Diversity of Arbuscular Mycorrhizal Fungi of the Rhizosphere of Lycium barbarum L. from Four Main Producing Areas in Northwest China and Their Effect on Plant Growth.

Arbuscular mycorrhizal fungi (AMF) can help plants absorb more mineral nutrients after they colonize plant roots, and the mycelia harmonize the soil structure and physical and chemical properties by secreting compounds. AMF species co-evolve with their habitat's geographic conditions and hosts; this gradually causes differences in the AMF species. By using Melzer's reagent to analyze the morphology and using Illumina Miseq sequencing technology to perform the molecular identification of AMF communities among the four typical L. barbarum planting areas (Zhongning, Guyuan, Jinghe, and Dulan) investigated, the variety of L. barbarum roots and rhizosphere AMF communities was greater in the Zhongning area, and every region additionally had endemic species. The successfully amplified AMF was re-applied to the L. barbarum seedlings. We found that the total dry weight and accumulation of potassium increased significantly (p < 0.05), and the root volume and number of root branches were significantly higher in the plants that were inoculated with Paraglomus VTX00375 in the pot experiment, indicating that AMF improves root development and promotes plant growth. We have investigated AMF germplasm species in four regions, and we are committed to the development of native AMF resources. The multiplication and application of AMF will be conducive to realizing the potential role of biology in the maintenance of agroecology.

Single-cell RNA-seq and single-cell bisulfite-sequencing reveal insights into yak preimplantation embryogenesis.

Extensive epigenetic reprogramming occurs during preimplantation embryonic development. However, the impact of DNA methylation in plateau yak preimplantation embryos and how epigenetic reprogramming contributes to transcriptional regulatory networks are unclear. In this study, we quantified gene expression and DNA methylation in oocytes and a series of yak embryos at different developmental stages and at single-cell resolution using single-cell bisulfite-sequencing and RNA-seq. We characterized embryonic genome activation and maternal transcript degradation and mapped epigenetic reprogramming events critical for embryonic development. Through cross-species transcriptome analysis, we identified 31 conserved maternal hub genes and 39 conserved zygotic hub genes, including SIN3A, PRC1, HDAC1/2, and HSPD1. Notably, by combining single-cell DNA methylation and transcriptome analysis, we identified 43 candidate methylation driver genes, such as AURKA, NUSAP1, CENPF, and PLK1, that may be associated with embryonic development. Finally, using functional approaches, we further determined that the epigenetic modifications associated with the histone deacetylases HDAC1/2 are essential for embryonic development and that the deubiquitinating enzyme USP7 may affect embryonic development by regulating DNA methylation. Our data represent an extensive resource on the transcriptional dynamics of yak embryonic development and DNA methylation remodeling, and provide new insights into strategies for the conservation of germplasm resources, as well as a better understanding of mammalian early embryonic development that can be applied to investigate the causes of early developmental disorders.

Translocation of IGF-1R in endoplasmic reticulum enhances SERCA2 activity to trigger Ca2+ER perturbation in hepatocellular carcinoma.

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rß is translocated into the ER by ß-arrestin2 (ß-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rß. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rß levels. ER IGF-1Rß phosphorylates SERCA2 on Tyr990 to enhance its activity. Mutation of SERCA2-Tyr990 disrupted the interaction of ER IGF-1Rß with SERCA2, and therefore ER IGF-1Rß failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca2+ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rß and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca2+ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr990 in HCC.

Efficacy of Dietary Intervention with Group Activities on Dietary Intakes, Frailty Status, and Working Memory: A Cluster-Randomized Controlled Trial in Community Strongholds.

Geriatric community centers often offer nutrition lectures to older adults. In order to make learning more interesting and pragmatic, we developed group activity sessions. This undertaking was tested for its efficacy in changes of frailty status and several other geriatric health parameters. A cluster-randomized controlled trial was conducted between September 2018 and December 2019 at 13 luncheon-providing community strongholds in Taipei, Taiwan. During the 3-month intervention period, 6 experimental strongholds received a weekly 1 h exercise workout and 1 h nutrition activities aiming at achieving the recommendations of the Taiwanese Daily Food Guide for elderlies; the other 7 received a weekly 1 h exercise workout and 1 h other activities. Dietary intakes and frailty status were the primary outcomes. Secondary outcomes included working memory and depression. The measurements were performed at baseline, 3 months, and 6 months. The nutrition intervention significantly reduced the intake of refined grains and roots (p = 0.003) and increased that of non-refined grains and roots (p = 0.008), dairy products (p < 0.0001), and seeds and nuts (at borderline, p = 0.080) at 3 months. Some, but not all, of these changes were maintained at 6 months. Performance improvements included the frailty status score (p = 0.036) and forward digit span (p = 0.004), a working memory parameter, at 3 months. Only the forward digit span remained improved (p = 0.007) at 6 months. The 3-month nutrition group activities combined with exercise sessions improved the frailty status and working memory more than exercise alone. The dietary and frailty improvements were accompanied by improved dietary intakes and advanced behavioral stages. However, the improved frailty status backslid after intervention ceased, suggesting that boosting activities are needed for maintaining the intervention effect.

