However, its regulatory and metabolic mechanisms remain enigmatic to date. Here, we integrated phenomic, transcriptomic, and metabolomic approaches to determine muscle variation and its underpinning mechanisms across altitudinal songbirds. Phenomics confirmed that all highland birds had considerable increases in muscle oxidative capacity, capillarity, and mitochondrial abundance in our study. Correspondingly, transcriptomic analyses found that differentially expressed genes in phenotype‐associated modules enriched for blood vessel, muscle structure development, and mitochondrial organization. Despite similar traits and functional enrichments across highland birds, different mechanisms drove their occurrence in high‐altitude tree sparrow and 2 snow finches. Importantly, a metabolic feature shared by all the 3 highland birds is the improvement in insulin sensitivity and glucose utilization through activating insulin signaling pathway, which is vital to increase muscle oxidative capacity and maintain metabolic homeostasis. Nevertheless, fatty acid biosynthesis and oxidation are enhanced in only 2 snow finches which had a long evolutionary history on the high plateau, also differing from ketone body metabolism in recently introduced colonizer of the tree sparrow of the high plateau. Our study represents a vital contribution to reveal the regulatory and metabolic basis of pectoralis variation across altitudinal songbirds. [ABSTRACT FROM AUTHOR]

Environment‐responsive in situ synthesis of molecular fluorescent dyes is challenging. Herein, we develop a photoextension strategy to make trimethine cyanines with decent conversion efficiency (up to 81 %) using 1‐butyl 2,3,3‐trimethyl 3H‐indole derivatives as the sole precursors, and demonstrate a free radical mechanism. In the inducer‐extension stage, free radicals and reactive oxygen species (ROS) were able to mediate similar reactions with no assistance of light. We explored a Mito‐extension strategy to in situ synthesize trimethine cyanines in the living cells. The cellular ROS‐dependence provided a foundation for preferential cyanine expression in cancer cells. Finally, we applied an iodized precursor as an intrinsic ROS‐activated theranostic agent that integrated mitochondria‐targeted cyanine synthesis, cell imaging and phototherapy. [ABSTRACT FROM AUTHOR]

Gene therapy has attracted great attention due to its applications in disease treatment. The key point for gene therapy is how to improve the efficiency of gene delivery and precisely control gene expression. Conjugated polymers (CPs) have hydrophobic π‐conjugated backbones and modifiable side chains, which provide desired photophysical properties and have been applied in the field of bio‐sensing, biomedical and gene‐based therapies. Herein, we summarize the strategies of DNA delivery and small interfering RNA (siRNA) delivery based on cationic conjugated polymers, in addition, the strategies for precisely control the expression of target gene by photothermal‐responsive conjugated polymers for cancer therapy and gene editing are described. Finally, future challenges of efficient and safe gene delivery strategies are presented, and perspectives in the precise control of gene expression are also discussed. [ABSTRACT FROM AUTHOR]

A new gas hydrate reservoir stimulation method of in‐situ fracturing with transient heating is proposed, in line with analysis of the technological bottlenecks faced by marine gas hydrate production. This method injects the developed chemical reagents into a hydrate reservoir through hydraulic fracturing, releasing heat during the chemical reaction to increase the hydrate decomposition rate. The chemical reaction product furthermore has a honeycomb structure to support fractures and increase reservoir permeability. Based on the geological model of natural gas hydrate in the South China Sea, three development methods are simulated to evaluate hydrate production capacity, consisting of horizontal well, fractured horizontal well and in‐situ fracturing with transient heating well. Compared with the horizontal well, the simulation results show that the cumulative gas production of the fractured horizontal well in one year is 7 times that of the horizontal well, while the cumulative gas production of in‐situ fracturing with transient heating well is 12 times that of the horizontal well, which significantly improves daily efficiency and cumulative gas production. In addition, the variation patterns of hydrate saturation and temperature‐pressure fields with production time for the three exploitation plans are presented, it being found that three sensitive parameters of fracture conductivity, fracture half‐length and fracture number are positively correlated with hydrate production enhancement. Through the simulations, basic data and theoretical support for the optimization of gas hydrate reservoir stimulation scheme has been provided. [ABSTRACT FROM AUTHOR]

Inside living cells, regulation of catalytic activity of artificial enzymes remains challenging due to issues such as biocompatibility, efficiency, and stability of the catalyst, by which the practical applications of artificial enzymes have been severely hindered. Here, an artificial enzyme, PTT‐SGH, with responsiveness to reactive oxygen species (ROS), was obtained by introducing a catalytic histidine residue to pentaerythritol tetra(3‐mercaptopropionate) (PTT). The artificial enzyme formed large aggregates in cells via the intracellular ROS‐mediated oxidation of thiol groups. The process was significantly facilitated in tumor cells because of the higher ROS concentration in the tumor microenvironment. The catalytic activity of this artificial enzyme was intensively enhanced through deprotonation of cross‐linked PTT‐SGH, which showed typical esterase activities. Selective fluorescence imaging of tumor cells was achieved using the artificial enzyme to trigger the cleavage of the ester bond of the caged fluorophore inside living cells. [ABSTRACT FROM AUTHOR]

