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Salinity stress triggers changes in plant morphology, physiology and molecular responses which can subsequently influence plant-insect interactions; however, these consequences remain poorly understood. We analyzed plant biomass, insect population growth rates, feeding behaviors and plant gene expression to characterize the mechanisms of the underlying interactions between the rice plant and brown planthopper (BPH) under salinity stress. Plant bioassays showed that plant growth and vigor losses were higher in control and low salinity conditions compared to high salinity stressed TN1 (salt-planthopper susceptible cultivar) in response to BPH feeding. In contrast, the losses were higher in the high salinity treated TPX (salt-planthopper resistant cultivar). BPH population growth was reduced on TN1, but increased on TPX under high salinity condition compared to the control. This cultivar-specific effect was reflected in BPH feeding behaviors on the corresponding plants. Quantification of abscisic acid (ABA) and salicylic acid (SA) signaling transcripts indicated that salinity-induced down-regulation of ABA signaling increased SA-dependent defense in TN1. While, up-regulation of ABA related genes in salinity stressed TPX resulted in the decrease in SA-signaling genes. Thus, ABA and SA antagonism might be a key element in the interaction between BPH and salinity stress. Taken together, we concluded that plant-planthopper interactions are markedly shaped by salinity and might be cultivar specific.

Head and neck squamous cell carcinomas (HNSCCs) harbor a subset of cells that are CD44(+) and present with malignancy and radiotherapy resistance. As a key regulator of self-renewal, Nanog expression not only determines cell fate in pluripotent cells but also mediates tumorigenesis in cancer cells; thus, we examined the role of Nanog in CD44(+) HNSCC. Three HNSCC cell lines, tumor xenografts, and patient tumors were examined. Nanog levels were significantly higher in CD44(+) HNSCC spheroids than in CD44(-) spheroids, and further increased when grown as spheroids to enrich for CSCs. CD44(+) spheroids showed a 3.4-7.5-fold increase in migration and invasion compared with CD44(-) spheroids and were resistant to radiation therapy, which was reversed by inhibiting Nanog. Nanog knockdown also decreased spheroid formation by 66.5-68.8%. Moreover, a phosphokinase array identified upregulated ERK1/2 signaling in CD44(+) HNSCC cells compared with that in CD44(-) cells. ERK1/2 signaling was found to regulate Nanog expression, aiding tumor progression, metastasis, and radiotherapy resistance. In xenograft models, the combination of radiation and Nanog or ERK1/2 inhibition inhibited tumor growth by 75.6% and 79.1%, respectively. In lung metastasis models, CD44(+) cells injected into the tail vein of mice led to significantly more lung metastases and higher Nanog expression level compared with that by ERK1/2-knockdown CD44(+) cells. Finally, in tumor tissues, CD44 and Nanog expression levels were correlated with tumorigenesis in HNSCC patients. Thus, targeting Nanog and the ERK1/2 signaling pathway may prevent or reverse CSC phenotypes and epithelial-mesenchymal transition that drive tumor progression, metastasis, and radiotherapy resistance in HNSCC.

Nigeria is an Afrotropical region with considerable ecological heterogeneity and levels of biotic endemism. Among its vertebrate fauna, reptiles have broad distributions, thus, they constitute a compelling system for assessing the impact of ecological variation and geographic isolation on species diversification. The red-headed rock agama, Agama agama , lives in a wide range of habitats and, thus, it may show genetic structuring and diversification. Herein, we tested the hypothesis that ecology affects its genetic structure and population divergence . Bayesian inference phylogenetic analysis of a mitochondrial DNA (mtDNA) gene recovered four well-supported matrilines with strong evidence of genetic structuring consistent with eco-geographic regions. Genetic differences among populations based on the mtDNA also correlated with geographic distance. The ecological niche model for the matrilines had a good fit and robust performance. Population divergence along the environmental axes was associated with climatic conditions, and temperature ranked highest among all environmental variables for forest specialists, while precipitation ranked highest for the forest/derived savanna, and savanna specialists. Our results cannot reject the hypothesis that niche conservatism promotes geographic isolation of the western populations of Nigerian A. agama . Thus, ecological gradients and geographic isolation impact the genetic structure and population divergence of the lizards . This species might be facing threats due to recent habitat fragmentation, especially in western Nigeria. Conservation actions appear necessary., (© The Author(s) (2019). Published by Oxford University Press on behalf of Editorial Office, Current Zoology.)

Salinization is one of the most critical abiotic stress factors for crops and a rising setback in agro-ecosystems. Changes in weather, land usage, and the salinization of irrigation water are increasing soil salinity of many farmlands. Increased soil salinity alters the plant quality, which subsequently may trigger bottom-up effects on herbivorous insect. We examined the bottom-up effect of salinity stress on population parameters of the brown planthopper (BPH), Nilaparvata lugens through rice (Oryza sativa L.) plant. The results revealed that salinity interfered with egg hatching of BPH. The nymphal development period, adult longevity, and oviposition were also influenced by salinity. Notable differences appeared in the intrinsic growth rate (r), the finite increase rate (λ) and the net reproduction rate (R0) of BPH, and a concentration-dependent effect was detected. Although salinity adversely affected BPH development, population projection predicted a successful growth of the BPH population in a relatively short time under the treatment of low and medium levels of salinity (6, 8, and 10 dS/m of NaCl), whereas higher salt concentrations (12 and 14 dS/m) lead to significant fitness costs in BPH populations. Our study predicts that BPH could become a problem in areas with lower and medium salinity and that those planthoppers may exacerbate the negative effects of salinity for rice production. This study will provide valuable information for understanding the field abundance and distribution of BPH on saline rice field, thus contributing to the development of eco-friendly strategies to manage this pest in saline ecosystems., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Herein, we describe the new agamid species Acanthosaura phongdienensis sp. nov. from central Vietnam based on morphological and genetic data. Males of the new medium-sized species have a snout-vent length of up to 77.4 mm and females up to 64.7 mm. In both genders, the tail is longer than the snout-vent length. A spine occurs on each side of the neck, the rostral scute is entire, and the nuchal and dorsal crests are continuous. A postorbital spine is about half as long as the diameter of the eye-ball, and small lateral scales intermix with large, keeled scales whose tips point backwards and upwards. The new species differs genetically from the closely related species A. brachypoda, A. coronata, and A. lepidogaster by uncorrected p-distances of 13.6%, 21.7%, and 12.8%, respectively. This is the 13th species of Acanthosaura and the eighth species in the genus from Vietnam.