The color stability, water sorption, and solubility of ten composite resins.

OBJECTIVES: This study aims to evaluate the color stability and related properties including water sorption and solubility of ten light-cured composite resins in different solutions. METHODS: A total of 10 composite resins were BeautifilⅡ(B2) and Ceram. X One Universal (CXU), Charisma (CS), Charisma Diamond (CD), Denfil (DF), DX. Universal (DXU), Filtek Z250 (Z250), Filtek Z350 XT (Z350), FS-1 (FS), and Magnafill Putty (MP). Meanwhile, a total of 20 disk-shaped samples were fabricated and randomly divided into four groups (n=5), which were immersed in distilled water (control group), curry, coffee, and red wine for 28 days. The color (CIE L∗a∗b∗) was measured by a spectrophotometer at baseline and 1, 7, 14, 21, and 28 days after immersion, and the color differences were calculated. Water sorption and solubility values were measured ba-sed on ISO 4049: 2019. In addition, three-way ANOVA was used to evaluate the influence of resin materials, solutions, and immersion time on discoloration results, meanwhile, one-way ANOVA was used to compare the water sorption values and solubility values of different materials. RESULTS: All samples showed a certain degree of color change with time. Color differences were significantly influenced by materials, solutions, and immersion time (P<0.001). The color changes of the measured materials at any time point: curry>red wine>coffee>distilled water. Thus, all materials showed clinically unacceptable discoloration (ΔE>3.3) after immersing in staining curry, coffee, and red wine for 7 days. Therefore, when immersed in curry for 28 days, CS and DXU had the smallest and the largest color difference. In addition, when immersed in coffee for 28 days, FS showed the smallest color change and DXU showed the largest. Moreover, when immersed in red wine for 28 days, FS showed the smallest color change and Z350 showed the largest. Furthermore, MP and CXU had small color differences in all solutions. Meanwhile, Z350 had the highest water sorption and MP had the lowest. The solubility values of CS and CD were significantly higher than those of other materials. CONCLUSIONS: The color stability of light-cured composite resin is materials-depended and affected by pigment types and immersion time. Thus, MP and CXU have better color stability. MP has low water sorption.

Evaluation of the Color Stability, Water Sorption, and Solubility of Current Resin Composites.

This study aims to assess the color stability, water sorption, and solubility of 11 resin composites as commercially available dental products. Twenty samples (10 mm in diameter and 2 mm in thickness) of each material were fabricated using a customized silicone mold, followed by immersion in each of curry, coffee, wine, and distilled water for 28 days (n = 5). Baseline shade and color changes (ΔE) were measured using a reflection spectrophotometer. The CIE L*, a*, b* system was used to evaluate the color changes. Five samples of each resin composite were applied to test water sorption and solubility according to ISO 4049:2009. As a result, the ∆E values were significantly influenced by each of the three factors (composition of material, solution, time) and the interactions between them (p < 0.001). Highest resistance to discoloration was achieved by Ceram.X One Universal (CXU), followed by Magnafill Putty (MP). Generally, microhybrid composites showed fewer color changes than nanohybrid composites and giomers. DX. Universal and Filtek Z350 XT showed the highest ΔE values in all colorants. All materials tested in this study fulfilled the criteria of ISO 4049:2009; CXU and MP had the lowest water sorption and solubility. The Pearson test showed statistically significant positive correlations between water sorption and ΔE and between solubility and ΔE.

Sex Differences in Dietary Patterns of Adults and Their Associations with the Double Burden of Malnutrition: A Population-Based National Survey in the Philippines.