The ozonosphere is infiltrated by UV‐A rays (λ = 320–400 nm) that reach the Earth's atmosphere, posing serious health problems such as premature aging and skin cancer. Owing to the importance of UV‐A ray detection, highly detective, novel, and high‐speed UV‐A photodetectors have recently attracted considerable attention. The integration of organic and inorganic hybrid structures yields highly attractive optoelectronic properties that make them attractive candidates for high‐performance self‐powered UV‐A photodetectors. Herein, the integration of conductive polypyrrole (Ppy) and GaN nanorods for high‐performance self‐powered UV‐A photodetectors is demonstrated. The device exhibits superior photoresponse properties such as detectivity, responsivity, and external quantum efficiency values as 5.0 × 1012 Jones, 102 A W−1, and 29.8 × 103%, respectively, at a power density of 1.32 mW cm−2 (λ = 382 nm) and zero bias, which are relatively higher than those of pristine GaN nanorods. Furthermore, the device exhibits good stability and reproducibility with fast rising (350 ms) and falling (410 ms) times. The high photoresponse is attributed to the large built‐in potential formed at the interface junction of the Ppy and the GaN nanorods. Furthermore, the mechanism behind the high photoresponse is investigated using an X‐ray photoelectron spectroscopy (XPS) analysis and energy band theory. [ABSTRACT FROM AUTHOR]

This study explores the evolutionary history of ecological niche characters in the Eurasian snowfinch lineage. Specifically, we use new analytical approaches to reconstruct ecological niche evolution, taking into account uncertainty in knowledge of the ecological niche limits. We found an overall pattern of niche conservatism in relation to both temperature and precipitation characteristics of niches, but for one dramatic niche evolution event, in Montifringilla nivalis. Interestingly, this species is also that which has the broadest geographic distribution among snowfinches. We conclude that an evolutionary change in niche characteristics perhaps within M. nivalis (i.e. present in some and not all of its populations) made possible the broad, westward range expansion of that species, thus changing dramatically the distributional potential of the snowfinch lineage. [ABSTRACT FROM AUTHOR]

Inspired by the human skin, electronic skins (e-skins) composed of various flexible sensors, such as strain sensor, pressure sensor, shear force sensor, temperature sensor, and humility sensor, and delicate circuits, are emerged to mimic the sensing functions of human skins. In this review, the strategies to realize the versatile functionalities of natural skin-like e-skins, including strain-, pressure-, shear force-, temperature-and humility-sensing abilities, as well as self-healing ability and other functions are summarized. Some representative examples of high-performance e-skins and their applications are outlined and discussed. Finally, the outlook of the future of e-skins is presented. [ABSTRACT FROM AUTHOR]

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Photoactivated trimerization of 2,3,3‐trimethyl‐3H‐indole derivatives created near infrared fluorophore Cy5. The synthetic method is air‐tolerant, photosensitizer free, metal free, and condensation agent free. Living cells make Cy5 on a time scale of minutes under white light irradiation at a low power intensity, with the monomer as the only exogenous agent. The new method is promising to find applications in cell studies for in situ spatiotemporally controlled fluorescence imaging in living cells. [ABSTRACT FROM AUTHOR]

Aim: The Pleistocene glacial cycles play a prominent role in shaping phylogeographical patterns of organisms, while few studies have focused on the regional difference of glacial effects. By acquiring comprehensive knowledge of the origin, diversification and historical demography of an intensively studied passerine species complex, Great Tit, we aim to test the regional variation of the Late Pleistocene glaciation impacts on this widely distributed bird lineage. Location: Eurasia and associated peninsulas and archipelagos. Taxa: Parus major species complex. Methods: Phylogeny, divergence times and demographic dynamics were estimated with Bayesian methods. Population structure, genetic diversity and correlation between genetic and physical distances were estimated based on mtDNA variation. Glacial‐to‐present distributional changes were assessed via ecological niche modelling (ENM). Results: Five major clades (Central Asia, Eastern Asia, Eastern Himalaya, Northern and Western Eurasia and Southern Asia) were detected, with divergence times ranging 1.57–0.50 million years ago. Genetic diversity values and Bayesian skyline plots suggest that the three eastern clades had a deeper population history. A more complex geographic structure was observed in East Asia. Demographic expansion during the last glacial cycle was indicated for all five clades. ENM results showed broad conservatism of traits related to climate tolerances, and generally broader and more continuous distributional patterns under glacial conditions. Main Conclusions: The Great Tit complex probably originated in Southeast Asia. Geographic barriers, such as the deserts of Central Asia and the Qinghai–Tibet Plateau appear to be related to the lineage divergence. Late Pleistocene climate cycles influenced both demographic dynamics and divergence, especially in terms of east–west differences in relation to geographic complexity. [ABSTRACT FROM AUTHOR]

Aim: To document the species richness patterns of breeding birds along elevational gradients and explore its drivers in the Horn of Africa region. Location: Horn of Africa region. Taxon: Breeding birds. Methods: Distributional data for breeding birds were collected. Elevational distribution data were extracted, interpolated, and assembled for all birds, passerines, and nonpasserines. In order to tease apart how different environmental factors contributed to the variation in species richness, we found it is necessary to divide the area into four subregions with different climatic regimes and topographic structure, namely western slope, eastern slope, wet side, and dry side. Then, the species richness in each 100‐m elevational band was counted along the elevational gradients of each subregion. Pearson's correlation analyses and ordinary least squares (OLS) regressions were used to examine the relationships between species richness and factors. Results: The variation in species richness followed hump‐shaped patterns for all subregions, although with peak values at different elevations. The bird species groups on the western and eastern slopes showed low and high plateaus with mid‐elevation peaks, respectively, but very low species diversities at the highest elevations. Species richness was significantly correlated with temperature range and productivity in each subregion. The temperature range, area, and productivity explained 82% of the species richness variations for all birds on the western slope. Main conclusions: The separate analyses of four area subdivisions provide strong indications of how various factors interact. Productivity and temperature range were the major driving factors for shaping the richness patterns, but deviations from expected patterns suggest modifying roles of mist formation zones in the valleys that deeply intersect the large highlands in the west and rich riparian vegetation where water from cool and humid environments at high elevation reaches lower elevations in the arid east. Conservation is recommended in each subregion based on the elevational richness scenarios. [ABSTRACT FROM AUTHOR]

