ABCC4 suppresses glioblastoma progression and recurrence by restraining cGMP-PKG signalling.

BACKGROUND: Cyclic nucleotides are critical mediators of cellular signalling in glioblastoma. However, the clinical relevance and mechanisms of regulating cyclic nucleotides in glioblastoma progression and recurrence have yet to be thoroughly explored. METHODS: In silico, mRNA, and protein level analyses identified the primary regulator of cyclic nucleotides in recurrent human glioblastoma. Lentiviral and pharmacological manipulations examined the functional impact of cyclic nucleotide signalling in human glioma cell lines and primary glioblastoma cells. An orthotopic xenograft mice model coupled with aspirin hydrogels verified the in vivo outcome of targeting cyclic nucleotide signalling. RESULTS: Elevated intracellular levels of cGMP, instead of cAMP, due to a lower substrate efflux from ATP-binding cassette sub-family C member 4 (ABCC4) is engaged in the recurrence of glioblastoma. ABCC4 gene expression is negatively associated with recurrence and overall survival outcomes in glioblastoma specimens. ABCC4 loss-of-function activates cGMP-PKG signalling, promoting malignancy in glioblastoma cells and xenografts. Hydrogels loaded with aspirin, inhibiting glioblastoma progression partly by upregulating ABCC4 expressions, augment the efficacy of standard-of-care therapies in orthotopic glioblastoma xenografts. CONCLUSION: ABCC4, repressing the cGMP-PKG signalling pathway, is a tumour suppressor in glioblastoma progression and recurrence. Aspirin hydrogels impede glioblastoma progression through ABCC4 restoration and constitute a viable translational approach.

Bottom-Up Synthesis of Multicompartmentalized Microreactors for Continuous Flow Catalysis.

The bottom-up assembly of biomimetic multicompartmentalized microreactors for use in continuous flow catalysis remains a grand challenge because of the structural instability or the absence of liquid microenvironments to host biocatalysts in the existing systems. Here, we address this challenge using a strategy that combines stepwise Pickering emulsification with interface-confined cross-linking. Our strategy allows for the fabrication of robust multicompartmentalized liquid-containing microreactors (MLMs), whose interior architectures can be exquisitely tuned in a bottom-up fashion. With this strategy, enzymes and metal catalysts can be separately confined in distinct subcompartments of MLMs for processing biocatalysis or chemo-enzymatic cascade reactions. As exemplified by the enzyme-catalyzed kinetic resolution of racemic alcohols, our systems exhibit a durability of 2000 h with 99% enantioselectivity. Another Pd-enzyme-cocatalyzed dynamic kinetic resolution of amines further demonstrates the versatility and long-term operational stability of our MLMs in continuous flow cascade catalysis. This study opens up a new way to design efficient biomimetic multicompartmental microreactors for practical applications.

Hypoxia-induced CXC chemokine ligand 14 expression drives protumorigenic effects through activation of insulin-like growth factor-1 receptor signaling in glioblastoma.

Hypoxic tumor microenvironment (HTM) promotes a more aggressive and malignant state in glioblastoma. However, little is known about the role and mechanism of CXC chemokine ligand 14 (CXCL14) in HTM-mediated glioblastoma progression. In this study, we report that CXCL14 expression correlated with poor outcomes, tumor grade, and hypoxia-inducible factor (HIF) expression in patients with glioblastoma. CXCL14 was upregulated in tumor cells within the hypoxic areas of glioblastoma. Hypoxia induced HIF-dependent expression of CXCL14, which promoted glioblastoma tumorigenicity and invasiveness in vitro and in vivo. Moreover, CXCL14 gain-of-function in glioblastoma cells activated insulin-like growth factor-1 receptor (IGF-1R) signal transduction to regulate the growth, invasiveness, and neurosphere formation of glioblastoma. Finally, systemic delivery of CXCL14 siRNA nanoparticles (NPs) with polysorbate 80 coating significantly suppressed tumor growth in vivo and extended the survival time in patient-derived glioblastoma xenografts. Together, these findings suggest that HIF-dependent CXCL14 expression contributes to HTM-promoted glioblastoma tumorigenicity and invasiveness through activation of the IGF-1R signaling pathway. CXCL14 siRNA NPs as an oligonucleotide drug can inhibit glioblastoma progression and constitute a translational path for the clinical treatment of glioblastoma patients.