Planthoppers (Nilaparvata lugens, Sogatella furcifera, and Laodelphax striatellus) (Hemiptera: Delphacidae) are the most important pests affecting rice production. Pesticide spraying for its control may cause harmful effects on human health and the environment, especially the loss of biodiversity. The consequences of these changes on biodiversity and ecological services are well studied in tropical irrigated paddy fields, but are largely unknown in subtropical areas. Organic regime provides an environment-friendly method for biodiversity conservation; however, it is unclear whether this regime can suppress planthopper populations effectively in paddy fields. Consequently, we compared species richness, abundance, community structure, and evenness of natural enemies and planthoppers between organic and conventional rice fields (n = 35) distributed across four sites in China. The results showed that species richness was higher in organic fields than in conventional fields. Shannon index and evenness of predators and parasitoids were higher in most of the organic fields than their conventional counterparts. Furthermore, planthopper density showed a significant negative relationship with increased richness and evenness for both predators and parasitoids. These results underscore the notion that management regimes influence biodiversity in rice field. Most importantly, this has direct implications on the efficacy of natural pest control services rendered by predators and parasitoids associated with planthoppers in China and potentially other rice production regions in Asia., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although sphingomyelins known to be are lipid constituents of the plasma membrane in vertebrates, much remains obscure about the metabolism of sphingomyelins in insects. With ultra performance liquid chromatography-time-of-flight-tandem mass spectrometry analysis, we revealed for the first time that sphingomyelins are abundant in Nilaparvata lugens (Stål), the brown planthopper (BPH), and their biosynthesis is carried out by sphingomyelin synthase-like protein 2 (SMSL2), which is homologous to sphingomyelin synthase-related protein (SMSr). Unlike other insect species, high concentrations of sphingomyelins rather than ceramide phosphoethanolamines exist in the BPH. Two putative genes, which are homologous to SMSr, are named Nilaparvata lugens SMS-like 1 (NlSMSL1) and 2 (NlSMSL2). Knockdowns of both NlSMSL2 and NlSMSL1 were conducted but only the first decreased concentrations of sphingomyelins in the BPH, indicating that NlSMSL2 plays a role in the biosynthesis of sphingomyelins. Real-time quantitative PCR analysis revealed both NlSMSL1 and NlSMSL2 are highly expressed in BPH adults, with NlSMSL1 specifically highly expressed in reproductive organs (ovaries and testes) whereas NlSMSL2 was highly expressed in the malpighian tubules. The knockdown of NlSMSL1 or NlSMSL2 increased BPH female body weight but not that of males, suggesting sex-specific roles for SMSLs in influencing BPH body weight. The results suggest that NlSMSL2 catalyses the synthesis of sphingomyelins and maintains female BPH body weight through alteration of sphingolipid content., (© 2018 The Royal Entomological Society.)

Viviparous (live-bearing) vertebrates have evolved repeatedly within otherwise oviparous (egg-laying) clades. Over two-thirds of these changes in vertebrate reproductive parity mode happened in squamate reptiles, where the transition has happened between 98 and 129 times. The transition from oviparity to viviparity requires numerous physiological, morphological, and immunological changes to the female reproductive tract, including eggshell reduction, delayed oviposition, placental development for supply of water and nutrition to the embryo by the mother, enhanced gas exchange, and suppression of maternal immune rejection of the embryo. We performed genomic and transcriptomic analyses of a closely related oviparous-viviparous pair of lizards ( Phrynocephalus przewalskii and Phrynocephalus vlangalii ) to examine these transitions. Expression patterns of maternal oviduct through reproductive development of the egg and embryo differ markedly between the two species. We found changes in expression patterns of appropriate genes that account for each of the major aspects of the oviparity to viviparity transition. In addition, we compared the gene sequences in transcriptomes of four oviparous-viviparous pairs of lizards in different genera ( Phrynocephalus , Eremias , Scincella , and Sphenomorphus ) to look for possible gene convergence at the sequence level. We discovered low levels of convergence in both amino acid replacement and evolutionary rate shift. This suggests that most of the changes that produce the oviparity-viviparity transition are changes in gene expression, so occasional reversals to oviparity from viviparity may not be as difficult to achieve as has been previously suggested., Competing Interests: Conflict of interest statement: D.D.P. and G.Z. are coauthors on a 2014 paper.

Background: miR-30a is a microRNA associated with the progression of malignant tumors such as gastric cancer, colon cancer, prostate cancer, and lung cancer, and can regulate the proliferation and migration of breast cancer (BC) cells in vitro. However, its expression, function, clinical significance and relationship with the Wnt/β-catenin pathway in human BC were still unclear., Methods: Immunohistochemistry, Western blotting and real-time quantitative PCR (RT-qPCR) were used to measure the expressions of miR-30a and β-catenin in 114 pairs of human BC tumor tissues and adjacent normal tissues which were collected from March 2014 to October 2015. The effect of miR-30a on the expression of β-catenin was studied in the MCF-7 cells in vitro., Results: The expression levels of miR-30a in human BC tumor tissues were significantly lower than they were in the adjacent normal tissues (P < 0.001), and significantly higher in β-catenin protein (P < 0.001), but there was no significant different in β-catenin mRNA (P = 0.3816). The immunohistochemistry results showed that β-catenin protein was only expressed on the cell membrane in paracancerous normal tissues, but β-catenin protein was expressed on the cell membrane and cytoplasm in BC tumor cells. In addition, there was a significantly negative correlation (r = -0.816, P < 0.001) between the expression miR-30a and β-catenin protein in BC tissues. The age of onset, PR expression, ER expression, and HER-2 expression of the BC patients were not related to miR-30a or β-catenin protein expression (P > 0.05). Tumor diameter, histological grade, lymph node metastasis, TNM stage, and the prognosis of BC patients (P < 0.05) were significantly related to miR-30a or β-catenin protein expression. In MCF-7 cells, miR-30a regulated the accumulation of β-catenin protein by inhibiting the expression of BCL9 in BC cells., Conclusion: miR-30a was lowly expressed in breast cancer tissues and highly in β-catenin protein, and miR-30a might block the Wnt/β-catenin pathway by inhibiting the accumulation of β-catenin, and then inhibiting breast cancer progression., Competing Interests: None., (IJCEP Copyright © 2019.)