Summary: To investigate the effects of Lactobacillus casei on Chinese sauerkraut fermentation, L. casei 11MZ‐5‐1 was inoculated into Chinese sauerkraut. Physicochemical indexes were measured, and the microbial dynamics during the fermentation were analysed by quantitative real‐time PCR (qRT‐PCR) and polymerase chain reaction‐denaturing gradient gel electrophoresis (PCR‐DGGE). The result showed that inoculation with L. casei 11MZ‐5‐1 lowered the pH of the fermentation system more rapidly than in the control model (CK). The content of vitamin C (VC) (44.64 ± 2.12 mg kg−1) was higher and nitrite (under 0.76 mg kg−1) was lower than CK (P < 0.05). The numbers of 16S rRNA gene copies in the experimental model (BA) were lower than in CK at the end fermentation time. According to the PCR‐DGGE analyses, 22 and 17 specific bands were detected in CK and BA, respectively. L. paracasei and L. casei were predominant during the fermentation in BA. The relative abundance and diversity indices of bacteria in BA were 8.23 ± 0.25 and 2.01 ± 0.06, respectively, lower than in the CK (P < 0.05). So, the L. casei 11MZ‐5‐1 inoculations could effectively inhibit the microbial diversity in the fermentation system. The fermented cabbage with L. casei 11MZ‐5‐1 was more favourably estimated by consumers in terms of colour, crispness, sourness, aroma, bitterness, stink, stale flavour and overall acceptability. [ABSTRACT FROM AUTHOR]

Abstract: Recently, artificially structured metamaterials (MMs) are proposed to manipulate the wave propagation behaviors in single physical domain. However, the multiphysics manipulation is rarely reported and remains a challenging issue to be investigated. Here, the design of MMs with simultaneous controls of acoustic and electromagnetic (EM) waves is presented. A double‐membrane structure is proposed to meet the need of acoustic‐wave insulation, and patterned anisotropic meta‐atoms on the membrane are employed to generate polarization‐dependent functions of EM waves. The designed structure is validated numerically and experimentally, suggesting a new route for joint modulations of acoustic and EM waves in the engineering. [ABSTRACT FROM AUTHOR]

Abstract: Corilagin is a component of Phyllanthus urinaria extract and has been found of possessing anti‐inflammatory, anti‐oxidative, and anti‐tumour properties in clinic treatments. However, the underlying mechanisms in anti‐cancer particularly of its induction of cell death in human breast cancer remain undefined. Our research found that corilagin‐induced apoptotic and autophagic cell death depending on reactive oxygen species (ROS) in human breast cancer cell, and it occurred in human breast cancer cell (MCF‐7) only comparing with normal cells. The expression of procaspase‐8, procaspase‐3, PARP, Bcl‐2 and procaspase‐9 was down‐regulated while caspase‐8, cleaved PARP, caspase‐9 and Bax were up‐regulated after corilagin treatment, indicating apoptosis mediated by extrinsic and mitochondrial pathways occurred in MCF‐7 cell. Meanwhile, autophagy mediated by suppressing Akt/mTOR/p70S6K pathway was detected with an increase in autophagic vacuoles and LC3‐II conversion. More significantly, inhibition of autophagy by chloroquine diphosphate salt (CQ) remarkably enhanced apoptosis, while the caspase inhibitor z‐VAD‐fmk failed in affecting autophagy, suggesting that corilagin‐induced autophagy functioned as a survival mechanism in MCF‐7 cells. In addition, corilagin induced intracellular reactive oxygen species (ROS) generation, when reduced by ROS scavenger NAC, apoptosis and autophagy were both down‐regulated. Nevertheless, in SK‐BR3 cell which expressed RIP3, necroptosis inhibitor Nec‐1 could not alleviate cell death induced by corilagin, indicating necroptosis was not triggered. Subcutaneous tumour growth in nude mice was attenuated by corilagin, consisting with the results in vitro. These results imply that corilagin inhibits cancer cell proliferation through inducing apoptosis and autophagy which regulated by ROS release. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The Sino‐Himalayas have higher species richness than adjacent regions, making them a global biodiversity hotspot. Various mechanisms, including ecological constraints, energetic constraints, diversification rate (DivRate) variation, time‐for‐speciation effect and multiple colonizations, have been posited to explain this pattern. We used pheasants (Aves: Phasianidae) as a model group to test these hypotheses and to understand the ecological and evolutionary processes that have generated the extraordinary diversity in these mountains. Location: Sino‐Himalayas and adjacent regions. Taxon: Pheasants. Methods: Using distribution maps predicted by species distribution models (SDMs) and a time‐calibrated phylogeny for pheasants, we examined the relationships between species richness and predictors including net primary productivity (NPP), niche diversity (NicheDiv), DivRate, evolutionary time (EvolTime) and colonization frequency using Pearson's correlations and structural equation modelling (SEM). We reconstructed ancestral ranges at nodes and examined basal/derived species patterns to reveal the mechanisms underlying species richness gradients in the Sino‐Himalayas. Results: We found that ancestral pheasants originated in Africa in the early Oligocene (~33 Ma), and then colonized the Sino‐Himalayan mountains and other regions. In the Sino‐Himalayas, species richness was strongly related to DivRate, NPP, NicheDiv and colonization frequency, but weakly correlated with EvolTime. The direct effects of NicheDiv and DivRate on richness were stronger than NPP and EvolTime. NPP indirectly influenced species richness via DivRate, but its effect on richness via NicheDiv was relatively weak. Main conclusions: Higher species diversity in the Sino‐Himalayas was generated by both ecological and evolutionary mechanisms. An increase in available niches, rapid diversifications and multiple colonizations was found to be key direct processes for the build‐up of the diversity hotspots of pheasants in the Sino‐Himalayan mountains. Productivity had an important but indirect effect on species richness, which worked through increased DivRate. Our study offers new insights on species accumulation in the Sino‐Himalayas and provides a useful model for understanding other biodiversity hotspots. [ABSTRACT FROM AUTHOR]

