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Abstract Migratory birds experience changes in their environment and diet during seasonal migrations, thus requiring interactions between diet and gut microbes. Understanding the co‐evolution of the host and gut microbiota is critical for elucidating the rapid adaptations of avian gut microbiota. However, dynamics of gut microbial adaptations concerning elevational migratory behavior, which is prevalent but understudied in montane birds remain poorly understood. We focused on the Himalayan bluetail (Tarsiger rufilatus) in the montane forests of Mt. Gongga to understand the diet–gut microbial adaptations of elevational migratory birds. Our findings indicate that elevational migratory movements can rapidly alter gut microbial composition and function within a month. There was a significant interaction between an animal‐based diet and gut microbiota across migration stages, underscoring the importance of diet in shaping microbial communities. Furthermore, the gut microbial composition of T. rufilatus may be potentially altered by high‐altitude acclimatization. An increase in fatty acid and amino acid metabolism was observed in response to low temperatures and limited resources, resulting in enhanced energy extraction and nutrient utilization. Moreover, microbial communities in distinct gut segments varied in relative abundance and responses to environmental changes. While the bird jejunum exhibited greater susceptibility to food and environmental fluctuations, there was no significant difference in metabolic capacity among gut segments. This study provides initial evidence of rapid diet–gut microbial changes in distinct gut segments of elevational migratory birds and highlights the importance of seasonal sample collection. Our findings provide a deeper understanding of the unique high‐altitude adaptation patterns of the gut microbiota for montane elevational migratory birds.

Abstract The CRISPR-Cas9 system offers substantial potential for cancer therapy by enabling precise manipulation of key genes involved in tumorigenesis and immune response. Despite its promise, the system faces critical challenges, including the preservation of cell viability post-editing and ensuring safe in vivo delivery. To address these issues, this study develops an in vivo CRISPR-Cas9 system targeting tumor-associated macrophages (TAMs). We employ bacterial protoplast-derived nanovesicles (NVs) modified with pH-responsive PEG-conjugated phospholipid derivatives and galactosamine-conjugated phospholipid derivatives tailored for TAM targeting. Utilizing plasmid-transformed E. coli protoplasts as production platforms, we successfully load NVs with two key components: a Cas9-sgRNA ribonucleoprotein targeting Pik3cg, a pivotal molecular switch of macrophage polarization, and bacterial CpG-rich DNA fragments, acting as potent TLR9 ligands. This NV-based, self-assembly approach shows promise for scalable clinical production. Our strategy remodels the tumor microenvironment by stabilizing an M1-like phenotype in TAMs, thus inhibiting tumor growth in female mice. This in vivo CRISPR-Cas9 technology opens avenues for cancer immunotherapy, overcoming challenges related to cell viability and safe, precise in vivo delivery.

Increasing nitrogen (N) input to coastal ecosystems poses a serious environmental threat. It is important to understand the responses and feedback of N removal microbial communities, particularly nitrifiers including the newly recognized complete ammonia-oxidizers (comammox), to improve aquaculture sustainability. In this study, we conducted a holistic evaluation of the functional communities responsible for nitrification by quantifying and sequencing the key functional genes of comammox Nitrospira-amoA, AOA-amoA, AOB-amoA and Nitrospira-nxrB in fish ponds with different fish feeding levels and evaluated the contribution of nitrifiers in the nitrification process through experiments of mixing pure cultures. We found that higher fish feeding dramatically increased N-related concentration, affecting the nitrifying communities. Compared to AOA and AOB, comammox Nitrospira and NOB were more sensitive to environmental changes. Unexpectedly, we detected an equivalent abundance of comammox Nitrospira and AOB and observed an increase in the proportion of clade A in comammox Nitrospira with the increase in fish feeding. Furthermore, a simplified network and shift of keystone species from NOB to comammox Nitrospira were observed in higher fish-feeding ponds. Random forest analysis suggested that the comammox Nitrospira community played a critical role in the nitrification of eutrophic aquaculture ponds (40–70 μM). Through the additional experiment of mixing nitrifying pure cultures, we found that comammox Nitrospira is the primary contributor to the nitrification process at 200 μM ammonium. These results advance our understanding of nitrifying communities and highlight the importance of comammox Nitrospira in driving nitrification in eutrophic aquaculture systems.

Calcareous sand is widely observed in the foundation of off-shore infrastructure. Although a lot of research has been carried out on the mechanical properties of calcareous sand, study into the influence of the stress–strain path on the mechanical behaviour of calcareous sand is very limited. In this study, a series of triaxial tests were performed on calcareous sand under three different stress paths. The particle morphology of calcareous sand before and after the tests, the stress–strain relationship under different stress paths, and the characteristics of shear strength and deformation were investigated. The results show that the consolidation pressure and stress path have significant effects on the volume strain, strength, and particle breakage of calcareous sand. In addition, the underlying mechanisms of the different behaviours of calcareous sand observed in this study were discussed.

A hyperspectral image (HSI) is often corrupted by various types of noise during image acquisition, e.g., Gaussian noise, impulse noise, stripes, deadlines, and more. Thus, as a preprocessing step, HSI denoising plays a vital role in many subsequent tasks. Recently, a variety of mixed noise removal approaches have been developed for HSI, and the methods based on spatial–spectral double factor and total variation (DFTV) regularization have achieved comparable performance. Additionally, the nonlocal low-rank tensor model (NLR) is often employed to characterize spatial nonlocal self-similarity (NSS). Generally, fully exploring prior knowledge can improve the denoising performance, but it significantly increases the computational cost when the NSS prior is employed. To solve this problem, this article proposes a novel DFTV-based NLR regularization (DFTVNLR) model for HSI mixed noise removal. The proposed model employs low-rank tensor factorization (LRTF) to characterize the spectral global low-rankness (LR), introduces 2-D and 1-D TV constraints on double-factor to characterize the spatial and spectral local smoothness (LS), respectively. Meanwhile, the NLR is applied to the spatial factor to characterize the NSS. Then, we developed an algorithm based on proximal alternating minimization (PAM) to solve the proposed model effectively. Particularly, we effectively controlled the computational cost from two aspects, namely taking small-sized double factor as regularization object and putting the time-consuming NLR model before the main loop with fewer iterations to solve it independently. Finally, considerable experiments on simulated and real noisy HSI substantiate that the proposed method is superior to the related state-of-the-art methods in balancing the denoising effect and speed.