Background: The insect gustatory system plays a central role in the regulation of multiple physiological behaviors and the co-evolution between insects and their hosts. The gustatory receptors (Gr) are important to allow insects to sense their environment. It is critical to the selection of foods, mates and oviposition sites of insects. In this study, the Gr family genes of the brown planthopper (BPH) Nilaparvata lugens Stål (Hemiptera: Delphacidae) were identified and analyzed, and their potential relationship to the fecundity of BPH was explored by RNA interference (RNAi)., Results: We identified 32 putative Gr genes by analyzing transcriptome and genome data from BPH. Most of these Gr proteins have the typical structure of seven transmembrane domains. The BPH Gr genes (NlGrs) were expressed in virtually all tissues and stages, whilst higher transcript accumulations were found in adult stages and in the midguts of females. Based on the phylogenic analysis, we classified NlGrs into five potential categories, including 2 sugar receptors, 2 Gr43a-like receptors, 7 CO 2 receptors, 5 bitter receptors and 13 NlGrs with unknown functions. Moreover, we found that 10 NlGrs have at least two alternative splicing variants, and obtained alternative splicing isoforms of 5 NlGrs. Finally, RNAi of 29 NlGrs showed that 27 of them are related to the transcript levels of two fecundity related genes vitellogenin and vitellogenin receptor., Conclusions: We found 32 Gr genes in BPH, among which at least 27 are required for normal expression of fecundity markers of this insect pest. These findings provide the basis for the functional study of Grs and the exploration of potential genes involved in the monophagous character of BPH.

Summary Otosclerosis is not often seen in the clinic, but it can seriously affect the quality of life due to the hearing loss of patients. Currently, the treatment of otosclerosis is mainly surgery. With the development of microsurgical techniques, the treatment of surgery for otosclerosis has been highly praised and widely carried out. However, different surgical methods, assistive techniques and instruments used during surgery, selected placement of prostheses, and varying levels of experience of the surgeon can all affect postoperative outcomes. In order to provide reference for the surgical treatment of otosclerosis in the future，this paper will summarize the factors related to postoperative efficacy of stapes surgery for otosclerosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Gastric cancer is a common malignancy worldwide. The prognosis of early stage gastric cancer patients has significantly improved in recent years. However, in progressive stage gastric cancer patients, the prognosis remains relatively poor due to tumor metastases. In our previous study, we showed that the expression of miR‑711 in gastric cancer tissues is low, and restoration of miR‑711 inhibited the invasion and migration and the occurrence of epithelial‑mesenchymal transition (EMT) in gastric cancer cells. Yet, the mechanisms involved in these processes remain unknown. In the present study, we demonstrated that miR‑711‑mediated downregulation of CD44 expression inhibited EMT of gastric cancer cells in vitro and in vivo by downregulating vimentin protein expression and upregulating E‑cadherin protein expression through transfection, qRT‑PCR and western blotting. Therefore, miR‑711 may provide a promising target for EMT‑related therapy for gastric cancer.

Most living organisms developed the innate clock system to anticipate daily environmental changes and to enhance their chances of survival. timeless (tim) is a canonical clock gene. It has been extensively studied in Drosophila melanogaster (Diptera: Drosophilidae) as a key component of the endogenous circadian clock, but its role is largely unknown in some agriculture pests. Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae), an important rice pest, exhibits a robust locomotor rhythm. In the present study, we cloned tim gene (ls-tim) from L. striatellus and investigated its function in the regulation of behavioral rhythms. Quantitative real-time polymerase chain reaction revealed a circadian expression pattern of ls-tim under different light conditions with a trough in the photophase and a peak in the late scotophase. After the knockdown of ls-tim via RNA interference (RNAi), the adults showed an earlier onset of locomotor activity under light/dark cycles and became arrhythmic in constant darkness. ls-tim RNAi also abolished the timing of adult emergence that normally occurs in the early photophase. These results suggest that ls-tim is essential for the light-entrained circadian rhythms in L. striatellus and provide more insights into the endogenous clock network underlying the behavioral and physiological rhythms of this insect.

The aim of the current study was to discuss and analyze computerized tomography (CT) features and clinicopathological characteristics of patients with Kimura disease in head and neck. CT and clinicopathological data of 12 patients with Kimura disease diagnosed between May 2011 and May 2015 were analyzed. The mean age was 43.9 years and the disease course varied from 1 week-20 years. The mean absolute value of eosinophil granulocytes was 1.95×10 9 /l. Multiple nodules were detected in 4 patients with Kimura disease. Main symptoms included multiple enlarged lymph nodes in neck and submaxillary regions. CT imaging of nodular lesions revealed a clear boundary, with moderate to marked homogeneous enhancement. Diffuse mass lesions were observed in 6 patients with Kimura disease. Main symptoms included subcutaneous diffuse soft tissue mass in parotid gland and maxillofacial regions. CT imaging of diffuse mass revealed unclear boundaries, adjacent skin thickness and moderate heterogeneous enhancement. In some cases, the diffuse mass involved soft mass with unclear boundaries. Pathological symptoms of Kimura disease included infiltration of eosinophilia, lymphocytic proliferation, formation of lymphatic follicles and variable degrees of fibrosis and vascular proliferation. Diagnosis of Kimura disease in head and neck regions may be improved based on lesions with clear or unclear boundaries, homogeneous or heterogeneous enhancement, with or without lymphadenectasis and by the presence of peripheral blood eosinophilia. However, a final diagnosis relies on a pathological examination.

Polygoni Multiflori Radix (PMR, Heshouwu in Chinese), derived from the tuberous roots of Polygonum multiflorum Thunb., is a widely-used Chinese medicinal material. For traditional clinical use, raw PMR (RPMR) is processed by nine cycles of steaming and drying to generate processed PMR (PPMR); RPMR and PPMR have distinct medicinal purposes based on the theory of traditional Chinese medicine. While PMR has been processed for hundreds of years, including the present, the chemistry of that processing has not been well studied. In this study, targeted and untargeted metabolomics analyses using ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) and ultra-performance liquid chromatography-quadrupole/triple quadrupole mass spectrometry (UPLC-QqQ-MS/MS) were integrated to investigate the processing chemistry of PMR. The results demonstrate that processing by nine cycles of steaming and drying qualitatively and quantitatively alters the chemical profile of PMR. Several mechanisms, namely hydrolysis, dehydration, isomerization, and Maillard reaction appear to be involved in the chemical transformation that occurs. The qualitative and quantitative data further suggest that nine cycles might be necessary for the preparation of PPMR, as PPMR that has been processed nine times shows significant differences in its chemical profile.