A dietary pattern transition is a risk factor for the double burden of malnutrition (DBM), but related information is limited. This study aimed to identify sex differences in dietary patterns of adults in a low-middle income country and to examine their association with DBM. A total of 8957 adults (4465 men and 4492 non-pregnant and non-lactating women) who participated in the 2013 Philippine National Nutrition Survey were included in the analysis. Logistic regression models were formulated to investigate the relationship between dietary patterns and DBM. The factor analysis derived seven dietary patterns for males and six patterns for females. Results showed that approximately 30% of Filipino adults suffered from DBM. The rice pattern was associated with lower odds of DBM for males only. The meat and sugar pattern in males and the protein-rich foods, cereal, and sugar pattern in females decreased DBM likelihood. An inverse relationship was observed for the vegetables and corn patterns, wherein females had an increased risk for DBM. Our findings suggest that rice-based and meat-containing patterns could play protective roles in DBM development among adults in the Philippines. Understanding sex-specific dietary patterns can be utilized to guide public health nutrition interventions in the prevention of malnutrition in all its forms.

[Molecular mechanism of Spatholobi Caulis in treatment of lung cancer based on network pharmacology and molecular docking].

In this paper, the molecular mechanism of Spatholobi Caulis in the treatment of non-small cell lung cancer(NSCLC) was studied through network pharmacology and molecular docking analysis. With traditional Chinese medicine(TCM) Spatholobi Caulis as the study object, active ingredients of Spatholobi Caulis and corresponding potential drug targets were obtained from Traditio-nal Chinese Medicine Pharmacology Platform(TCMSP) database; GeneCards database was used to collect cancer-related genes; Cytoscape software was used to build Spatholobi Caulis active ingredient-target-pathway relationship network. DAVID database was used for GO and KEGG enrichment analysis of targets, KEGG signaling pathway was visualized, and compounds were screened out for molecular docking. Finally, in vitro experiments on human lung cancer cells, A549 treated with luteolin and licochalcone A were used to preliminarily verify the core targets and pathways, cell proliferation was detected by CCK-8 method, and expressions of caspase-3 and Bax protein were detected by Western blot. A total of 23 active components and 170 potential drug targets were selected from Spatholobi Caulis, involving 127 pathways in total. Molecular docking results showed that licochalcone A,(Z)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxy-phenyl) ethyl] acrylamide, consumeclose grain successfully docked with the key target EGFR, and binding energy of the three compounds was less than-5 kcal·mol~(-1). CCK-8 results showed that luteolin, licochalcone A, and Spatholobi Caulis extract had the inhibitory effect on human lung cancer A549 cells. Western blot showed that luteolin, licochalcone A and Spatholobi Caulis extract could induce cell apoptosis by increasing the expressions of pro-apoptotic factors caspase-3 and Bax. In this study, the anti-lung cancer effect of Spatholobi Caulis was studied through network pharmacology and molecular docking, in order to provide ideas for the molecular mechanism of Spatholobi Caulis in the treatment of lung cancer.

Lead exposure activates the Nrf2/Keap1 pathway, aggravates oxidative stress, and induces reproductive damage in female mice.

Lead, a common metallic contaminant, is widespread in the living environment, and has deleterious effects on the reproductive systems of humans and animals. Although numerous toxic effects of lead have been reported, the effects and underlying mechanisms of the impacts of lead exposure on the female reproductive system, especially oocyte maturation and fertility, remain unknown. In this study, mice were treated by gavage for seven days to evaluate the reproductive damage and role of Nrf2-mediated defense responses during lead exposure. Lead exposure significantly reduced the maturation and fertilization of oocytes in vivo. Additionally, lead exposure triggered oxidative stress with a decreased glutathione level, increased amount of reactive oxygen species, and abnormal mitochondrial distribution. Moreover, lead exposure caused histopathological and ultrastructural changes in oocytes and ovaries, along with decreases in the activities of catalase, glutathione peroxidase, total superoxide dismutase, and glutathione-S transferase, and increases in the levels of malonaldehyde in mouse ovaries. Further experiments demonstrated that lead exposure activated the Nrf2 signaling pathway to protect oocytes against oxidative stress by enhancing the transcription levels of antioxidant enzymes. In conclusion, our study demonstrates that lead activates the Nrf2/Keap1 pathway and impairs oocyte maturation and fertilization by inducing oxidative stress, leading to a decrease in the fertility of female mice.

Pomegranate flower extract bidirectionally regulates the proliferation, differentiation and apoptosis of 3T3-L1 cells through regulation of PPARγ expression mediated by PI3K-AKT signaling pathway.