Potential millennial-scale avian declines by humans in southern China.

Mounting observational records demonstrate human-caused faunal decline in recent decades, while accumulating archaeological evidence suggests an early biodiversity impact of human activities during the Holocene. A fundamental question arises concerning whether modern wildlife population declines began during early human disturbance. Here, we performed a population genomic analysis of six common forest birds in East Asia to address this question. For five of them, demographic history inference based on 25-33 genomes of each species revealed dramatic population declines by 4- to 48-fold over millennia (e.g. 2000-5000 thousand years ago). Nevertheless, summary statistics detected nonsignificant correlations between these population size trajectories and Holocene temperature variations, and ecological niche models explicitly predicted extensive range persistence during the Holocene, implying limited demographic consequence of Holocene climate change. Further analyses suggest high negative correlations between the reconstructed population declines and human disturbance intensities and indicate a potential driver of human activities. These findings provide a deep-time and large-scale insight into the recently recognized avifaunal decline and support an early origin hypothesis of human effects on biodiversity. Overall, our study sheds light on the current biodiversity crisis in the context of long-term human-environment interactions and offers a multi-evidential framework for quantitatively assessing the ecological consequences of human disturbance.

Biocontrol potential of Burkholderia sp. BV6 against the rice blast fungus Magnaporthe oryzae.

AIM: To investigate the broad-spectrum antifungal activity of Burkholderia sp. BV6, that is isolated from rice roots and its biocontrol potential against rice blast caused by Magnaporthe oryzae. METHODS AND RESULTS: We evaluated the ability to isolate BV6 in the biological control of rice blast disease and investigated its antifungal mechanisms. BV6 strongly inhibited the hyphal growth of M. oryzae Guy11 and other plant pathogenic fungi, and pot experiments showed that BV6 significantly decreases the disease index of rice blast from 47.5 to 24.6. The secreted small-molecule secondary metabolites were regarded as weapons during the antifungal process by inhibiting the germination of M. oryzae conidia and mycelial growth, and thereby prevent the following infection. Liquid chromatography-mass spectrometry analysis of the metabolites from the supernatant of isolate BV6 showed that the antifungal weapons of isolate BV6 are novel, small, molecular hydrophilic compounds that are different from reported antifungal compounds. CONCLUSIONS: The isolate BV6 inhibits the M. oryzae infection by the production of small-molecule antifungal compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: The current study discovers the role of the Burkholderia sp. BV6 in the biocontrol of plant pathogenic fungi. Therefore, isolate BV6 is a potential candidate for developing a microbial formulation for the biocontrol of the most common disease of rice blast.

Synthesis, antifungal activity and 3D-QSAR study of novel acyl thiourea compounds containing gem-dimethylcyclopropane ring.

A series of novel acyl thiourea compounds containing gem-dimethylcyclopropane ring were designed and synthesized by multi-step reactions in search of novel antifungal molecules. Structures of all the target compounds were characterized by spectral techniques of UV-vis, FT-IR, 1H-NMR, 13C-NMR, and ESI-MS. The antifungal activity of the target compounds was preliminarily evaluated by agar dilution method. The antifungal bioassay revealed that, at 50 µg/mL, compounds 5h (R = o-F), 5m (R = p-Br), and 5n (R = o-NO2) showed the same antifungal activity of 73.6% against Physalospora piricola, which was comparable than that of the positive control. Furthermore, against Gibberella zeae, compounds 5k (R = m-Cl), 5l (R = m-Br), 5m (R = p-Br), and 5n (R = o-NO2) displayed the same antifungal activity of 75.6%, and compound 5o (R = p-NO2) displayed antifungal activity of 78.8%, which were all better than that of the positive control. The preliminary analysis of 3D-QSAR model was performed to study the effect of molecular structure on biological activity using the comparative molecular field analysis (CoMFA) method. The results showed 3D-QSAR model (r2 = 0.995, q2 = 0.503) was reasonable and effective.

Genetic mechanism of adaptive evolution: the example of adaptation to high altitudes.