A series of novel uranyl coordination polymers have been synthesized by hydrothermal reactions. Both complexes 1 and 2 prosess two ipbp− ligands (H2ipbpCl=1-(3,5-dicarboxyphenyl)-4,4′-bipyridinium chloride), one uranyl cation, and two coordination water molecules, which can further extend to 2D networks through hydrogen bonding. In complex 1, two sets of equivalent nets are entangled together, resulting in a 2D + 2D → 3D polycatenated framework. In complex 2, the neighbouring equivalent nets interpenetrate each other, forming a twofold interpenetrated network. Complexes 3 and 4 are isomers, and both of them are constructed from (UO2)2(OH)2 dinuclear units, which are connected with four ipbp− ligands. The 3D structures of complexes 3 and 4 are similar along the b axis. Similar to other viologen-based coordination polymers, complexes 3 and 4 exhibit photochromic and thermochromic properties, which are rarely observed in actinide coordination polymers. Unlike the monotonous coordination mode in complexes 1- 4, the ipbp− ligands feature a μ3-bridge through two kinds of coordination modes in complex 5. Notably, complex 5 presents a unique example in which terminal pyridine nitrogen atom is involved in the coordination. [ABSTRACT FROM AUTHOR]

Patterns of heterogeneous genomic differentiation have been well documented between closely related species, with some highly differentiated genomic regions ('genomic differentiation islands') spread throughout the genome. Differential levels of gene flow are proposed to account for this pattern, as genomic differentiation islands are suggested to be resistant to gene flow. Recent studies have also suggested that genomic differentiation islands could be explained by linked selection acting on genomic regions with low recombination rates. Here, we investigate genomic differentiation and gene-flow patterns for autosomes using RAD-seq data between two closely related species of long-tailed tits ( Aegithalos bonvaloti and A. fuliginosus) in both allopatric and contact zone populations. The results confirm recent or ongoing gene flow between these two species. However, there is little evidence that the genomic regions that were found to be highly differentiated between the contact zone populations are resistant to gene flow, suggesting that differential levels of gene flow is not the cause of the heterogeneous genomic differentiation. Linked selection may be the cause of genomic differentiation islands between the allopatric populations with no or very limited gene flow, but this could not account for the heterogeneous genomic differentiation between the contact zone populations, which show evidence of recent or ongoing gene flow. [ABSTRACT FROM AUTHOR]

Aim The location of zoogeographical boundaries in eastern China has long been the subject of debate. To identify any north/south genetic divergence between the Palaearctic and Sino-Japanese realms proposed by previous studies, we conducted a comparative phylogeographical study involving three passerine species with wide latitudinal distributions in eastern China. Location Eastern China. Methods Two mitochondrial genes and three nuclear introns were amplified and sequenced. Population structures were analysed using intra-specific phylogeny, tcs networks, AMOVA and structure inferences. We tested for evidence of genetic barriers based on pairwise differences. Lineage divergences, demographic dynamics and gene flow between lineages were estimated using Bayesian methods. Results A congruent north/south phylogeographical divergence was identified for three species. A geographical barrier was inferred at c. 40° N in eastern China. The population sizes of the northern and southern lineages have both been stable through the late Pleistocene, while multiple divergences were inferred during the early and middle Pleistocene. Main conclusions Our results suggest a general phylogeographical break in north-eastern China, coinciding with the Palaearctic/Sino-Japanese boundary. Physical blocking of the Yan Mountains and fragmentation of suitable habitat during glacial stages between the north and south probably acted together to provide long-lasting barrier effects. Our comparative phylogeographical approach demonstrates that the Palaearctic/Sino-Japanese boundary may represent a gene-flow barrier even within widespread species. [ABSTRACT FROM AUTHOR]

Eurasia is a large continent characterized by heterogeneous environments. Glacial cycles during the late Pleistocene have had variable impacts on the avifauna across Eurasia. Bird populations from South-East Asia show stability through the Last Glacial Maximum ( LGM), while populations from Europe exhibit evidence of post- LGM expansion. We investigated the phylogeography of the Long-tailed Tit ( Aegithalos caudatus), which spans the longitudinal breadth of Eurasia to test how climatic history and regional topographical complexity affected populations and diversification within the species complex. Our results show that two lineages from central and southern China (lineages C and D) segregate geographically, while lineages across northern Eurasia (lineage A and B) show substantial sympatry. Bayesian estimates for the timing of diversification suggest that the four lineages diverged during the middle Pleistocene, splitting in parallel and undergoing concurrent demographic histories since divergence. A. caudatus lineages experienced similar and synchronous population size dynamics during glacial cycles before the LGM. We conclude that the difference in geo-topologic complexity may be an important factor that led to the variation in secondary admixture between northern Eurasian and eastern Asian lineages. [ABSTRACT FROM AUTHOR]