Cyrtorhinus lividipennis Reuter (Hemiptera: Miridae) is an important egg predator of planthoppers which are destructive rice pests. The chemosensory genes in the mirid antennae play important roles in mating and prey-seeking behaviors. To gain a better understanding of the olfaction of C. lividipennis, we sequenced the antennal transcriptomes of the predator to identify the key olfaction genes. We identified 18 odorant binding proteins (OBPs), 12 chemosensory proteins (CSPs), 1 Niemann-Pick C2 protein (NPC2), 15 odorant receptors (ORs), 6 ionotropic receptors (IRs), 3 gustatory receptors (GRs) and 3 sensory neuron membrane proteins (SNMPs). Quantitative real-time PCR results showed that the relative transcript levels of three ClivORs (ClivOR6, 7 and 14) in the female antennae were 3 to 6 folds higher than that in the male antennae, indicating these genes were more related to oviposition site selection. The relative transcript levels of ClivCSP8 and ClivOR11 were 2.6 and 2.7 times higher in the male antennae than that of the female, respectively, indicating that these genes might be involved in mate searching. Moreover, the responses of dsorco treated predators to volatiles emitted from infested rice were significantly reduced, indicating these volatiles might serve as crucial cues in the host searching of C. lividipennis.

The grain contamination by Aspergillus spp. has been a serious issue. This study exhibited the excellent antifungal effects of the essential oil compounds (EOCs) geraniol and citral against common grain pathogens ( A. flavus and A. ochraceus ) in vitro and in situ. The inhibitory mechanisms were also evaluated from the perspective of cell membrane permeability, reactive oxygen species (ROS) generation, and Aspergillus spp. growth-related gene expression. Meanwhile, the combined effects of EOCs in the vapor phase and modified atmosphere packaging (MAP) were examined to find an alternative preservation method for controlling Aspergillus spp. The results indicated that citral exhibited the antifungal activity mainly by downregulating the sporulation- and growth-related genes for both pathogens. Geraniol displayed inhibitory effectiveness against A. flavus predominantly by inducing the intracellular ROS accumulation and showed toxicity against A. ochraceus principally by changing cell membrane permeability. Furthermore, the synthetic effects of EOCs and MAP (75% CO₂ and 25% N₂) induced better grain quality than the current commercial fumigant AlP. These findings reveal that EOCs have potential to be a novel grain preservative for further application.

Southeast Asia and southern China (SEA-SC) harbor a highly diverse and endemic flora and fauna that is under increasing threat. An understanding of the biogeographical history and drivers of this diversity is lacking, especially in some of the most diverse and threatened groups. The Asian leaf-litter frog genus Leptolalax Dubois 1980 is a forest-dependent genus distributed throughout SEA-SC, making it an ideal study group to examine specific biogeographic hypotheses. In addition, the diversity of this genus remains poorly understood, and the phylogenetic relationships among species of Leptolalax and closely related Leptobrachella Smith 1928 remain unclear. Herein, we evaluate species-level diversity based on 48 of the 53 described species from throughout the distribution of Leptolalax. Molecular analyses reveal many undescribed species, mostly in southern China and Indochina. Our well-resolved phylogeny based on multiple nuclear DNA markers shows that Leptolalax is not monophyletic with respect to Leptobrachella and, thus, we assign the former to being a junior synonym of the latter. Similarly, analyses reject monophyly of the two subgenera of Leptolalax. The diversification pattern of the group is complex, involving a high degree of sympatry and prevalence of microendemic species. Northern Sundaland (Borneo) and eastern Indochina (Vietnam) appear to have played pivotal roles as geographical centers of diversification, and paleoclimatic changes and tectonic movements seem to have driven the major divergence of clades. Analyses fail to reject an "upstream" colonization hypothesis, and, thus, the genus appears to have originated in Sundaland and then colonized mainland Asia. Our results reveal that both vicariance and dispersal are responsible for current distribution patterns in the genus., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To evaluate the anticoagulation efficacy of dabigatran etexilate for left atrial appendage (LAA) thrombus resolution in patients with atrial fibrillation by transthoracic echocardiography and transesophageal echocardiography, and to investigate the anticoagulation factors.A total of 58 atrial fibrillation patients with LAA thrombus in our hospital were enrolled. After dabigatran etexilate anticoagulation for 3 months, the patients were divided into the effective group and ineffective group according to dissolution of thrombosis. The baseline data and the left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction, LAA flow velocity (LAA-v), and LAA thrombus size before and after anticoagulation treatment were recorded, and the measurement index were statistically analyzed.After the patients received anticoagulation treatment for 3 months, 15 patients had complete dissolution, thrombus in 21 patients reduced significantly, and the complete dissolution rate was 25.9% (15/58), the effective rate of dissolution was 62.1% (36/58). Compared with the ineffective group, the proportion of persistent atrial fibrillation and LAD in effective group were lower than those in the ineffective group, the LAEF and LAA-v in the effective group were higher than those in the ineffective group, and the differences were statistically significant (P < .05). Multivariate logistic regression analysis on the baseline data and each ultrasound index showed that the type of atrial fibrillation, LAD, LAEF, and LAA-v were independently associated with the efficacy of anticoagulation (P < .05).Dabigatran etexilate is effective in dissolution of LAA thrombus in patients with atrial fibrillation, and the atrial fibrillation type, LAD, LAEF, and LAA-v are significantly related with the efficacy of anticoagulation.

Tibetan frogs, Nanorana parkeri , are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89-95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including DNAJC8 in the brain, TNNC1 and ADORA1 in the heart, and LAMB3 in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Fifty-five soil samples were collected across the central and eastern Qinghai-Tibetan Plateau during July to August in 2013. These were analyzed for the sixteen polycyclic aromatic hydrocarbons (PAHs) called out by the USA EPA. The concentration characteristics, sources, and potential ecological risk assessment of the sixteen PAHs in the soils were investigated. The soils were extracted by ultrasonic extraction, purified by an HLB solid-phase extraction column, and quantified by gas chromatography-mass spectrometry (GC-MS). The total PAH concentrations ranged from 40.47 to 1276.40 μg·kg -1 , with a mean of 267.97 μg·kg -1 . Low-ring PAHs (two and three rings PAHs) were dominant in all samples, and the proportion of phenanthrene was the highest. The sources of PAHs were assessed by diagnostic ratios and a principal component analysis (PCA), which indicated that the main sources of the PAHs originated from petroleum and biomass combustion. The toxic equivalent concentration (TEQ) concentration of benzopyrene-(a)-pyrene (TEQ BaP ) in soils ranged from 3.73 to 79.32 μg·kg -1 , with an average concentration of 12.84 μg·kg -1 . The TEQ BaP in 4% of the soil samplings exceeded the Dutch target reference value (33.00 μg·kg -1 ), suggesting that a small portion of the soils in the Qinghai-Tibetan Plateau have potential ecological risk.