Karst rivers are highly susceptible to environmental disturbance due to their robust hydraulic connectivity. However, current knowledge of the mechanisms that regulate the assembly of bacterial and protistan subcommunities in river ecosystems, particularly in karst regions, is limited. By employing 16S and 18S rRNA gene amplicon sequencing, we explored how the diversities and assembly of abundant and rare bacterial and protistan subcommunities adapt to the local environmental variables in a karst river. Both bacterial and protistan rare subcommunities in karst river environments showed a similar biogeography to their abundant subcommunities. Also, a significant distance-decay pattern was observed in all components of the bacterial and protistan subcommunities along the Chishui River, with the rare subcommunities showing a more pronounced distance-decay pattern compared to the abundant subcommunities. Except protist rare subcommunity, the abundant and rare bacterial and abundant protistan subcommunities were strongly structured by the dispersal limitation processes rather than heterogeneous selection. Either bacteria or temperature, elevation and conductivity were the primary drivers for both abundant and rare subcommunities. Additionally, our results suggested that the rare subcommunities contribute significantly to the persistence and stability of microbial networks in the Chishui River, as they exhibited a higher number of keystones compared to the abundant subcommunities. Overall, our study revealed that in the karst river ecosystem, abundant bacterial subcommunities had a higher potential for environmental adaptation than rare bacterial and protistan subcommunities and identified the factors that moderate their assembly processes.

Many bird species in montane regions exhibit altitudinal migration behavior; however, altitudinal migration of birds is still understudied, especially in Asia. Mt. Gongga (7556 ​m) is the highest peak of the Hengduan Mountains in Southwest China. The steep elevation gradient and the high bird diversity make the eastern slope of Mt. Gongga (Hailuo Valley) an ideal place for studying the altitudinal migration behavior patterns of birds. We synchronously recorded the local bird diversity, temperature and humidity at two sites (1800 and 3000 ​m a.s.l.) during three migration seasons from September 2020 to June 2021 to identify birds exhibiting altitudinal migration behavior. During our surveys, we recorded 146 bird species in total and 20 passerine bird species were altitudinal migrants according to our altitudinal migration formula. Among those 20 altitudinal migrant species, eight bird species displayed a typical altitudinal migration pattern (upward migration during the breeding season and downward migration during the non-breeding season). Moreover, temperature was correlated with the daily number of individuals (DNI) at each study site. Therefore, increasing temperatures possibly caused upward migration of birds (DNI decreased at 1800 ​m and increased at 3000 ​m) and vice versa. To further elaborate, the Rufous-gorgeted Flycatcher (Ficedula strophiata), the species with the most prominent altitudinal migration behavior, initiated upward migration at a temperature of 11–12 ​°C at 1800 ​m and initiated downward migration at a temperature of 12–13 ​°C at 3000 ​m. Besides, humidity was positively correlated with the DNI. Therefore, increasing humidity (equals to increasing rainfall or snow) possibly caused downward migration of birds (DNI increased) and vice versa. Furthermore, bird species exhibiting a typical altitudinal migration behavior pattern are feeding on insects. Thus, the spatial and temporal changes of the invertebrate biomass might be an important ecological driver for the altitudinal migration of invertivorous (birds eating invertebrates) birds. This study provides fundamental data for the altitudinal migration of birds in the Hengduan Mountains and shows how altitudinal migration is seasonally dynamic across an elevational gradient in a subtropical mountain region.

Abstract Background Nitrogen-fixing prokaryotes (diazotrophs) contribute substantially to nitrogen input in mangrove sediments, and their structure and nitrogen fixation rate (NFR) are significantly controlled by environmental conditions. Despite the well-known studies on diazotrophs in surficial sediments, the diversity, structure, and ecological functions of diazotrophic communities along environmental gradients of mangrove sediment across different depths are largely unknown. Here, we investigated how biological nitrogen fixation varied with the depth of mangrove sediments from the perspectives of both NFR and diazotrophic communities. Results Through acetylene reduction assay, nifH gene amplicon and metagenomic sequencing, we found that the NFR increased but the diversity of diazotrophic communities decreased with the depth of mangrove sediments. The structure of diazotrophic communities at different depths was largely driven by salinity and exhibited a clear divergence at the partitioning depth of 50 cm. Among diazotrophic genera correlated with NFR, Agrobacterium and Azotobacter were specifically enriched at 50–100 cm sediments, while Anaeromyxobacter, Rubrivivax, Methylocystis, Dickeya, and Methylomonas were more abundant at 0–50 cm. Consistent with the higher NFR, metagenomic analysis demonstrated the elevated abundance of nitrogen fixation genes (nifH/D/K) in deep sediments, where nitrification genes (amoA/B/C) and denitrification genes (nirK and norB) became less abundant. Three metagenome-assembled genomes (MAGs) of diazotrophs from deep mangrove sediments indicated their facultatively anaerobic and mixotrophic lifestyles as they contained genes for low-oxygen-dependent metabolism, hydrogenotrophic respiration, carbon fixation, and pyruvate fermentation. Conclusions This study demonstrates the depth-dependent variability of biological nitrogen fixation in terms of NFR and diazotrophic communities, which to a certain extent relieves the degree of nitrogen limitation in deep mangrove sediments. Video Abstract

ObjectiveProlonged mechanical ventilation in children undergoing cardiac surgery is related to the decrease in cardiac output. The pressure recording analytical method (PRAM) is a minimally invasive system for continuous hemodynamic monitoring. To evaluate the postoperative prognosis, our study explored the predictive value of hemodynamic management for the duration of mechanical ventilation (DMV).MethodsThis retrospective study included 60 infants who underwent cardiac surgery. Cardiac index (CI), the maximal slope of systolic upstroke (dp/dtmax), and cardiac cycle efficiency (CCE) derived from PRAM were documented in each patient 0, 4, 8, and 12 h (T0, T1, T2, T3, and T4, respectively) after their admission to the intensive care unit (ICU). A linear mixed model was used to deal with the hemodynamic data. Correlation analysis, receiver operating characteristic (ROC), and a XGBoost machine learning model were used to find the key factors for prediction.ResultsLinear mixed model revealed time and group effect in CI and dp/dtmax. Prolonged DMV also have negative correlations with age, weight, CI at and dp/dtmax at T2. dp/dtmax outweighing CI was the strongest predictor (AUC of ROC: 0.978 vs. 0.811, p < 0.01). The machine learning model suggested that dp/dtmax at T2 ≤ 1.049 or < 1.049 in combination with CI at T0 ≤ 2.0 or >2.0 can predict whether prolonged DMV (AUC of ROC = 0.856).ConclusionCardiac dysfunction is associated with a prolonged DMV with hemodynamic evidence. CI measured by PRAM immediately after ICU admission and dp/dtmax 8h later are two key factors in predicting prolonged DMV.