Since Darwin's time, elucidating the mechanism of adaptive evolution has been one of the most important scientific issues in evolutionary biology and ecology. Adaptive evolution usually means that species evolve special phenotypic traits to increase fitness under selective pressures. Phenotypic adaptation can be observed at different hierarchical levels of morphology, physiology, biochemistry, histology, and behavior. With the breakthroughs of molecular biology and next-generation sequencing technologies, mounting evidence has uncovered the genetic architecture driving adaptive complex phenotypes. Studying the molecular genetic mechanisms of evolutionary adaption will enable us to understand the forces shaping biodiversity and set up genotype-phenotype-environment interactions. Genetic bases of adaptive evolution have been explained by multiple hypotheses, including major-effect genes, supergenes, polygenicity, noncoding regions, repeated regions, and introgression. The strong selection pressure exerted by high-altitude extreme environments greatly promotes the occurrence of phenotypic and genetic adaptation in species. Studies on multi-omics data provide new insights into adaptive evolution. In this review, we systematically summarize the genetic mechanism of adaptive evolution, research progress in adaptation to high-altitude environmental conditions, and existing challenges and discuss the future perspectives, thereby providing guidance for researchers in this field.

Population genomic, climatic and anthropogenic evidence suggest the role of human forces in endangerment of green peafowl (Pavo muticus).

Both anthropogenic impacts and historical climate change could contribute to population decline and species extinction, but their relative importance is still unclear. Emerging approaches based on genomic, climatic and anthropogenic data provide a promising analytical framework to address this question. This study applied such an integrative approach to examine potential drivers for the endangerment of the green peafowl (Pavo muticus). Several demographic reconstructions based on population genomes congruently retrieved a drastic population declination since the mid-Holocene. Furthermore, a comparison between historical and modern genomes suggested genetic diversity decrease during the last 50 years. However, climate-based ecological niche models predicted stationary general range during these periods and imply the little impact of climate change. Further analyses suggested that human disturbance intensities were negatively correlated with the green peafowl's effective population sizes and significantly associated with its survival status (extirpation or persistence). Archaeological and historical records corroborate the critical role of humans, leaving the footprint of low genomic diversity and high inbreeding in the survival populations. This study sheds light on the potential deep-time effects of human disturbance on species endangerment and offers a multi-evidential approach in examining underlying forces for population declines.

Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China.

INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.

Molecular architecture and mechanism of the anaphase-promoting complex.

The ubiquitination of cell cycle regulatory proteins by the anaphase-promoting complex/cyclosome (APC/C) controls sister chromatid segregation, cytokinesis and the establishment of the G1 phase of the cell cycle. The APC/C is an unusually large multimeric cullin-RING ligase. Its activity is strictly dependent on regulatory coactivator subunits that promote APC/C-substrate interactions and stimulate its catalytic reaction. Because the structures of many APC/C subunits and their organization within the assembly are unknown, the molecular basis for these processes is poorly understood. Here, from a cryo-electron microscopy reconstruction of a human APC/C-coactivator-substrate complex at 7.4 Å resolution, we have determined the complete secondary structural architecture of the complex. With this information we identified protein folds for structurally uncharacterized subunits, and the definitive location of all 20 APC/C subunits within the 1.2 MDa assembly. Comparison with apo APC/C shows that the coactivator promotes a profound allosteric transition involving displacement of the cullin-RING catalytic subunits relative to the degron-recognition module of coactivator and APC10. This transition is accompanied by increased flexibility of the cullin-RING subunits and enhanced affinity for UBCH10-ubiquitin, changes which may contribute to coactivator-mediated stimulation of APC/C E3 ligase activity.

Preclinical evaluation of exemestane as a novel chemotherapy for gastric cancer.