Most living organisms have developed internal circadian clocks to anticipate the daily environmental changes. The circadian clocks are composed of several transcriptional-translational feedback loops, in which cryptochromes (CRYs) serve as critical elements. In insects, some CRYs act as photopigments to control circadian photoentrainment, while the others act as transcriptional regulators. We cloned and characterized two cryptochrome genes, the Drosophila -like ( lscry1 ) and vertebrate-like ( lscry2 ) genes, in a rice pest Laodelphax striatellus . Quantitative real-time PCR showed that lscry1 and lscry2 expressed ubiquitously from nymph to adult stages as well as in different tissues. The transcript levels of lscry2 fluctuated in a circadian manner. Constant light led to arrhythmic locomotor activities in L. striatellus . It also inhibited the mRNA oscillation of lscry2 and promoted the transcription of lscry1 . Knockdown of lscry1 or lscry2 by RNA interference (RNAi) reduced the rhythmicity of L. striatellus in constant darkness, but not in light dark cycles. These results suggested that lscry1 and lscry2 were putative circadian clock genes of L. striatellus , involved in the regulation of locomotor rhythms.

Validamycin A (Val-A) is produced by Streptomyces as a secondary metabolite with wide agricultural applications of controlling rice sheath blight, false smut and damping-off diseases. The effect of alkaline pH shock on enhancing Val-A production and its mechanism were investigated. A higher yield of Val-A was achieved by NaOH shock once or several times together with faster protein synthesis and sugar consumption and alkaline pH shock can increase Val-A production by 27.43%. Transcription of genes related to amino acid metabolism, carbon metabolism and electron respiratory chain was significantly up-regulated, accompanied by the substantial increase of respiratory activity and glutamate concentration. Val-A production was promoted by a series of complex mechanisms and made a response to pH stress signal, which led to the enhancement of glutamate metabolism and respiration activity. The obtained information will facilitate future studies for antibiotic yield improvement and the deep revealment of molecular mechanism., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Class three semaphorins were originally identified as mediators of axon guidance, which repelled axons and collapsed growth cones. As a member of class three semaphorins, semaphorin3F (Sema3F) has been found to have similar effects on tumor cells and endothelial cells and also is implicated in the signaling of tumor metastasis by forming a complex with neuropilins and plexins. In this study, our laboratory produced a monoclonal antibody against the C-terminal domain of Sema3F (Sema3Fc mAb) using the hybridoma method, expecting to explore the potential role of the antibody and its application in the detection of Sema3F. The capture enzyme-linked immunosorbent assay (ELISA) method indicated that mAb belonged to the IgM subclass and purified Sema3Fc mAb had a titer of 5.12 × 10 5 against Sema3Fc by indirect ELISA. In addition, results showed that the Sema3Fc mAb could be applied in such experiments as Western blotting, flow cytometry, immunofluorescence, and immunocytochemical staining. It indicates the Sema3Fc mAb is available in the detection of Sema3F with specificity and will help further study the role and mechanism of Sema3F among tumor cells.

Ceramidases (CDases) are vital enzymes involved in the biosynthesis of sphingolipids, which are essential components of eukaryotic membranes. The function of these enzymes in insects, however, is poorly understood. We identified a neutral ceramidase (NlnCDase) from the brown planthopper, Nilaparvata lugens, one of the most destructive hemipteran pests of rice. The C12-ceramide was the most preferred substrate for the NlnCDase enzyme. The activity of the NlnCDase enzyme was highest in the neutral-pH range (pH 6.0). It was inhibited by EGTA, Cs + and Fe 2+ , while stimulated by EDTA and Ca 2+ . Moreover, the NlnCDase has higher transcript level and activity in adults than in eggs and nymphs, and in the reproductive organs (ovaries and spermaries) than in other tissues (i.e. heads, thorax, legs, midguts), which suggested that the NlnCDase might be elevated to mediate developmental process. In addition, transcripts and activity of the NlnCDase were up-regulated under abiotic stresses including starvation, abnormal temperature, and insecticides, and biotic stress of resistant rice varieties. Knocking down NlnCDase by RNA interference increased female survival under starvation and temperature stresses, suggesting that NlnCDase might be involved in the stress response in N. lugens.

Objective: Tumor was reported to correlate with inflammation and the host's inflammatory response to tumor has been shown to independently predict the outcome. Many measures of the systemic inflammatory response have been studied in recent years. In the present study the full blood count (leukocyte, neutrophil, lymphocyte) of colorectal cancers (CRCs) adenomatous polyps, and healthy people were collected, and the difference of ratios was studied., Patients and Methods: A total of 752 individuals (242 colorectal cancers, 248 adenomatous polyps, and 262 healthy people) were randomized enrolled in the present study. The full blood counts (leukocyte, neutrophil, and lymphocyte) of each individual were collected and the NLRs were calculated., Results: The leukocyte count, neutrophil ratio and neutrophil-lymphocyte ratio were the highest in colorectal cancer group, the second in adenomatous polyp group, and the lowest in healthy control (p < 0.001). The lymphocyte ratio was in the reverse order (p < 0.001). The ROC curve analysis showed that sensitivity and specificity levels of NLR were 66.9% and 77.6% for CRCs, 36.7% and 80.9% for adenomatous polyp. The leukocyte count was higher in the advanced adenomatous polyp compared with low-risk group (p = 0.042). Further analyses of the diagnostic value of NLR are warranted in the future., Conclusions: Difference of leukocyte count, neutrophil ratio and NLR may provide available information in the differential diagnosis of CRC, adenomatous polyp and healthy people.

Soil amended with single biochar or nitrogen (N) fertilizer has frequently been reported to alter soil nitrification process due to its impact on soil properties. However, little is known about the dynamic response of nitrification and ammonia-oxidizers to the combined application of biochar and N fertilizer in intensive vegetable soil. In this study, an incubation experiment was designed to evaluate the effects of biochar and N fertilizer application on soil nitrification, abundance and community shifts of ammonia-oxidizing bacteria (AOB) and ammonia oxidizing archaea (AOA) in Hangzhou greenhouse vegetable soil. Results showed that single application of biochar had no significant effect on soil net nitrification rates and ammonia-oxidizers. Conversely, the application of only N fertilizer and N fertilizer + biochar significantly increased net nitrification rate and the abundance of AOB rather than AOA, and only AOB abundance was significantly correlated with soil net nitrification rate. Moreover, the combined application of N fertilizer and biochar had greater effect on AOB communities than that of the only N fertilizers, and the relative abundance of 156 bp T-RF (Nitrosospira cluster 3c) decreased but 60 bp T-RF (Nitrosospira cluster 3a and cluster 0) increased to become a single predominant group. Phylogenetic analysis indicated that all the AOB sequences were grouped into Nitrosospira cluster, and most of AOA sequences were clustered within group 1.1b. We concluded that soil nitrification was stimulated by the combined application of N fertilizer and biochar via enhancing the abundance and shifting the community composition of AOB rather than AOA in intensive vegetable soil.