Karst rivers are particularly vulnerable to bacterial pollution because immigrations are easily diffused from the surrounding environments due to their strong hydraulic connectivity. However, the assembly mechanism in shaping riverine bacterial biogeography is still poorly understood, especially for an ecosystem in the karst area. Here, 16S rRNA genes were used to explore the spatiotemporal and biogeographical patterns of bacterial communities from the Chishui River in the dry and wet seasons, and explore the impact of external immigration on the assembly of water bacterial communities. Our results showed clear spatiotemporal patterns of bacterial communities with a more pronounced seasonal rather than spatial fluctuation, which appeared to be dependent on seasonal-related environmental factors (e.g., temperature and turbidity). The bacterial communities exhibited a significant (p < 0.05) distance–decay pattern in both seasons, and they had a stronger distance–decay relationship in the dry season than in the wet season. However, most of the biomarkers of different external immigrations did not show significant (p > 0.05) distance–decay patterns along the Chishui river, implying that the biomarkers could be used as indicators of external immigration (e.g., OTU_125 and OTU_536). Also, the tributaries were the main external immigration (20.44–83.68%) for the Chishui River, while other terrestrial immigration (e.g., livestock, the soil of the cropland, brewing wastewater treatment plant, and sewages) showed relatively little influence, which could be due to the hydrodynamic conditions (e.g., fragile rock–soil system and hydrological structure) of the karst river. Additionally, the assembly of water bacterial communities in the Chishui river was governed by more determinism (50.7–85.7%) than stochasticity (14.3–49.3%) in both the dry and wet seasons. We demonstrated that the bacterial community’s substantial variations are largely shaped by deterministic processes, thereby providing a better understanding of spatiotemporal patterns and mechanisms of the bacterial community in karst river waters.

Abstract Clarifying mechanisms underlying the ecological succession of gut microbiota is a central theme of gut ecology. Under experimental manipulations of zebrafish hatching and rearing environments, we test our core hypothesis that the host development will overwhelm environmental dispersal in governing fish gut microbial community succession due to host genetics, immunology, and gut nutrient niches. We find that zebrafish developmental stage substantially explains the gut microbial community succession, whereas the environmental effects do not significantly affect the gut microbiota succession from larvae to adult fish. The gut microbiotas of zebrafish are clearly separated according to fish developmental stages, and the degree of homogeneous selection governing gut microbiota succession is increasing with host development. This study advances our mechanistic understanding of the gut microbiota assembly and succession by integrating the host and environmental effects, which also provides new insights into the gut ecology of other aquatic animals.

As one of the most important ecosystems, grassland ecosystems maintain an abundance of flora and fauna, and provide humans with rich resources. The structure and function of most grassland ecosystems around the world have been significantly affected by human activity. The overgrazing of livestock and their feces has caused grassland degradation and flora and fauna losses. However, we know little about the relationship between grassland degradation, livestock feces and the arthropod community. In this study, we conducted surveys of the epigeic arthropod community in alpine grassland of the Zoige wetlands in eastern Qinghai-Tibetan Plateau, China. We used ANOVA, multiple linear regression and model-averaging to explore how grassland degradation and livestock feces affected epigeic arthropods community. We found that together grassland degradation and season differently affected taxonomic richness, abundance and different feeding groups of the epigeic arthropod community. Because of the influence of temperature on the epigeic arthropod, the taxonomic richness and abundance of epigeic arthropod community fluctuated dramatically among seasons. Epigeic arthropod community diversity had a significant positive correlation with plant height of all species and Compositae percentage cover in most levels of degradation. The amount of sheep feces had a significant negative correlation with taxonomic richness and abundance of the epigeic arthropod community, because overgrazing sheep reduces the availability of resources and the suitability of micro-habitats for epigeic arthropods. Our study found that moderate levels of disturbance can increase the richness and abundance of epigeic arthropod community over a short period of time.

Summary Microbial sulfate reduction and sulfur oxidation are vital processes to enhance organic matter degradation in sediments. However, the diversity and composition of sulfate‐reducing bacteria (SRB) and sulfur‐oxidizing bacteria (SOB) and their environmental driving factors are still poorly understood in aquaculture ponds, which received mounting of organic matter. In this study, bacterial communities, SRB and SOB from sediments of aquaculture ponds with different sizes of grass carp (Ctenopharyngodon idellus) were analysed using high‐throughput sequencing and quantitative real‐time PCR (qPCR). The results indicated that microbial communities in aquaculture pond sediments of large juvenile fish showed the highest richness and abundance of SRB and SOB, potentially further enhancing microbial sulfur cycling. Specifically, SRB were dominated by Desulfobulbus and Desulfovibrio, whereas SOB were dominated by Dechloromonas and Leptothrix. Although large juvenile fish ponds had relatively lower concentrations of sulfur compounds (i.e. total sulfur, acid‐volatile sulfide and elemental sulfur) than those of larval fish ponds, more abundant SRB and SOB were found in the large juvenile fish ponds. Further redundancy analysis (RDA) and linear regression indicated that sulfur compounds and sediment suspension are the major environmental factors shaping the abundance and community structure of SRB and SOB in aquaculture pond sediments. Findings of this study expand our current understanding of microbial driving sulfur cycling in aquaculture ecosystems and also provide novel insights for ecological and green aquaculture managements.

Gut microbiota and host interactions co-evolve and develop into stably adapted microbial communities and play vital roles in maintaining the health of organisms. Diet is supposed to be an important driver of differences in gut microbiota, but previous studies would commonly use literature depictions, which are essential but inaccurate, to explain the effects of diet on the gut microbiota of wild birds. In this study, we collected intestinal samples from five sympatric flycatchers to compare the gut microbial differences using bacterial 16S rRNA genes from Illumina MiSeq platform. Over 1,642,482 quality-filtered sequences from 18 16S rRNA libraries were obtained and distinct compositions and diversities of gut microbiota were found in five flycatchers. Their gut microbiota is mainly from the four bacterial phyla of Proteobacteria, Firmicutes, Actinomycetes, and Bacteroidetes, but at the genus level showed a significant difference. Functional predictions revealed that the metabolic capacity of the gut microbiota of five flycatchers is greatly distinguished at KEGG level 3. And multiple food fragments showed a significant correlation with gut microbiota. Besides, the significant differences in the specific composition of the diets of the five insectivorous flycatchers indicated the differentiation of dietary niches. The study of the gut microbiota and feeding habits of sympatric flycatchers would increase the understanding of the gut microbial diversity of wild birds, and also improve our cognition of the co-evolution and co-adaptation within the host gut microbiota relations.