Despite extensive studies on the multifaceted roles of morroniside, the main active constituent of iridoid glycoside from Corni Fructus, the effect of morroniside on osteoarthritis ( OA) chondrocytes remains poorly understood. Here, we investigated the influence of morroniside on cultured human OA chondrocytes and a rat experimental model of OA. The results showed that morroniside enhanced the cell viability and the levels of proliferating cell nuclear antigen expression ( PCNA), type II collagen and aggrecan in human OA chondrocytes, indicating that morroniside promoted chondrocyte survival and matrix synthesis. Furthermore, different doses of morroniside activated protein kinase B ( AKT) and extracellular signal-regulated kinase ( ERK) in human OA chondrocytes, and in turn, triggered AKT/S6 and ERK/P70S6K/S6 pathway, respectively. The PI3K/ AKT inhibitor LY294002 or the MEK/ ERK inhibitor U0126 attenuated the effect of morroniside on human OA chondrocytes, indicating that the activation of AKT and ERK contributed to the regulation of morroniside in human OA chondrocytes. In addition, the intra-articular injection of morroniside elevated the level of proteoglycans in cartilage matrix and the thickness of articular cartilage in a rat experimental model of OA, with the increase of AKT and ERK activation. As a consequence, morroniside has chondroprotective effect on OA chondrocytes, and may have the therapeutic potential for OA treatment. [ABSTRACT FROM AUTHOR]

Little has been published to describe or interpret Asian biodiversity hotspots, including those in the East Himalayan Mountains of Southwest China (HMSC), thus making necessary a review of the current knowledge. The Pliocene and Pleistocene geological and glacial histories of the Asian continent differ from those of Europe and North America, suggesting different mechanisms of speciation and extinction, and, thus, different responses to climate changes during the Quaternary glaciations. This short review summarizes potential drivers in shaping and maintaining high species richness and endemism of birds in the HMSC. The geographical location at the junction of different biogeographical realms, the wide range of habitats and climates along the extensive elevational range, the complex topography and the distinct geological history of this region have probably contributed to the evolution of an exceptionally species-rich and endemic-rich, specialized montane avian fauna. The Mountain systems in the HMSC may have provided refugia where species survived during the glacial periods and barriers for preventing species dispersal after the glacial periods. More studies are required to further test this refugia hypothesis by comparing more cold-tolerent and warm-tolerent species. [ABSTRACT FROM AUTHOR]

The distribution and the contamination level of uranium (U) and thorium (Th) radionuclides and potentially toxic metals, Cu, Li, Mn, Sr, and Zn were investigated in surface sediments from aquifer systems around a uranium industrial site in the northern Guangdong Province, China. Total contents of these elements and other major elements, including Fe, Al, Mg, Na, Ca, and K, were analyzed by inductively coupled plasma optical emission spectrometry. The results show that the contents of U, Th, Cu, and Mn are elevated in the sediments from a recipient stream that drains the industrial site and the reservoir downstream. Metal contents varied significantly among the sampling locations, and generally displayed a decreasing trend as the distance from the U industrial site increased. However, the highest level of U, Th, Cu, and Mn is observed in the terminal of the recipient stream, where is the inlet of a reservoir. Assessment of elemental enrichment in the sediments using enrichment factor and geoaccumulation index indicates that among the analyzed metals, U, Th, and Cu are the major contaminants, while contaminations of Li, Mn, Sr, and Zn which displayed depletion to minimal enrichment are not significant. [ABSTRACT FROM AUTHOR]

Aim East Asia is known for its exceptionally high biological diversity and endemism. Various geological and climatic events during the Pliocene and Pleistocene have been invoked to explain this high endemism, and these processes have had different impacts on different organisms. Herein, we investigate the relative role of these historical processes in the genetic evidence for endemism of intraspecific lineages of two East Asian species: the grey-cheeked fulvetta ( Alcippe morrisonia) and the red-headed tree babbler ( Stachyridopsis ruficeps). Location East Asia. Methods We studied the genetic structure based on mitochondrial and nuclear DNA and evaluated the phylogeographical lineages using coalescent species tree approaches. The influences of different historical processes on diversification among phylogeographical lineages were analysed using coalescent models. We tested correlations between ecological divergence and phylogeographical splits. Results The genetic structure analysis and species tree estimation revealed three deeply divergent lineages within both species. One lineage is endemic to the mountains of Southwest China and the other to Taiwan. Coalescent simulations suggested that lineage diversification mostly occurred during the late Pliocene. Within this time frame, uplift of the mountains of Southwest China and formation of the island of Taiwan are geological events consistent with the geographical isolation and ecological niche divergence of these phylogeographical lineages. Main conclusions Our results suggest that the main driver of avian endemism in East Asia was the formation of new montane and island habitats following the uplift of the mountains of Southwest China and formation of the island of Taiwan in the Pliocene. However, the populations in the two regions were affected differently by the climatic oscillations during the Pleistocene. The mountains of Southwest China were climatically stable during glaciations, allowing populations to persist throughout the Pleistocene and maintain their genetic uniqueness. In contrast, glaciations resulted in lowered sea levels, allowing dispersal between the island of Taiwan and mainland China, thus obscuring the genetic endemism of the Taiwanese populations. [ABSTRACT FROM AUTHOR]