Rabies remains an important worldwide health problem. Newcastle disease virus (NDV) was developed as a vaccine vector in animals by using a reverse genetics approach. Previously, our group generated a recombinant NDV (LaSota strain) expressing the complete rabies virus G protein (RVG), named rL-RVG. In this study, we constructed the variant rL-RVGTM, which expresses a chimeric rabies virus G protein (RVGTM) containing the ectodomain of RVG and the transmembrane domain (TM) and a cytoplasmic tail (CT) from the NDV fusion glycoprotein to study the function of RVG's TM and CT. The RVGTM did not detectably incorporate into NDV virions, though it was abundantly expressed at the surface of infected BHK-21 cells. Both rL-RVG and rL-RVGTM induced similar levels of NDV virus-neutralizing antibody (VNA) after initial and secondary vaccination in mice, whereas rabies VNA induction by rL-RVGTM was markedly lower than that induced by rL-RVG. Though rL-RVG could spread from cell to cell like that in rabies virus, rL-RVGTM lost this ability and spread in a manner similar to the parental NDV. Our data suggest that the TM and CT of RVG are essential for its incorporation into NDV virions and for spreading of the recombinant virus from the initially infected cells to surrounding cells.

Cyrtorhinus lividipennis Reuter (Hemiptera: Miridae) is an important predatory natural enemy of planthopper and leafhopper eggs in Asian rice paddy fields. Cyrtorhinus lividipennis is known to rely largely on herbivore-induced plant volatiles to identify eggs embedded in rice stem tissues for feeding and on pheromones for mating. However, exactly how C. lividipennis decode these chemical information is unclear. In most insects, the odorant-binding proteins (OBPs) and the chemosensory proteins (CSPs) are essential for seeking out food resources and mates. In this study, we identified 10 OBP and 5 CSP genes in C. lividipennis and investigated their expression patterns in various tissues of adult males and females by quantitative real-time PCR (qRT-PCR). Six OBP genes (ClivOBP1, 2, 4, 6, 9, and 10) were mainly expressed in the male antennae, whereas three genes (ClivOBP3, ClivOBP7, and ClivOBP8) had high expression in the female antennae. ClivCSP1 was predominantly expressed in the male antennae. These findings suggest that most ClivOBPs and ClivCSPs are likely involved in food-searching behavior. The recognition of the pheromone molecules provides the basis for further functional studies on the chemoreception system of C. lividipennis., (© The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To establish type 2 diabetic model in rats complicated with hypertension., Methods: Sixty five SD male rats were divided into normal control group, 1%NaCl water-treated group, 20 mg/kg STZ-1% NaCl-treated group, 30 mg/kg STZ-1%NaCl-treated group and 40 mg/kg STZ-1% NaCl-treated group according to random digit table( n =13).Except that rats in the normal control group were fed with ordinary diet, rats in the other groups were fed with high-fat diet for 4 weeks, then maintained with free access to rat chow and 1% NaCl drinking water for 9 weeks. In addition, rats in streptozotocin(STZ) groups were received STZ at a different dose(20 mg/kg, 30 mg/kg, 40 mg/kg)respectively by intraperitoneal injection at the end of the fourth week. The experimental period lasted 13 weeks. During the study, the general condition, body weight, average food intake, blood glucose, blood pressure, blood lipids and plasma insulin levels of each rat were tested., Results: After STZ injection, tests showed body weight was significantly reduced ( P <0.05), average food intake and fasting/random blood glucose level were increased significantly ( P <0.05); blood pressure was obviously risen ( P <0.05)and the average value of systolic blood pressure was reached 150 mmHg into hypertensive stage at the 4 th week and stable at 150~170 mmHg for five weeks(before the end of experiment); the level of plasma insulin was higher significantly ( P <0.05), the level of plasma triglyceride(TG)was descended significantly ( P <0.05)at the 13 th week of the experimental period, each of which was only in 30 mg/kg STZ-1% NaCl-treated rats and 40 mg/kg STZ-1% NaCl-treated rats as compared with non-treated rats or 1% NaCl water-treated rats., Conclusions: The method that the rat was fed with high-fat diet for 4 weeks, then, received intraperitoneal injection of 30~40 mg/kg STZ combined with feeding 1% NaCl drinking water, which can induce insulin resistance in rats with type 2 diabetes mellitus and hypertension.

The horned toad assemblage, genus Megophrys sensu lato, currently includes three groups previously recognized as the genera Atympanophrys, Xenophrys and Megophrys sensu stricto. The taxonomic status and species composition of the three groups remain controversial due to conflicting phenotypic analyses and insufficient phylogenetic reconstruction; likewise, the position of the monotypic Borneophrys remains uncertain with respect to the horned toads. Further, the diversity of the horned toads remains poorly understood, especially for widespread species. Herein, we evaluate species-level diversity based on 45 of the 57 described species from throughout southern China, Southeast Asia and the Himalayas using Bayesian inference trees and the Generalized Mixed Yule Coalescent (GMYC) approach. We estimate the phylogeny using both mitochondrial and nuclear DNA data. Analyses reveal statistically significant mito-nuclear discordance. All analyses resolve paraphyly for horned toads involving multiple strongly supported clades. These clades correspond with geography. We resurrect the genera Atympanophrys and Xenophrys from the synonymy of Megophrys to eliminate paraphyly of Megophrys s.l. and to account for the morphological, molecular and biogeographic differences among these groups, but we also provide an alternative option. Our study suggests that Borneophrys is junior synonym of Megophrys sensu stricto. We provide an estimation of timeframe for the horned toads. The mitochondrial and nuclear trees indicate the presence of many putative undescribed species. Widespread species, such as Xenophrys major and X. minor, likely have dramatically underestimated diversity. The integration of morphological and molecular evidence can validate this discovery. Montane forest dynamics appear to play a significant role in driving diversification of horned toads., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In plants, sphingolipids, such as long-chain bases (LCBs), act as bioactive molecules in stress responses. Until now, it is still not clear if these lipids are involved in biotic stress responses to herbivore. Herein we report that a rice LCB gene, OsLCB2a1 encoding a subunit of serine palmitoyltransferase (SPT), a key enzyme responsible for the de novo biosynthesis of sphingolipids, plays a critical role in plant defense response to the brown planthopper (BPH) attack and that its up-regulation protects plants from herbivore infestation. Transcripts of OsLCB2a1 gene in rice seedlings were increased at 4 h, but decreased at 8-24 h after BPH attack. Sphingolipid measurement profiling revealed that overexpression of OsLCB2a1 in Arabidopsis thaliana increased trihydroxylated LCB phytosphingosine (t18:0) and phytoceramide by 1.7 and 1.3-fold, respectively, compared with that of wild type (WT) plants. Transgenic Arabidopsis plants also showed higher callose and wax deposition in leaves than that of WT. Overexpression of OsLCB2a1 gene in A. thaliana reduced the population size of green peach aphid ( Myzus persicae ). Moreover, the electrical penetration graph (EPG) results indicated that the aphids encounter resistance factors while reaching for the phloem on the transgenic plants. The defense response genes related to salicylic acid signaling pathway, remained uplgulated in the OsLCB2a1 -overexpressing transgenic plants. Our data highlight the key functions of OsLCB2a1 in biotic stress response in plants.