Altitudinal bird migration involves seasonal shifts up and down the altitude gradient annually. Asia as the place with the largest number of altitudinal migrants, has quite few related studies, especially for montane and temperate avifaunas. To explore the potential drivers of seasonal altitudinal migration for birds in the middle of Hengduan Mountains, we conducted a three-year investigation on breeding and non-breeding season bird communities at eight elevational bands (1200–4200 ​m) in the Gongga Mountains. We examined the altitudinal migration patterns and relationships between seasonal distribution shifts and species' traits of 50 species with sufficient data recorded in both seasons. We found that a large proportion of breeding birds underwent altitudinal migration and showed three migration patterns (downslope shift, upslope shift, no shift). Seasonal distribution shifts were mainly correlated with certain ecological traits. Species breeding at high and mid-elevations, nesting in scrub and being omnivorous are more likely to show downslope movements during the non-breeding season. In addition, territorially weaker species exhibited more diverse migration patterns. Notably, we found the hand-wing index (HWI) was actually more convincing than body mass in explaining altitudinal migration. These results consolidate the studies of seasonal altitudinal migration in montane birds. Our study could be used to bridge existing knowledge gaps that currently impeding effective conservation for montane avifaunas in the Hengduan Mountains.

Microsatellites (SSRs) are widely distributed in the genomes of organisms and are an important genetic basis for genome evolution and phenotypic adaptation. Although the distribution patterns of microsatellites have been investigated in many phylogenetic lineages, they remain unclear within the morphologically and physiologically diverse avian clades. Here, based on high-quality chromosome-level genomes, we examined the microsatellite distribution patterns for 53 birds from 16 orders. The results demonstrated that each type of SSR had the same ratio between taxa. For example, the frequency of imperfect SSRs (I-SSRs) was 69.90–84.61%, while perfect SSRs (P-SSRs) were 14.86–28.13% and compound SSRs (C-SSRs) were 0.39–2.24%. Mononucleotide SSRs were dominant for perfect SSRs (32.66–76.48%) in most bird species (98.11%), and A(n) was the most abundant repeat motifs of P-SSRs in all birds (5.42–68.22%). Our study further confirmed that the abundance and diversity of microsatellites were less effected by evolutionary history but its length. The number of P-SSRs decreased with increasing repeat times, and longer P-SSRs motifs had a higher variability coefficient of the repeat copy number and lower diversity, indicating that longer motifs tended to have more stable preferences in avian genomes. We also found that P-SSRs were mainly distributed at the gene ends, and the functional annotation for these genes demonstrated that they were related to signal transduction and cellular process. In conclusion, our research provided avian SSR distribution patterns, which will help to explore the genetic basis for phenotypic diversity in birds.

Sperm whales are a marine mammal famous for the aromatic substance, the ambergris, produced from its colon. Little is known about the biological processes of ambergris production, and this study aims to investigate the genetic mechanism of ambergris production in the sperm whale based on its chromosome-level genome. Comparative genomics analyses found 1207 expanded gene families and 321 positive selected genes (PSGs) in the sperm whale, and functional enrichment analyses suggested revelatory pathways and terms related to the metabolism of steroids, terpenoids, and aldosterone, as well as microbiota interaction and immune network in the intestine. Furthermore, two sperm-whale-specific missense mutations (Tyr393His and Leu567Val) were detected in the PSG LIPE, which has been reported to play vital roles in lipid and cholesterol metabolism. In total, 46 CYP genes and 22 HSD genes were annotated, and then mapped to sperm whale chromosomes. Furthermore, phylogenetic analysis of CYP genes in six mammals found that CYP2E1, CYP51A and CYP8 subfamilies exhibited relative expansion in the sperm whale. Our results could help understand the genetic mechanism of ambergris production, and further reveal the convergent evolution pattern among animals that produce similar odorants.

ABSTRACT Understanding mechanisms governing the resistance and resilience of microbial communities is essential for predicting their ecological responses to environmental disturbances. Although we have a good understanding of such issues for soil and lake ecosystems, how ecological resistance and resilience regulate the microbiota in the fish gut ecosystem remains unclear. Using the zebrafish model, we clarified the potential mechanisms governing the gut microbiota after exposure to silver nanoparticles (AgNPs). Here, we explored the ecological resistance and resilience of gut microbiota in zebrafish exposed to different concentrations of AgNPs (i.e., 10, 33 and 100 μg/liter) for 15, 45, 75 days. The high-throughput sequencing analysis of the 16S rRNA gene showed that AgNP exposure significantly reduced the α-diversity of gut microbiota and resulted in obvious dynamics of community composition and structure. However, the rebound of zebrafish gut microbiota was pushed toward an alternative state after 15 days of AgNP exposure. We found that homogeneous selection was a more prevalent contributor in driving gut community recovery after AgNP exposure. The resilience and resistance of gut microbiota responses to AgNP disturbance might be mainly determined by the predominant keystone taxa such as Acinetobacter and Gemmata. This study not only expanded our understanding of fish gut microbiota’s responses to pollutants but also provided new insights into maintaining host-microbiome stability during environmental perturbations. IMPORTANCE Understanding the ecological mechanisms governing the resistance and resilience of microbial communities is a key issue to predict their responses to environmental disturbances. Using the zebrafish model, we wanted to clarify the potential mechanisms governing the resistance and resilience of gut microbiota after exposure to silver nanoparticles (AgNPs). We found that AgNP contamination significantly reduced the α-diversity of gut microbiota and resulted in obvious changes in community composition. The resilience and resistance of gut microbiota to AgNPs might be associated with the predominant keystone taxa (e.g., Acinetobacter and Gemmata). This study greatly expanded our understanding of how fish gut microbiota responds to environmental perturbations and maintains stability.