CYP19A1/aromatase (Ar) is a prognostic biomarker of gastric cancer (GCa). Ar is a critical enzyme for converting androstenedione to oestradiol in the steroidogenesis cascade. For decades, Ar has been targeted with Ar inhibitors (ARIs) in gynaecologic malignancies; however, it is unexplored in GCa. A single-cohort tissue microarray examination was conducted to study the association between Ar expression and disease outcome in Asian patients with GCa. The results revealed that Ar was a prognostic promoter. Bioinformatics analyses conducted on a Caucasian-based cDNA microarray databank showed Ar to be positively associated with GCa prognosis for multiple clinical modalities, including surgery, 5-Fluorouracil (5-FU) for adjuvant chemotherapy, or HER2 positivity. These findings imply that targeting Ar expression exhibits a potential for fulfilling unmet medical needs. Hence, Ar-targeting compounds were tested, and the results showed that exemestane exhibited superior cancer-suppressing efficacy to other ARIs. In addition, exemestane down-regulated Ar expression. Ablating Ar abundance with short hairpin (sh)Ar could also suppress GCa cell growth, and adding 5-FU could facilitate this effect. Notably, adding oestradiol could not prevent exemestane or shAr effects, implicating a nonenzymatic mechanism of Ar in cancer growth. Regarding translational research, treatment with exemestane alone exhibited tumour suppression efficacy in a dose-dependent manner. Combining subminimal doses of 5-FU and exemestane exerted an excellent tumour suppression effect without influencing bodyweight. This study validated the therapeutic potentials of exemestane in GCa. Combination of metronomic 5-FU and exemestane for GCa therapy is recommended.

The niches of nuthatches affect their lineage evolution differently across latitude.

Ecological niche evolution can promote or hinder the differentiation of taxa and determine their distribution. Niche-mediated evolution may differ among climatic regimes, and thus, species that occur across a wide latitudinal range offer a chance to test these heterogeneous evolutionary processes. In this study, we examine (a) how many lineages have evolved across the continent-wide range of the Eurasian nuthatch (Sitta europaea), (b) whether the lineages' niches are significantly divergent or conserved and (c) how their niche evolution explains their geographic distribution. Phylogenetic reconstruction and ecological niche models (ENMs) showed that the Eurasian nuthatch contained six parapatric lineages that diverged within 2 Myr and did not share identical climatic niches. However, the niche discrepancy between these distinct lineages was relatively conserved compared with the environmental differences between their ranges and thus was unlikely to drive lineage divergence. The ENMs of southern lineages tended to cross-predict with their neighbouring lineages whereas those of northern lineages generally matched with their abutting ranges. The coalescence-based analyses revealed more stable populations for the southern lineages than the northern ones during the last glaciation cycle. In contrast to the overlapping ENMs, the smaller parapatric distribution suggests that the southern lineages might have experienced competitive exclusion to prevent them from becoming sympatric. On the other hand, the northern lineages have expanded their ranges and their current abutting distribution might have resulted from lineages adapting to different climatic conditions in allopatry. This study suggests that niche evolution may affect lineage distribution in different ways across latitude.

Characterization of a bifunctional alginate lyase as a new member of the polysaccharide lyase family 17 from a marine strain BP-2.

OBJECTIVES: Bifunctional alginate lyase can efficiently saccharify alginate biomass and prepare functional oligosaccharides of alginate. RESULTS: A new BP-2 strain that produces alginate lyase was screened and identified from rotted Sargassum. A new alginate lyase, Alg17B, belonging to the polysaccharide lyase family 17, was isolated and purified from BP-2 fermentation broth by freeze-drying, dialysis, and ion exchange chromatography. The enzymatic properties of the purified lyase were investigated. The molecular weight of Alg17B was approximately 77 kDa, its optimum reaction temperature was 40-45 °C, and its optimum reaction pH was 7.5-8.0. The enzyme was relatively stable at pH 7.0-8.0, with a temperature range of 25-35 °C, and the specific activity of the purified enzyme reached 4036 U/mg. A low Na+ concentration stimulated Alg17B enzyme activity, but Ca2+, Zn2+, and other metal ions inhibited it. Substrate specificity analysis, thin-layer chromatography, and mass spectrometry showed that Alg17B is an alginate lyase that catalyses the hydrolysis of sodium alginate, polymannuronic acid (polyM) and polyguluronic acid to produce monosaccharides and low molecular weight oligosaccharides. Alg17B is also bifunctional, exhibiting both endolytic and exolytic activities toward alginate, and has a wide substrate utilization range with a preference for polyM. CONCLUSIONS: Alg17B can be used to saccharify the main carbohydrate, alginate, in the ethanolic production of brown algae fuel as well as in preparing and researching oligosaccharides.