Validamycin A (Val-A), produced by Streptomyces hygroscopicus 5008 in industrial fermentation, is one of the most widely used anti-fungal agro-antibiotics in Asia and high performance liquid chromatography (HPLC) assay is usually used to determine the production of Val-A. A new approach to determine Val-A by spectrophotometer is developed. During the fermentation of S. hygroscopicus 5008, a pigment secretion was found along with the Val-A biosynthesis. There was a stable relationship between the concentration of Val-A and spectral absorption (SA) value of this pigment at 450 nm, even in different fermentation cultures or conditions. Using SA value as interior label, a rapid spectrophotometric method for determining Val-A production was established. In comparing Val-A productivity by HPLC method with that by SA method, the relative standard deviation (R.S.D.) was 0.007 (less than 0.05, no variation) and the conditional probability [Pr(T < t)] was 0.3491 (greater than 0.05, no difference) at the optimal time point of Val-A fermentation, which demonstrated SA method was as stable and accurate as standard HPLC method. It was applied successfully to finding positive strains with high Val-A productivity and short fermentation time. SA assay is an accurate and cost-effective method for measuring Val-A and screening high-producing strains, and this work provides a new insight for rapid quantitative analysis of antibiotics in fermentation of pigment-producing strains., (Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Background: The residents' knowledge, attitudes and practices related to ambient air pollution and health will help to improve the understanding of environmental protection and make environmental health policies more targeted and effective. This study aimed at knowing the attitudes and behaviors towards ambient air pollution and health., Methods: A cross-sectional survey was conducted in Ningbo, China in January 2015. Personal information and questions pertaining to the knowledge, attitudes and practices towards ambient air pollution and health were collected through questionnaire investigations. Descriptive statistics, chi-square tests and multiple unconditional logistic regression analysis were used., Results: The questionnaire was completed by 1604 respondents (59.41 % women). The awareness rate was 64.59 % and varied significantly with age, levels of education, and occupation (all p < 0.05). Only 5.80 % of the total participants were satisfied with the air quality in Ningbo in 2014. Most respondents (78.80 %) expressed concern about the possible aggravation of the haze. More than 80 % of participants believed that it will take at least 3-5 years or longer before the air quality is improved. Television and internet resources have replaced books and newspapers as the primary sources for obtaining knowledge about haze and related protective measures. 85.22 % of respondents were concerned about air quality index (AQI). Most of the residents have taken protective measures indoors during haze weather. 48.50 % have worn face masks when going outside, the most frequently type of face masks selected were cotton (39.85 %) or gauze face masks (36.24 %). Age and occupation were the main factors associated with the level of knowledge about air pollution (p < 0.05)., Conclusions: There were a relatively high knowledge awareness rate, strong health protection consciousness and high enthusiasm for air pollution control among Ningbo residents. The elderly people and less-educated residents are the targetable population for improving environment.

Validamycin A (Val-A) synthesized by Streptomyces hygroscopicus 5008 is widely used as a high-efficient antibiotic to protect plants from sheath blight disease. A novel fermentation strategy was introduced to stimulate Val-A production by adding oxygen carriers. About 58 % increase in Val-A production was achieved using liquid paraffin. Further, biomass, carbon source, metabolic genes, and metabolic enzymes were studied. It was also found that the supplementation of liquid paraffin increased the medium dissolved oxygen and intracellular oxidative stress level. The expression of the global regulators afsR and soxR sensitive to ROS, ugp catalyzing synthesis of Val-A precursor, and Val-A structural genes was enhanced. The change of the activities of glucose-6-phosphate dehydrogenase and glyceraldehyde 3-phosphate dehydrogenase was observed, which reflected the redirection of carbon metabolic flux. Based on these results, liquid paraffin addition as an oxygen carrier could be a useful technique in industrial production of Val-A and our study revealed a redox-based secondary metabolic regulation in S. hygroscopicus 5008, which provided a new insight into the regulation of the biosynthesis of secondary metabolites.

The rice water weevil, Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae), is a serious pest species both in its original distribution region of northern America and its invaded regions of eastern Asia and southern Europe. The odorant-binding proteins (OBPs) and the chemosensory proteins (CSPs) play important roles in host and mate locating, thus might play a significant role in the success of the species as an invader, which has not been characterized yet. We identified 10 OBPs and 5 CSPs in L. oryzophilus and investigated the expression profiles of these genes in various tissues by quantitative real-time PCR. Five classic OBPs were predominantly expressed in the antennae. CSPs were expressed ubiquitously with particularly high transcript levels in antennae, legs, and wings. Three antenna-specific OBPs (LoOBP1, 8, 11) were up-regulated following 1-3 d of food deprivation and down-regulated afterward. These findings suggest most classic OBPs are likely involved in chemoreception whereas CSPs as well as the minus-C OBPs may have broader physiological functions, which in turn may help to understand the molecular aspects of chemical communication in this invasive insect., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