The modulation transfer function (MTF) is commonly used as an imaging quality criterion reflecting the spatial resolution capability of imaging systems. The modified edge methods based on ISO Standard 12233 are widely used in MTF measurement for various imaging fields with high confidence. However, there are two problems in the existing edge methods which limit the application in remote sensing (RS) field with complicated image quality and usually uncontrollable edge angle: a near-horizontal or near-vertical “small tilt angle straight (STAS)” edge is required, and the MTF measurement results show low robustness and non-uniqueness. In this study, the influence of edge angle, oversampling rate (OSR), region of interest (ROI), edge contrast, and random noise on the edge method accuracy is quantitatively analyzed, and a practical multidirectional MTF measurement edge method is proposed based on the above analysis results. The modified edge method adaptively determines the optimal OSR according to edge angle and combines multiple measurement states, such as multi-ROI extraction and multi-phase binning, to improve the robustness, accuracy, and practicality of the edge method.

The habitats of snow leopards (Panthera uncia) are heavily utilized as pasturelands on the Tibetan Plateau. Livestock can benefit the snow leopard populations via providing extra prey resources. However, livestock can negatively impact upon the distribution of snow leopards by competing with their wild prey. Therefore, how grazing affects snow leopard space use is variable and its underlying mechanisms are unclear. We used 188 camera traps to systematically investigate the activities of snow leopards, their main wild prey, i.e., blue sheep (Pseudois nayaur), and livestock (i.e. yaks) across 650 km2 of Gongga Mountain. We found that: (1) snow leopards were detected only in areas with higher occurrences of blue sheep, and the presence of blue sheep was crucial in driving snow leopard space use. (2) The detection frequencies of snow leopards and blue sheep were lower at sites with yaks than without yaks. (3) Yaks limited snow leopard space use mainly by competing with its main prey, blue sheep. Our results highlight that the competition pressure of livestock on wild ungulates can limit the activities of snow leopards. Grazing management should be improved for conservation of snow leopards at Gongga Mountain.

Abstract Background Global climate change has had significant effects on animal distribution and population dynamics in mid-latitude alpine areas, but we know little about the basic ecology of high-altitude species due to the difficulties of conducting field research in the harsh climate and habitat present at high elevations. The Tibetan Snowcock (Tetraogallus tibetanus) is a little-known phasianid distributing in alpine areas at extremely high elevations in the mountains surrounding the Tibetan Plateau. Estimating the species occupancy rate and discussing the factors affecting its distribution based on infrared-triggered camera techniques would provide both a baseline to measure the influence of global warming and valuable information on its conservation and ecology. Methods We used infrared-triggered cameras to investigate the Tibetan Snowcock on the western slope of Mt. Gongga from June to November 2016. We used the R package “overlap” to visualize its activity pattern, and used an occupancy model to both examine its habitat use as well as to determine the most influential variables affecting its habitat use. Results Using 103 camera traps over 9213 camera-days, we recorded 428 instances of Tibetan Snowcock. The diel activity peaks of Tibetan Snowcock occurred during the periods of 8:00‒10:00 am and 18:00‒20:00 pm. The model estimate of occupancy for Tibetan Snowcock (0.830) was slightly higher than the naïve site occupancy based on camera detections (0.663), indicating a wider use of habitat than the camera traps recorded. Elevation, slope, settlement density, road density, and EVI (enhanced vegetation index) were the most influential variables for its habitat use. Conclusions The Tibetan Snowcock is confirmed to be diurnal. This species prefers an environment with a high elevation, gentle slope, and low EVI, apparently facing a trade-off between predator risk, foraging efficiency, and food availability. When human impact was low, there was a positive correlation between the habitat use of the Tibetan Snowcock and both its road and settlement densities. Infrared cameras and proper survey design are valuable for investigating extreme alpine phasianids.

Abstract Background In biological systems, biological diversity often displays a rapid turn-over across elevations. This defining feature has made mountains classic systems for studying the spatial variation in diversity. Because patterns of elevational diversity can vary among lineages and mountain systems it remains difficult to extrapolate findings from one montane region to another, or among lineages. In this study, we assessed patterns and drivers of avian diversity along an elevational gradient on the eastern slope of Mt. Gongga, the highest peak in the Hengduan Mountain Range in central China, and a mountain where comprehensive studies of avian diversity are still lacking. Methods We surveyed bird species in eight 400-m elevational bands from 1200 to 4400 m a.s.l. between 2012 and 2017. To test the relationship between bird species richness and environmental factors, we examined the relative importance of seven ecological variables on breeding season distribution patterns: land area (LA), mean daily temperature (MDT), seasonal temperature range (STR), the mid-domain effect (MDE), seasonal precipitation (SP), invertebrate biomass (IB) and enhanced vegetation index (EVI). Climate data were obtained from five local meteorological stations and three temperature/relative humidity smart sensors in 2016. Results A total of 219 bird species were recorded in the field, of which 204 were recorded during the breeding season (April–August). Species richness curves (calculated separately for total species, large-ranged species, and small-ranged species) were all hump-shaped. Large-ranged species contributed more to the total species richness pattern than small-ranged species. EVI and IB were positively correlated with total species richness and small-ranged species richness. LA and MDT were positively correlated with small-ranged species richness, while STR and SP were negatively correlated with small-ranged species richness. MDE was positively correlated with large-ranged species richness. When we considered the combination of candidate factors using multiple regression models and model-averaging, total species richness and large-ranged species richness were correlated with STR (negative) and MDE (positive), while small-ranged species richness was correlated with STR (negative) and IB (positive). Conclusions Although no single key factor or suite of factors could explain patterns of diversity, we found that MDE, IB and STR play important but varying roles in shaping the elevational richness patterns of different bird species categories. Model-averaging indicates that small-ranged species appear to be mostly influenced by IB, as opposed to large-ranged species, which exhibit patterns more consistent with the MDE model. Our data also indicate that the species richness varied between seasons, offering a promising direction for future work.

The Lesser Sand-Plover (Charadrius mongolus atrifrons) is a small shorebird in Charadriiformes. Here we assembled the complete mitochondrial genome of C. m. atrifrons (Aves: Charadriiformes) which is 16,919 bp in length and consisting of 13 protein-coding (PCGs), 2 ribosomal RNA, 22 transfer RNA and 1 control region. The overall A + T content of was 55.5%. The Maximum Likelihood (ML) tree based on the 12 concatenated mitochondrial protein-coding genes (except ND6 gene) placed C. m. atrifrons in a clade with C. alexandrines but separate from C. vociferus.