Aim To understand the causes of historical and current elevational richness patterns of Leiothrichinae babblers, a diverse and mostly endemic group of birds. Location A 5000-m elevational gradient in the Hengduan Mountains, China. Methods By means of a dated phylogenetic tree and reconstructed ancestral states, we estimated elevation-specific diversification rate, applied a new method to estimate colonization frequency and age and, for the first time, modelled historical species richness patterns that take account of temporal patterns of palaeotemperature. As explanations for current richness patterns, we assessed area, geometric constraints, temperature, precipitation, seasonality and productivity. Results The current elevational pattern of species richness is a hump-shaped curve with a peak at about 1000-2500 m. The reconstructed palaeopatterns of species richness suggest that babblers, as a clade, first occupied the Hengduan Mountains at low to mid-elevations, although the method of ancestral state reconstruction cannot conclusively reject origins outside the current elevational distribution of the group. Diversification rates varied little along the elevational gradient, and thus cannot explain the richness pattern, but historical colonization frequency and colonization age were highly correlated with present-day species richness. Seasonality and productivity had greater power than area and geometric constraints in explaining the present-day richness pattern of babblers along the elevational gradient. Conclusions Historical and modern factors have both played important roles in shaping species richness patterns. Reconstructed historical richness patterns suggest that babblers first diversified in the Hengduan Mountains at low to mid elevations, but richness patterns almost certainly shifted substantially under changing climates of the past 10 Myr. The current richness patterns of babblers are associated with seasonality and productivity, but they are also a product of historical evolutionary and ecological dynamics. The methods we introduce for assessing historical colonization rates and past patterns of richness offer promise for understanding other elevational richness gradients. [ABSTRACT FROM AUTHOR]

China's Southwest Mountainous Region in Eastern Himalaya is a 'biodiversity hotspot' of global interest for conservation. Yet little is known about what has driven this unique diversity. The dramatic topography of the Southwest Mountainous Region resulting from the tectonic uplift during the late Pliocene leads to dramatic ecological stratification, which creates physical barriers to migration and isolates organisms into different subregions and mountain systems. This agrees with the observation that the phylogeographical patterns found in four species of birds ( Alcippe morrisonia, Stachyridopsis ruficeps, Parus monticolus and Aegithalos concinnus) distributed in this region are characterized by deep splits between lineages that coalesce between 0.8 and 2.1 Ma. Unlike other regions at this latitude, the Southwest Mountainous Region was largely unaffected by the Pleistocene glaciations. Genetically isolated populations of these birds could thus be maintained throughout the Pleistocene in these rather stable montane environments. In comparison, we found radically different phylogeographical patterns in populations of the same four species distributed in the adjacent lowland, the Central China region. This region has a distinctly different geological history with dramatic, climate-induced shifts in vegetation during the Pleistocene. Here, we found a considerably less geographical structure in the genetic variation and a much younger coalescence time (0.3-0.7 Ma). We also found evidence of genetic bottlenecks during the glacial periods and gene flow during the interglacial expansions. We conclude that the high genetic diversity in the Southwest Mountainous Region results from a long-term in situ diversification within these evolutionary isolated and environment stable montane habitats. [ABSTRACT FROM AUTHOR]

As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine has been recently reported to exhibit anti-tumour effects against a wide spectrum of cancer. However, the mechanism was largely unknown. Gene chip array reveals that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down-regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling. TOPflash analysis revealed that Wnt activity was significantly reduced after berberine treatment, and the mechanism of which might be that berberine disrupted β-catenin transfer to nucleus through up-regulating the expression of adenomatous polyposis coli (APC) gene and stabilized APC-β-catenin complex. Berberine administration in ApcMin/+ mice exhibited fewer and smaller polyps in intestine, along with reduction in cyclin D1 and c-Myc expression. In clinical practice, oral administration of berberine also significantly reduced the familial adenomatous polyposis patients' polyp size along with the inhibition of cyclin D1 expression in polyp samples. These observations indicate that berberine inhibits colon tumour formation through inhibition of Wnt/β-catenin signalling and berberine might be a promising drug for the prevention of colon cancer. [ABSTRACT FROM AUTHOR]

Mangiferin is the main bioactive component in mango leaves, which possesses anti-inflammatory, antioxidative, antidiabetic, immunomodulatory, and antitumor activities. In the present study, a microwave-assisted extraction method was developed for the extraction of mangiferin from mango leaves. Some parameters such as ethanol concentration, liquid-to-solid ratio, microwave power, and extraction time were optimized by single-factor experiments and response surface methodology. The optimal extraction conditions were 45% ethanol, liquid-to-solid ratio of 30:1 (mL/g), and extraction time of 123 s under microwave irradiation of 474 W. Under optimal conditions, the yield of mangiferin was 36.10 ± 0.72 mg/g, significantly higher than that of conventional extraction. The results obtained are beneficial for the full utilization of mango leaves and also indicate that microwave-assisted extraction is a very useful method for extracting mangiferin from plant materials. [ABSTRACT FROM AUTHOR]

Aim Two alternative genetic patterns are typical in recently established populations. One is reduced genetic diversity but significant population structuring compared with original populations. The other is the persistence of genetic polymorphisms and the lack of differentiation in frontier populations. This study aims to test for these patterns by examining population genetics of the Light-vented Bulbul ( Pycnonotus sinensis), an Oriental bird that has been undergoing rapid range expansion. Location Eastern China. Methods Molecular analyses were conducted on mitochondrial DNA and microsatellite datasets from 256 individuals. Intraspecific phylogeny was reconstructed by Bayesian inference and network analysis. Analysis of molecular variance ( AMOVA) and Bayesian clustering were applied to determine population structure. Genetic diversity was tested to determine whether there were significant differences between frontier and source populations. Population expansions were tested in mt DNA and microsatellites. Gene flow and recent migrants were estimated by Bayesian methods. Results Both high- and low-nucleotide diversities were recorded in frontier populations, and differences in genetic diversity between frontier and source populations were not statistically significant. Population differentiation was recorded in some source but not in frontier populations. Population size expansion was detected both in frontier and in source populations, and for the whole dataset, commencing before the Last Glacial Maximum. Main conclusions Genetic diversity can be maintained in expanding populations of the Light-vented Bulbul, and genetic differentiation can be avoided, where substantial genetic exchanges are occurring. This study also discusses the potential effects of evolutionary properties such as historical population growth on recently recorded range expansion. [ABSTRACT FROM AUTHOR]