True frogs of the genus Rana are widely used as model organisms in studies of development, genetics, physiology, ecology, behavior, and evolution. Comparative studies among the more than 100 species of Rana rely on an understanding of the evolutionary history and patterns of diversification of the group. We estimate a well-resolved, time-calibrated phylogeny from sequences of six nuclear and three mitochondrial loci sampled from most species of Rana, and use that phylogeny to clarify the group's diversification and global biogeography. Our analyses consistently support an "Out of Asia" pattern with two independent dispersals of Rana from East Asia to North America via Beringian land bridges. The more species-rich lineage of New World Rana appears to have experienced a rapid radiation following its colonization of the New World, especially with its expansion into montane and tropical areas of Mexico, Central America, and South America. In contrast, Old World Rana exhibit different trajectories of diversification; diversification in the Old World began very slowly and later underwent a distinct increase in speciation rate around 29-18 Ma. Net diversification is associated with environmental changes and especially intensive tectonic movements along the Asian margin from the Oligocene to early Miocene. Our phylogeny further suggests that previous classifications were misled by morphological homoplasy and plesiomorphic color patterns, as well as a reliance primarily on mitochondrial genes. We provide a phylogenetic taxonomy based on analyses of multiple nuclear and mitochondrial gene loci. [Amphibians; biogeography; diversification rate; Holarctic; transcontinental dispersal., (© The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Six lactic acid bacterial (LAB) strains were isolated from traditionally fermented Xinjiang cheese and evaluated for functional and probiotic properties and potentials as starter cultures. The isolated six LAB strains comprised Lactobacillus rhamnosus (one strain), Lactobacillus helveticus (one strain), and Enterococcus hirae (four strains). All of the six strains were tolerant to acidic and bile salt conditions. Among which, the L. rhamnosus R4 strain showed more desirable antimicrobial, auto-aggregation, and hydrophobic activity. In addition, the strain L. rhamnosus R4 exhibited the highest level of free radical scavenging activity (53.78% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and 45.79% of hydroxyl radicals). L. rhamnosus R4 also demonstrated cholesterol and triglyceride degradation by 50.97% and 28.92%, respectively. To further examine the health-promoting effects of these LAB strains on host lifespan, Caenorhabditis elegans was used as an in vivo model. Worms fed LAB as a food source had significant differences in lifespan compared to those fed Escherichia coli OP50 (as a negative control). Feeding of L. rhamnosus R4 extended the mean lifespan of C. elegans by up to 36.1% compared to that of the control. The results suggest that the strains isolated from Xinjiang fermented dairy products have high potential as starter cultures in the cheese industry.

Alzheimer's disease (AD) is characterized by memory loss, intracellular neurofibrillary tangles, and extracellular plaque deposits composed of β-amyloid (Aβ). Previous reports showed that naturally occurring autoantibodies, such as intravenous immunoglobulin (IVIG), benefited patients with moderate-stage AD who carried an APOE-ε4 allele. However, the mechanism underlying the role of IVIG remains unclear. In this study, we identified naturally occurring autoantibodies against Aβ oligomers (NAbs-Aβo), which were purified by Aβ42 oligomer or Cibacron Blue affinity chromatography from IVIG and termed as Oli-NAbs and Blue-NAbs, respectively. Oli-NAbs and Blue-NAbs recognized Aβ42 oligomers or both Aβ40 and 42 oligomers, differently. Both antibodies inhibited Aβ42 aggregation and attenuated Aβ42-induced cytotoxicity. Compared with vehicles, Oli-NAbs, Blue-NAbs and IVIG significantly improved the memory and cognition, and reduced the soluble and oligomeric Aβ levels in APPswe/PS1dE9 transgenic mice. Further investigation showed that Blue-NAbs at increased doses effectively decreased plaque burden and insoluble Aβ levels, whereas Oli-NAbs significantly declined the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines in vivo. Therefore, high levels of these antibodies against oligomeric Aβ40 or Aβ42 were required, correspondingly, to achieve the optimal effect. NAbs-Aβo could be condensed to a high concentration by affinity chromatography and its isolation from IVIG may not interfere with the normal function of conventional IVIG as its concentration is very low. Thus, the isolated NAbs-Aβo as an extra product of plasma required low cost and the enriched NAbs-Aβo may be more feasible than IVIG for the treatment of AD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of the present study is to examine the expression level of peripheral mir-21 in multiple myeloma (MM) patients and to determine its clinical significance. MM patients (30), monoclonal gammopathy of undetermined significance (MGUS) patients (14), and normal controls (20) were recruited to determine the serum level of β2-MG, IgA and IgM, IgG, λ, κ, TP, ALB, Hb, LDH, and Ca(2+). Gene expression of mir-21 was quantified by SYBR green real-time fluorescent quantitative PCR. We found that the expression level of serum mir-21 in the MM group was significantly higher than the MGUS group and the NC group (P < 0.01). According to the ISS installment, the level of mir-21, lgG, κ, and ALB in the MM group in stage I differed from that in stages II and III. The level of IgA, β2-MG in stage III was higher as compared with stage I and II (P < 0.05 and P < 0.01).The levels of mir-21, κ, (κ+λ), IgG, (IgG + IgA + IgM), and β2-MG in MM patients were positively correlated with ALB (P < 0.01). Based on the results, miR-21 plays an important role as an oncogene. Mir-21 may be important in the occurrence, development, and disease prognosis of MM.

Recent evidence showed that amylin deposition is not only found in the pancreas in type 2 diabetes mellitus (T2DM) patients, but also in other peripheral organs, such as kidneys, heart and brain. Circulating amylin oligomers that cross the blood-brain barrier and accumulate in the brain may be an important contributor to diabetic cerebral injury and neurodegeneration. Moreover, increasing epidemiological studies indicate that there is a significant association between T2DM and Alzheimer's disease (AD). Amylin and β-amyloid (Aβ) may share common pathophysiology and show strikingly similar neurotoxicity profiles in the brain. To explore the potential effects of rutin on AD, we here investigated the effect of rutin on amylin aggregation by thioflavin T dyeing, evaluated the effect of rutin on amylin-induced neurocytotoxicity by the MTT assay, and assessed oxidative stress, as well as the generation of nitric oxide (NO) and pro-inflammatory cytokines in neuronal cells. Our results showed that the flavonoid antioxidant rutin inhibited amylin-induced neurocytotoxicity, decreased the production of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), malondialdehyde (MDA) and pro-inflammatory cytokines TNF-α and IL-1β, attenuated mitochondrial damage and increased the GSH/GSSG ratio. These protective effects of rutin may have resulted from its ability to inhibit amylin aggregation, enhance the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and reduce inducible nitric oxide synthase (iNOS) activity. These in vitro results indicate that rutin is a promising natural product for protecting neuronal cells from amylin-induced neurotoxicity and oxidative stress, and rutin administration could be a feasible therapeutic strategy for preventing AD development and protecting the aging brain or slowing neurodegenerative processes.