Farmland is one of the most important ecosystems in the world, providing foods and habitats for humans as well as many wild animals. However, biodiversity in farmlands has been substantially impacted by the intensification of agriculture and changes in landscape. Increasing either the area of natural and semi-natural habitat or the proportion of biodiversity-friendly crops could potentially mitigate the decline of biodiversity, but at the same time they would affect the agricultural economic output and were not widely applied. To date, some studies have focused on whether crops or cropland heterogeneity has a positive impact on biodiversity, but the results were inconsistent and it is difficult to summarize the relationship between farmland heterogeneity and farmland biodiversity in general. Meanwhile, few papers have studied the differences in bird diversity among small-scale agriculture in China. We conducted a year-long field survey on the Chengdu Plain to explore the relationships of landscape composition and the heterogeneity of cropland and non-cropland with bird diversity and community structure across different seasons. Using generalized linear models (GLM) and generalized least squares (GLS) for data analysis, our results showed that bird diversity is positively correlated with natural woodlands but negatively correlated with commercial forests. Both crop and non-crop landscape compositional heterogeneity affect bird diversity and community structure, especially during the non-breeding season, as many high-altitude birds come down to the farmland for foraging. Both bird diversity and community structure are influenced by cropland configurational heterogeneity, but seldomly influenced by non-cropland configurational heterogeneity. We propose to maintain the area of natural habitat and increase the area of mixed commercial forests by replacing monocultures. Diversified crop and non-crop types with a reasonable layout could conserve farmland biodiversity and maintain the stability of local ecosystems. More research on landscape heterogeneity in small-scale agriculture is needed to provide better understanding of the relationship between the agricultural landscape and bird diversity.

Fish-associated microbial communities play important roles in host growth, health and disease in the symbiont ecosystem; however, their diversity patterns and underlying mechanisms in different body habitats remain poorly understood. Siganus fuscescens is one of the most important consumers of macroalgae and an excellent natural marine source of nutritional lipids for humans, and widely distributes in shallow coastal areas. Here we systematically studied the microbial communities of 108 wild S. fuscescens in four body habitats (i.e., skin, gill, stomach, and hindgut) and surrounding water. We found that the β-diversity but not α-diversity of fish-associated microbial communities from each habitat significantly (p < 0.05) increased as body weight increased. Also, opportunistic pathogens and probiotics (e.g., Pseudomongs, Methylobacterium) appeared to be widely distributed in different body habitats, and many digestive bacteria (e.g., Clostridium) in the hindgut; the abundances of some core OTUs associated with digestive bacteria, “Anaerovorax” (OTU_6 and OTU_46724) and “Holdemania” (OTU_33295) in the hindgut increased as body weight increased. Additionally, the quantification of ecological processes indicated that heterogeneous selection was the major process (46–70%) governing the community assembly of fish microbiomes, whereas the undominated process (64%) was found to be more important for the water microbiome. The diversity pattern showed that β-diversity (75%) of the metacommunity overweight the α-diversity (25%), confirming that the niche separation of microbial communities in different habitats and host selection were important to shape the fish-associated microbial community structure. This study enhances our mechanistic understanding of fish-associated microbial communities in different habitats, and has important implications for analyzing host-associated metacommunities.

The complete mitochondrial genome of Mycerobas carnipes was sequenced in this study and the total length is 16,806 bp containing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and one control region. The phylogenetic analysis based on 13 PCGs of five grosbeaks and other Fringillidae birds demonstrated that Mycerobas, Coccothraustes, and Eophona had close phylogenetic relationships for clustering as three sister branches, and supported that Eophona originated earlier in phylogeny.

The Oriental Skylark (Alauda gulgula) is a small songbird in the Alaudidae. Here we assembled the complete mitochondrial genome of Alauda gulgula which is 17,055 bp in length and consisting of 13 protein-coding genes (PCGs), 2 ribosomal RNA, 22 transfer RNA, and 2 extensive heteroplasmic control regions. The overall A + T content of the mitogenome is 52.3%The maximum-likelihood (ML) tree based on the complete mitochondrial genome of A. gulgula revealed the close genetic relationship between A. gulgula and A. arvensis, but separate from A. cheleensis.

Abstract Background The discrepant concordance between biopsy and radical prostatectomy (RP) specimen are well reported. To validate the clinical usefulness of neutrophil-lymphocyte ratio (NLR) in discriminating real GS ≥ 7 PCa from biopsy-based GS ≤ 6 PCa in comparison with serum total prostate-specific antigen (tPSA) and value of their combination. Methods One hundred one patients who underwent physical examinations incidentally found elevated tPSA and subsequently received biopsy with a conclusion of GS ≤ 6 and RP with an interval of 4-6 weeks after biopsy were enrolled. NLR and tPSA were obtained within 15 days prior to biopsy. Logistic regression model was applied appropriately; McNemar tests and AUC model were performed to evaluate differences among tPSA, NLR and their combination and corresponding diagnostic power respectively. Results The pathological results from RP specimen comprised 61 patients with GS ≤ 6 and 100 patients with GS ≥ 7. Higher tPSA and NLR were significantly associated with patients with actual GS ≥ 7 (All P

To effectively protect a species, understanding its habitat needs and threats across its life-history stages is necessary. The Black-necked Crane (Grus nigricollis) is an endangered wetland bird species of the Qinghai–Tibetan Plateau, which is an important grazing area in China. To overcome the conflict between increasing grazing activities and the protection of wild cranes, we investigated the variation of habitat utilization within the home range of cranes at different stages (preincubation, incubation, postfledging, and fully fledged stages). We manually tracked 13 pairs of cranes in the Zoige international wetland, used the fixed-kernel-polygon (FKP) method to determine home-range size, and used satellite images to identify different habitat types. The average home-range size was 143.38 ± 34.46 ha. Cranes were most often located in meadow habitats followed by marsh meadows and marshes. During the postfledging stage, home-range size was significantly decreased, with the proportion of marsh habitat slightly increased. Since this stage is crucial for young-crane survival, research on the importance of marshes and effective protection measures should be further strengthened.

Mitochondrial genome sequences are valuable resources for systematics and conservation biology studies. In this paper, we present the complete mitogenome of Aquila nipalensis which was 18,450 bp in length. The gene content and arrangement were typical for avian mtDNA. The overall A + T content of was 54.1%, and the AT skew was calculated as 0.12 for the complete mitogenome of A. nipalensis. The maximum-likelihood (ML) tree based on the concatenated 12 protein-coding genes (PCGs) revealed the basal phylogenetic position of A. nipalensis in Aquila.