Aim We combined genetic sequence data and ecological niche modelling to resolve the impacts of past climatic fluctuations on the distribution, genetic diversification, and demographic dynamics of an East Asian montane bird, the green-backed tit ( Parus monticolus). Location East Asia. Methods Phylogenetic analyses were carried out using four mitochondrial fragments and seven nuclear loci from 161 birds sampled from 29 localities spanning the entire geographical range of the green-backed tit. We used * beast to estimate the species tree and calculate divergence times. Extended Bayesian skyline plots were used to infer potential historical shifts in population size. We used MaxEnt to predict potential distributions during three periods: the present day, the Last Glacial Maximum and the Last Interglacial. Results The mitochondrial DNA (mt DNA) gene tree showed strong support for three reciprocally monophyletic groups: a south-western clade, a central clade and a Taiwanese clade. Taiwanese and Vietnamese samples had fixed differences at several nuclear loci, but the south-western and central samples shared haplotypes at all nuclear loci. The mt DNA gene tree topology differed from the species tree topology. The species tree suggested sister relationships between Taiwanese and Vietnamese operational taxonomic units ( OTUs) and between south-western and central OTUs. Diversification within the green-backed tit was relatively recent, probably within the last 0.9 million years. Extended Bayesian skyline plots suggested rapid population expansion in the south-western and central phylogroups after the Last Interglacial, and this result was consistent with ecological niche models. Main conclusions Our results suggest that genetic diversification within the green-backed tit was affected by the later Pleistocene climate fluctuations. Ecological niche models indicated that the present-day vegetation distribution was, in many ways, more similar to that of the Last Glacial Maximum than it was to that of the Last Interglacial. Continental populations of the green-backed tit experienced unusual demographic and range expansion that is likely to have occurred during the cooling transition between the Last Interglacial and the Last Glacial Maximum. We found incongruence between the mt DNA gene tree and the species tree, which underscores the importance of using both mitochondrial and nuclear markers when estimating the evolutionary history of populations. [ABSTRACT FROM AUTHOR]

Although Pleistocene glaciations had a major impact on the population genetic patterns of many species in North America and Europe, it remains unclear how these climatic fluctuations contributed to species diversification in East Asia. One reason for this is the difficulty of distinguishing genetic admixture following secondary contact from incomplete lineage sorting, both of which can generate similar patterns of genetic variation. Using a combination of multilocus analyses and coalescent simulation, we explore how these two processes occurred in the Pleistocene evolutionary history of a widespread East Asian bird, the Vinous-throated parrotbill, Paradoxornis webbianus. Maximum likelihood ( ML) tree identified two major mitochondrial lineages, which are geographically separated in most parts of its range, but are sympatric at a few sampling sites. NJ tree and Structure analysis of microsatellite data set revealed an extensive level of admixture and little population structure, suggesting recent admixture between two formerly separated groups. Networks from nuclear DNA data sets, however, did not indicate any geographically isolated groups but rather a panmictic population, thus support incomplete lineage sorting. By using coalescent simulation approaches, we show that both processes did occur, although at different temporal scales. During the Pleistocene glaciations, probably around 0.1-0.5 Ma (the Marine Isotope Stage 6, MIS6), P. webbianus contracted into two separate refugia, and subsequently accumulated genetic divergence. During the interglacial MIS5, the species expanded into previously glaciated areas allowing the once separated groups to come into contact and become admixed. Taken together, our results indicate the current genetic variation within P. webbianus is a combination pattern of widespread distribution in pre- Pleistocene, then contraction and fragmentation into separated refugia during glacial advance, followed by recently postglacial expansion and admixture. [ABSTRACT FROM AUTHOR]

The northern region of Guangdong Province, China, has suffered from the extensive mining/milling of uranium for several decades. In this study, surface waters in the region were analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES) for the concentrations of uranium (U), thorium (Th), and non-radioactive metals (Fe, Mn, Mg, Li, Co, Cu, Ni, and Zn). Results showed highly elevated concentrations of the studied radionuclides and metals in the discharged effluents and the tailing seepage of the U mining/milling sites. Radionuclide and heavy metal concentrations were also observed to be overall enhanced in the recipient stream that collected the discharged effluents from the industrial site, compared to the control streams, and rivers with no impacts from the U mining/milling sites. They displayed significant spatial variations and a general decrease downstream away from upper point-source discharges of the industrial site. In addition, obvious positive correlations were found between U and Th, Fe, Zn, Li, and Co ( R2 > 0.93, n = 28) in the studied water samples, which suggest for an identical source and transport pathway of these elements. In combination with present surface water chemistry and chemical compositions of uraniferous minerals, the elevation of the analyzed elements in the recipient stream most likely arose from the liquid effluents, processing water, and acid drainage from the U mining/milling facilities. The dispersion of radionuclides and hazardous metals is actually limited to a small area at present, but some potential risk should not be negligible for local ecosystem. The results indicate that environmental remediation work is required to implement and future cleaner production technology should be oriented to avoid wide dispersion of radioactivity and non-radioactive hazards in U mining/milling sites. [ABSTRACT FROM AUTHOR]