Synthesis and Antiproliferative Evaluation of Novel Hybrids of Dehydroabietic Acid Bearing 1,2,3-Triazole Moiety.

To discover novel potent cytotoxic diterpenoids, a series of hybrids of dehydroabietic acid containing 1,2,3-triazole moiety were designed and synthesized. The target compounds were characterized by means of FT-IR, 1H NMR, 13C NMR, ESI-MS and elemental analysis techniques. The in vitro cytotoxicity of these compounds was evaluated by standard MTT (methyl thiazolytetrazolium) assay against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), BEL-7402 (liver) human carcinoma cell lines and human normal liver cell (HL-7702). The screening results revealed that most of the hybrids showed significantly improved cytotoxicity over parent compound DHAA. Among them, [1-(3-fluorobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3c), and [1-(2-nitrobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3k) displayed better antiproliferative activity with IC50 (50% inhibitory concentration) values of 5.90 ± 0.41 and 6.25 ± 0.37 µM toward HepG2 cells compared to cisplatin, while they exhibited lower cytotoxicity against HL-7702. Therefore, the 1,2,3-triazole-hybrids could be a promising strategy for the synthesis of antitumor diterpenoids and it also proved the essential role of 1,2,3-triazole moiety of DHAA in the biological activity.

[A new polyketide from marine-derived Streptomyces sp.MDW-06].

To isolate and identify secondary metabolites of marine-derived Streptomyces sp.MDW-06,the isolations and purifications of compounds were performed by means of column chromatography over silica gel. And their structures were elucidated through the spectroscopic analysis of MS,NMR and specific rotations. The bioactivities were assayed by paper diffusion and DPPH method. From the fermentation broth of marine-derived Streptomyces sp.MDW-06,five compounds( 1-5) were isolated and identified as streptopentanoic acid( 1),germicidin A( 2),germicidin B( 3),isogermicidin A( 4),isogermicidin B( 5) and oxohygrolidin( 6),respectively. Compound 1 is a new compound. Compound 1 shows DPPH radical scavenging activity with 36. 4% at 100 mg·L~(-1).

Synthesis and Biological Evaluation of Novel Dehydroabietic Acid-Oxazolidinone Hybrids for Antitumor Properties.

Novel representatives of the important group of biologically-active, dehydroabietic acid-bearing oxazolidinone moiety were synthesized to explore more efficacious and less toxic antitumor agents. Structures of all the newly target molecules were confirmed by IR, ¹H-NMR, 13C-NMR, and HR-MS. The inhibitory activities of these compounds against different human cancer cell lines (MGC-803, CNE-2, SK-OV-3, NCI-H460) and human normal liver cell line LO2 were evaluated and compared with the commercial anticancer drug cisplatin, using standard MTT (methyl thiazolytetrazolium) assay in vitro. The pharmacological screening results revealed that most of the hybrids showed significantly improved antiproliferative activities over dehydroabietic acid and that some displayed better inhibitory activities compared to cisplatin. In particular, compound 4j exhibited promising cytotoxicity with IC50 values ranging from 3.82 to 17.76 µM against all the test cell lines and displayed very weak cytotoxicity (IC50 > 100 µM) on normal cells, showing good selectivity between normal and malignant cells. Furthermore, the action mechanism of the representative compound 4j was preliminarily investigated by Annexin-V/PI dual staining, Hoechst 33258 staining, which indicated that the compound can induce cell apoptosis in MGC-803 cells in a dose-dependent manner and arrest the cell cycle in G1 phase. Therefore, 4j may be further exploited as a novel pharmacophore model for the development of anticancer agents.

Ice age unfrozen: severe effect of the last interglacial, not glacial, climate change on East Asian avifauna.