This study examines the relative importance of six variables: area, the mid-domain effect, temperature, precipitation, productivity, and habitat heterogeneity on elevational patterns of species richness for breeding birds along a central Himalaya gradient in the Gyirong Valley, the longest of five canyons in the Mount Qomolangma National Nature Reserve. We conducted field surveys in each of twelve elevational bands of 300 m between 1,800 and 5,400 m asl four times throughout the entire wet season. A total of 169 breeding bird species were recorded and most of the species (74%) were small-ranged. The species richness patterns of overall, large-ranged and small-ranged birds were all hump-shaped, but with peaks at different elevations. Large-ranged species and small-ranged species contributed equally to the overall richness pattern. Based on the bivariate and multiple regression analyses, area and precipitation were not crucial factors in determining the species richness along this gradient. The mid-domain effect played an important role in shaping the richness pattern of large-ranged species. Temperature was negatively correlated with overall and large-ranged species but positively correlated with small-ranged species. Productivity was a strong explanatory factor among all the bird groups, and habitat heterogeneity played an important role in shaping the elevational richness patterns of overall and small-ranged species. Our results highlight the need to conserve primary forest and intact habitat in this area. Furthermore, we need to increase conservation efforts in this montane biodiversity hotspot in light of increasing anthropogenic activities and land use pressure.

To elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE), we explore whether GSPE regulates the inflammatory response of TNBS-induced colitis in rats at the levels of NF-κB signal transduction pathway. Rats were intragastrically administered of different doses of GSPE (100, 200 and 400 mg·kg−1) per day for seven days after ulcerative colitis (UC) was induced by intracolonic injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Sulfasalazine (SASP) at 400 mg/kg was used as a positive control drug. The expression of nuclear factor-kappa B (NF-κB), phospho-I kappaB-alpha (pIκBα), inhibitor kappa B kinase (IκK) in the colon tissues were all measured by enzyme-linked immunosorbent assay (ELISA) methods. Treatment with GSPE reduced the expression of NF-κB, pIκBα and IκK in the colon. The results of this study show that GSPE exerts beneficial effects in inflammatory bowel disease by inhibition of NF-κB signal transduction pathways.

Copyright of Auk: Ornithological Advances is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The distribution of species and their causes are key questions for population ecology and conservation. Giant pandas (Ailuropoda melanoleuca) in the Daxiangling Mountains, China are part of an isolated population on the edge of the species' range and little is known regarding their distribution. Based on land cover, topography, human disturbance, and panda occurrence data in 2 national giant panda surveys, we used a species distribution model (i.e., MaxEnt) to simulate habitat distribution changes of the local panda population between 2001 and 2012. During this time the area of coniferous forest and broadleaf forest increased by 16.4% and 5.8%, respectively, whereas the shrub-grass and agricultural land decreased by 45.1% and 4.0%, respectively. Panda habitat increased from 460.3 km² in 2001 to 591.3 km² in 2012. Panda distribution in the Daxiangling Mountains was primarily influenced by land cover, topography, and human activities. Our study demonstrates that habitat recovery in the Daxiangling Mountains created a favorable environment for the local panda population; thus, the boundary of panda reserves should be adjustable based on their use of the landscape. Future research should focus on dispersal and distribution of pandas to better understand their land use for effective conservation. [ABSTRACT FROM AUTHOR]

Large-scale patterns of species richness have gained much attention in recent years; however, the factors that drive high species richness are still controversial in local regions, especially in highly diversified montane regions. The Qinghai-Tibetan Plateau (QTP) and the surrounding mountains are biodiversity hot spots due to a high number of endemic montane species. Here, we explored the factors underlying this high level of diversity by studying the relationship between species richness and environmental variables. The richness patterns of 758 resident bird species were summarized at the scale of 1°×1° grid cell at different taxonomic levels (order, family, genus, and species) and in different taxonomic groups (Passeriformes, Galliformes, Falconiformes, and Columbiformes). These richness patterns were subsequently analyzed against habitat heterogeneity (topographical heterogeneity and land cover), temperature amplitude (annual temperature, annual precipitation, precipitation seasonality, and temperature seasonality) and a vegetation index (net primary productivity). Our results showed that the highest richness was found in the southeastern part of the QTP, the eastern Himalayas. The lowest richness was observed in the central plateau of the QTP. Topographical heterogeneity and temperature amplitude are the primary factors that explain overall patterns of species richness in the QTP, although the specific effect of each environmental variable varies between the different taxonomic groups depending on their own evolutionary histories and ecological requirements. High species richness in the southeastern QTP is mostly due to highly diversified habitat types and temperature zones along elevation gradients, whereas the low species richness in the central plateau of the QTP may be due to environmental and energetic constraints, as the central plateau is harsh environment. [ABSTRACT FROM AUTHOR]

Background: Protein arginine methyltransferase 5 (PRMT5), a type II PRMT, is highly expressed in some tumors, but its role in hepatocellular carcinoma (HCC) is still unknown.Methods: PRMT5 level in HCC specimens was determined by immunohistochemical staining and the association with clinicopathologic features was evaluated. PRMT5 was inhibited by AMI-1 (a small molecule inhibitor of PRMTs) or small interference RNA (siRNA). The proliferation of HCC cells was tested by Cell Counting Kit-8, cell migration was evaluated by Transwell assay and cell cycle and apoptosis were analyzed by flow cytometry. The effect of AMI-1 on HCC in vivo was examined by mouse xenograft model.Results: PRMT5 expression was markedly upregulated in HCC tissues, and correlated inversely with overall patient survival. Knockdown of PRMT5 significantly reduced the proliferation of HCC cells, but did not affect the growth of normal liver cells. Furthermore, β-catenin was identified as a target of PRMT5. Silencing PRMT5 significantly down-regulated the expression of β-catenin and the downstream effector Cyclin D1 in HCC cells. AMI-1 strongly inhibited HCC growth in vivo, increased the ratio of Bax/Bcl-2, and led to apoptosis and loss of migratory activity in several HCC cells. Meanwhile, AMI-1 decreased the expression levels of symmetric dimethylation of H4 (H4R3me2s), a histone mark of PRMT5.Conclusions: PRMT5 plays an important role in HCC. PRMT5 may be a promising target for HCC therapy. [ABSTRACT FROM AUTHOR]