Different scales and frequencies of glaciations developed in Europe and Asia during the Pleistocene. Because species' responses to climate change are influenced by interactive factors including ecology and local topography, the pattern and tempo of species diversification may vary significantly across regions. The great tit Parus major is a widespread Eurasian passerine with a range that encircles the central Asian desert and high-altitude areas of the Tibetan Plateau. A number of genetic studies have assessed the effect of paleo-climate changes on the distribution of the European population. However, none have comprehensively addressed how paleo-climate change affected the distribution of the great tit in China, an apparent hotspot of P. major subspecific diversity. Here, we describe likely paleo-climatic effects on P. major populations in China based on a combination of phylogeography and ecological niche models (ENMs). We sequenced three mitochondrial DNA markers from 28 populations (213 individuals), and downloaded 112 sequences from outside its Chinese range. As the first step in clarifying the intra-specific relationships among haplotypes, we attempted to clarify the divergence and demography of populations in China. Phylogeographic analysis revealed that P. major is comprised of five highly divergent clades with geographic breaks corresponding to steep mountains and dry deserts. A previously undescribed monophyletic clade with high genetic diversity, stable niches and a long and independent evolutionary history was detected in the mountainous areas of southwest China. The estimated times at which these clades diverged was traced back to the Early-Middle Pleistocene (2.19-0.61 mya). Contrary to the post-LGM (the Last Glacial Maximum) expansion of European populations, demographic history indicates that Asian populations expanded before the LGM after which they remained relatively stable or grew slowly through the LGM. ENMs support this conclusion and predict a similar distribution in the present and the LGM. Our genetic and ecological results demonstrate that Pleistocene climate changes shaped the divergence and demography of P. major in China. [ABSTRACT FROM AUTHOR]

Compound K (20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, CK), an intestinal bacterial metabolite of panaxoside, has been shown to inhibit tumour growth in a variety of tumours. However, the mechanisms involved are largely unknown. We use human gastric carcinoma cell lines BGC823, SGC7901 and human gastric carcinoma xenograft in nude mice as models to study the mechanisms of CK in gastric cancers. We found that CK significantly inhibits the viabilities of BGC823 and SGC7901 cells in dose- and time-dependent manners. CK-induced BGC823 and SGC7901 cells apoptosis and cell cycle arrest in G2 phase by up-regulation of p21 and down-regulation of cdc2 and cyclin B1. Further studies show that CK induces apoptosis in BGC823 and SGC7901 cells mainly through mitochondria-mediated internal pathway, and that CK induces the translocation of nuclear Bid to mitochondria. Finally, we found that CK effectively inhibited the tumour formation of SGC7901 cells in nude mice. Our studies show that CK can inhibit the viabilities and induce apoptosis of human gastric carcinoma cells via Bid-mediated mitochondrial pathway. [ABSTRACT FROM AUTHOR]

A computational framework is described that was developed for quantitative analysis of hyperpolarized helium-3 MR lung ventilation image data. This computational framework was applied to a study consisting of 55 subjects (47 asthmatic and eight normal). Each subject was imaged before and after respiratory challenge and also underwent spirometry. Approximately 1600 image features were calculated from the lungs in each image. Both the image and 27 spirometric features were ranked based on their ability to characterize clinical diagnosis using a mutual information-based feature subset selection algorithm. It was found that the top image features perform much better compared with the current clinical gold-standard spirometric values when considered individually. Interestingly, it was also found that spirometric values are relatively orthogonal to these image feature values in terms of informational content. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Genistein is a major isoflavonoid in dietary soybean, commonly consumed in Asia. Genistein exerts inhibitory effects on the proliferation of various cancer cells and plays an important role in cancer prevention. However, the molecular and cellular mechanisms of genistein on human ovarian cancer cells are still little known. We show that exposure of human ovarian cancer HO-8910 cells to genistein induces DNA damage, and triggers G2/M phase arrest and apoptosis. Furthermore, we also found that checkpoint proteins ATM and ATR are phosphorylated and activated in the cells treated with genistein. It is also shown that genistein increases the phosphorylation and activation of Chk1 and Chk2, which results in the phosphorylation and inactivation of phosphatases Cdc25C and Cdc25A, and thereby the phosphorylation and inactivation of Cdc2 which arrests cells in G2/M phase. Moreover, genistein enhances the phosphorylation and activation of p53, while decreases the ratio of Bcl-2/Bax and Bcl-xL/Bax and the level of phosphorylated Akt, which result in cells undergoing apoptosis. These results demonstrate that genistein-activated ATM-Chk2-Cdc25 and ATR-Chk1-Cdc25 DNA damage checkpoint pathways can arrest ovarian cancer cells in G2/M phase, and induce apoptosis while the cellular DNA damage is too serious to be repaired. Thus, the antiproliferative, DNA damage-inducing and pro-apoptotic activities of genistein are probably responsible for its genotoxic effects on human ovarian cancer HO-8910 cells. [Copyright &y& Elsevier]

Osteopontin (OPN) is a secreted, integrin-binding matrix phosphorylated glycoprotein that is overexpressed in many advanced cancers. However, the functional mechanisms by which OPN contributes to the development of ovarian cancer are poorly understood. Here, we reveal that acquired expression of OPN by HO-8910 ovarian cancer cells greatly promoted the progression of ovarian cancer. OPN expression dramatically increased the colony formation of ovarian cancer cells in vitro and tumor growth in vivo. Under the stress induced by serum depletion or curcumin treatment, OPN expression promoted the survival of ovarian cells through preventing stress-induced apoptosis. At the molecular level, both endogenous and exogenous OPN expression activated the PI3-K/Akt survival pathway and dramatically decreased p53 expression under serum depletion. In addition, HIF-1α was induced in OPN-producing cells under normoxia. Furthermore, we also found that inhibition of the PI3-K/Akt pathway attenuated OPN-mediated HIF-1α up-regulation in ovarian cancer cells. Taken together, these results indicate that OPN can increase the survival of ovarian cancer cells under stress conditions in vitro and promote the late progression of ovarian cancer in vivo, and the survival-promoting functions of OPN are mediated through Akt activation and the induction of HIF-1α expression. ( Cancer Sci 2008; 99: 1901–1907) [ABSTRACT FROM AUTHOR]