BACKGROUND: The glacial-interglacial cycles in the Pleistocene caused repeated range expansion and contraction of species in several regions in the world. However, it remains uncertain whether such climate oscillations had similar impact on East Asian biota, despite its widely recognized importance in global biodiversity. Here we use both molecular and ecological niche profiles on 11 East Asian avian species with various elevational ranges to reveal their response to the late Pleistocene climate changes. RESULTS: The ecological niche models (ENM) consistently showed that these avian species might substantially contract their ranges to the south during the Last Interglacial period (LIG) and expanded their northern range margins through the Last Glacial Maximum (LGM), leading to the LGM ranges observed for all 11 species. Consistently, coalescent simulations based on 25-30 nuclear genes retrieved signatures of significant population growth through the last glacial period across all species studied. Climate statistics suggested that high climatic variability during the LIG and a relatively mild climate at the LGM potentially explained the historical population dynamics of these birds. CONCLUSIONS: This is the first study based on multiple species and both lines of ecological niche profiles and genetic data to characterize the unique response of East Asian biota to late Pleistocene climate. The present study highlights regional differences in the evolutionary consequence of climate change during the last glacial cycle and implies that global warming might pose a great risk to species in this region given potentially higher climatic variation in the future analogous to that during the LIG.

Synthesis and Antifungal Activity of Novel Myrtenal-Based 4-Methyl-1,2,4-triazole-thioethers.

A series of novel myrtenal derivatives bearing 1,2,4-triazole moiety were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Their structures were confirmed by using UV-vis, FTIR, NMR, and ESI-MS analysis. Antifungal activity of the target compounds was preliminarily evaluated by the in vitro method against Fusarium oxysporum f. sp. cucumerinum, Physalospora piricola, Alternaria solani, Cercospora arachidicola, and Gibberella zeae at 50 µg/mL. Compounds 6c (R = i-Pr), 6l (R = o-NO2 Bn), and 6a (R = Et) exhibited excellent antifungal activity against P. piricola with inhibition rates of 98.2%, 96.4%, and 90.7%, respectively, showing better or comparable antifungal activity than that of the commercial fungicide azoxystrobin with a 96.0% inhibition rate, which served as a positive control.

Synthesis and Biological Activity of Novel (Z)- and (E)-Verbenone Oxime Esters.

Twenty-seven (Z)- and (E)-verbenone derivatives bearing an oxime ester moiety were designed and synthesized in search of novel bioactive molecules. Their structures were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the target compounds were preliminarily evaluated. As a result, compound (E)-4n (R = ß-pyridyl) exhibited excellent antifungal activity with growth inhibition percentages of 92.2%, 80.0% and 76.3% against Alternaria solani, Physalospora piricola, and Cercospora arachidicola at 50 µg/mL, showing comparable or better antifungal activity than the commercial fungicide chlorothalonil with growth inhibition of 96.1%, 75.0% and 73.3%, respectively, and 1.7-5.5-fold more growth inhibition than its stereoisomer (Z)-4n (R = ß-pyridyl) with inhibition rates of 22.6%, 28.6% and 43.7%, respectively. In addition, seven compounds displayed significant growth inhibition activity of over 90% against the root of rape (Brassica campestris) at 100 µg/mL, exhibiting much better herbicidal activity than the commercial herbicide flumioxazin with a 63.0% growth inhibition. Among these seven compounds, compound (E)-4n (R = ß-pyridyl) inhibited growth by 92.1%, which was 1.7-fold more than its stereoisomer (Z)-4n (R = ß-pyridyl) which inhibited growth by 54.0%.

Flying high: limits to flight performance by sparrows on the Qinghai-Tibet Plateau.

Limits to flight performance at high altitude potentially reflect variable constraints deriving from the simultaneous challenges of hypobaric, hypodense and cold air. Differences in flight-related morphology and maximum lifting capacity have been well characterized for different hummingbird species across elevational gradients, but relevant within-species variation has not yet been identified in any bird species. Here we evaluate load-lifting capacity for Eurasian tree sparrow (Passer montanus) populations at three different elevations in China, and correlate maximum lifted loads with relevant anatomical features including wing shape, wing size, and heart and lung masses. Sparrows were heavier and possessed more rounded and longer wings at higher elevations; relative heart and lung masses were also greater with altitude, although relative flight muscle mass remained constant. By contrast, maximum lifting capacity relative to body weight declined over the same elevational range, while the effective wing loading in flight (i.e. the ratio of body weight and maximum lifted weight to total wing area) remained constant, suggesting aerodynamic constraints on performance in parallel with enhanced heart and lung masses to offset hypoxic challenge. Mechanical limits to take-off performance may thus be exacerbated at higher elevations, which may in turn result in behavioral differences in escape responses among populations.