Landslides caused by the magnitude 8.0 Wenchuan Earthquakes had brought extensive habitat changes in the montane region. Until now, little is known about the non-volant small mammals in landslide disturbed areas. In this study, we compared the non-volant small mammal communities between seismic landslides and undisturbed areas in a broadleaved deciduous forest in the Longxi-Hongkou National Nature Reserve, Sichuan, China. Our goals were to understand the response of non-volant small mammal communities to landslide disturbance, and to explore the effect of vegetation recovery and source populations of non-volant small mammals on the recovery process of small mammal communities in landslides. Pitfall traps were set to capture non-volant small mammals in landslides and control sites from April 2010 to January 2014. Vegetation covers were visually estimated along with each small mammal trapping period. Our results showed that the relative abundance of non-volant small mammal communities in landslides were significantly lower than these in control sites. Shannon-Weiner diversity indices were higher in landslides. The relative abundance and species richness of non-volant small mammal communities in landslides were positively significantly correlated with non-volant small mammal communities in control sites, as well as the herb covers in landslides (P<0.05). We concluded that non-volant small mammals could recolonize in landslides soon after seismic landslides, but the communities were highly variable and still need more time to recover. The recovery of herb layer in landslides and source populations in undisturbed areas played important roles in promoting the recovery of non-volant small mammal communities in landslides. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Physiology & Pharmacology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE), we explore whether GSPE regulates the inflammatory response of TNBS-induced colitis in rats at the levels of NF-κB signal transduction pathway. Rats were intragastrically administered of different doses of GSPE (100, 200 and 400 mg·kg-1) per day for seven days after ulcerative colitis (UC) was induced by intracolonic injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Sulfasalazine (SASP) at 400 mg/kg was used as a positive control drug. The expression of nuclear factor-kappa B (NF-κB), phospho-I kappaB-alpha (pIκBα), inhibitor kappa B kinase (IκK) in the colon tissues were all measured by enzyme-linked immunosorbent assay (ELISA) methods. Treatment with GSPE reduced the expression of NF-κB, pIκBα and IκK in the colon. The results of this study show that GSPE exerts beneficial effects in inflammatory bowel disease by inhibition of NF-κB signal transduction pathways. [ABSTRACT FROM AUTHOR]

Shoot regeneration in most apple cultivars is sensitive to antibiotic selection, thus Agrobacterium-mediated transformation is of low efficiency. Our experiments confirmed that, with a moderate selection pressure (10 or 20 mg l-1 kanamycin), a high percentage of callus formation (67.0% or 54.8%, respectively) was observed. Over 80.0% or 95.6% of these calli were transgenic, although the efficiency of transgenic shoot regeneration was low. Modifying the kanamycin selection pressure, or shortening the time of kanamycin selection to 2 weeks, did not increase the efficiency of transformation. Multiplying suspension cultures could be produced from transgenic calli using single cells or small cell aggregates to initiate such cultures. When these transgenic cell aggregates were placed on regeneration medium without kanamycin selection, 17.3% of them regenerated shoots after 8 weeks, and at least 86 transgenic plants were obtained from one suspension culture line. This level of success makes it possible to obtain large numbers of transgenic apple plants from a single experiment for genetic breeding, and to study the mechanisms of integration of target genes. [ABSTRACT FROM AUTHOR]

A new type of capacitance-coupled contactless conductivity detection (C4D) system with sidewall electrodes was proposed for integration on a silicon-on-isolator–poly(dimethylsiloxane) (SOI-PDMS) hybrid low-voltage-driven electrophoresis microchip. By a microelectromechanical system process, the sidewall electrodes were fabricated precisely at either side of the separation channel. The area of the capacitor electrodes was the maximum value to improve the detection sensitivity with an enhanced capacitance effect. According to the simulation results, the structural parameters of the sidewall electrodes were determined as 550-μm length, 15-μm width, 80-μm separation distance, and 1-μm isolator thickness. The integrated microdevice with the SOI-PDMS hybrid electrophoresis microchip was very compact and the size was only 15 cm × 15 cm × 10 cm (width × length × height), which permitted miniaturization and portability. The detector performance was evaluated by K+ testing. The detection limit of the conductivity detector was determined to be 10-9 and 10-6 M for K+ in the static and electric-driven modes, respectively. Finally, the C4D was applied to low-voltage-driven electrophoresis on a microchip to carry out real-time measurement of the separation of amino acids. The separations of 10-4 M lysine and phenylalanine in the low-voltage-driven electrophoresis mode were performed with an electric field of 300 V/cm and were completed in less than 15 min with a resolution of 1.3. The separation efficiency was found to be 1.3 × 103 and 2.8 × 103 plates for lysine and phenylalanine, respectively, with a migration time reproducibility of 2.7 and 3.2%. The conductivity detection limit of amino acids achieved was 10-6 M. The proposed method for the construction of a novel C4D integrated on an SOI-PDMS hybrid low-voltage-driven electrophoresis microchip showed the most extensive integration and miniaturization of a microdevice, which is a further crucial step toward the realization of the “lab-on-a-chip” concept. [ABSTRACT FROM AUTHOR]

Interferon-α2a (IFN-α2a) has been used for the treatment of various viral infections and cancers for many years. However some untolerable side effects have limited its application in some aspects. To evaluate whether or not an oligopeptide containing GFE motif can home human IFN-α2a to specifictissues, a fusion gene was constructed by fusing the coding sequence of GFEpeptide (CGFECVRQCPERC), which was screened from phage display peptidelibrary, to the 3\' end of human IFN-αa gene by recombinant DNAtechnique. Fusion protein rhIFN-α2a-GFE was expressed in Escherichia coli as inclusion bodies using a T7 RNA polymerase expression system, pET-22b,refolded through dialysis and purified to homogeneity to >95% of purity byaffinity chromatography. Characterization by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and immunoblotting demonstratedthe authenticity of the fusion protein. Purified rhIFN-α2a-GFE was found to be functionally active in terms of its antiviral activity for about 2.5 × 108 IU/mg in vitro. Yields of the purified fusion protein were about 200 mg/L of culture medium. Tissue distribution assay in mouse showed that at 30 min IFN-α2a could be enriched sevenfold higher in lung in the targeted IFN group of mice than in the standard IFN group of mice, and last for a long time. At 1 h, IFN-αa in the targeted IFN group was still 4.02-fold higher than that in the standard group. This confirmed that GFE peptide has the ability to selectively deliver its fusion partner IFN-α2a to lungs. The results also showed that the IFN-α2a-GFE could be specifically enriched in kidney and liver. Its distribution in kidney was concordant with the finding of GFE receptor, MDP, in kidney. However, the IFN-α2a-GFE in liver may imply some significance in pharmacology and toxicology. [ABSTRACT FROM AUTHOR]