OBJECTIVES: Pomegranate flower is a kind of uygur medicine with anti - type 2 diabetes, anti - lipid, anti - inflammation, anti - oxidation. We investigated the effect of pomegranate flower extract (PFE) on the proliferation, differentiation and apoptosis of 3T3-L1 preadipocytes, as well as the effects of five compounds in PF on cell differentiation. METHODS: 3T3-L1 preadipocytes were treated with PFE (0.5, 1, 2, 5, 10, 20, 50, 100 µg/mL), quercetin, luteolin, ursolic acid, apigenin and kaempferol (5, 10, 20, 40, 80 µM), and cell viability was measured at 24, 48 and 72 h by Cell Counting Kit-8. The modified cocktail induction method induced the differentiation of 3T3-L1 preadipocytes, and treated them with PFE and the compounds. The lipid accumulation was determined by oil red O staining, and the intracellular triglyceride content was determined by commercial kit. The expressions of PPARγ, C/EBP, LPL, DGAT and aP2 mRNA in mature adipocyte were determined by q-PCR, and the expressions of PPARγ, Akt, p-akt and PI3K protein were determined by western blot. 3T3-L1 preadipocytes were treated with PFE (5, 10, 20 µg/mL) while induced apoptosis by palmitate (300 µM), Hoechst staining to observe apoptosis morphology, Annexin Ⅴ- FITC/PI staining with flow cytometry instrument to detect the number of early and late apoptosis cells, the q-PCR and western blot for determining the Bcl-2, Bax, caspase 3 mRNA and protein expression. RESULTS: PFE (5, 10, 20 µg/mL) promoted or did not affect the proliferation and differentiation of 3T3-L1 preadipocytes, and reduced the number of early and late apoptotic cells, increased the expression of Bcl-2 mRNA and protein, and inhibited the expression of Bax and caspase-3 mRNA and protein. Furthermore, PFE (40, 60 µg/mL), quercetin (10, 20, 40 µM), luteolin (5, 10, 20 µM), apigenin(20,40 µM), kaempferol (20, 40 µM) significantly restrain the 3T3-L1 different extent proliferation and differentiation of preadipocyte, reduce the accumulation of lipids in adipocyte, reduce expression of adipogenesis factor, PFE(40, 60 µg/mL) inhibited the activation of the PI3K-Akt pathway by inhibiting the expression of PI3K and p-Akt proteins, and inhibited preadipocyte differentiation by reduce the expression of PPARγ protein. CONCLUSION: PFE has a concentration-related bidirectional effect on the proliferation, differentiation and apoptosis of 3T3-L1 preadipocytes, which depends on the regulation of PI3K-Akt pathway, which is of guiding role for PFE in the treatment of type 2 diabetes, hyperlipidemia, obesity and other diseases.

CARM1 is heterogeneous in mouse four-cell embryo and important to blastocyst development.

Coactivator-associated arginine methyltransferase 1 (CARM1) is a type I arginine methyltransferase that methylates the arginine residues of histone and nonhistone. Carm1 regulates various cellular processes, including transcriptional regulation, mRNA processing, cellular proliferation, and differentiation. Blastomeres with high Carm1 expression levels show cleavage tendency to inner cell mass (ICM) in mouse embryos. However, details about the factors for CARM1 distribution in mouse early embryos and the role of Carm1 in blastocyst development remain unclear. Here, the endonuclear distribution of CARM1 protein was heterogeneous between blastomeres from the late four-cell stage to the blastocyst stage. The heterogeneity of CARM1 distribution in blastomeres at the late four-cell stage was randomly obtained from two-cell stage embryos. From the four-cell stage to morula, CARM1 in individual blastomere remained heterogeneous. In the blastocyst stage, CARM1 protein level in ICM was much higher than that in trophoblast. We found that microRNA (miRNA) miR-181a is an important regulator for Carm1 distribution at the late four-cell stage. The ratio of heterogeneous embryos was reduced in all the embryos when miR-181a was inhibited. CARM1 inhibition reduced the level of symmetrical histone H3 arginine-26 dimethylation and impaired blastocyst development. Silencing Carm1 reduced cell number and increased cell apoptosis at the blastocyst stage. These results show a CARM1 heterogeneous distribution from the four-cell embryos to the blastocysts. miR-181a regulates the control of CARM1 heterogeneous distribution in the four-cell-stage embryos, and CARM1 is an important protein in regulating blastocyst development.

Ochratoxin A exposure causes meiotic failure and oocyte deterioration in mice.

Ochratoxin A (OTA) is a mycotoxin produced by fungi and occurs naturally in various foodstuffs and some animal-derived products. This mycotoxin can cause deleterious effects on kidney, liver, central nervous, and immune system. However, potential mechanisms regarding how OTA disrupts the mammalian oocyte quality have not been clearly defined. In this study, we proved that OTA weakened oocyte quality by impairing oocyte meiotic maturation. We found that female mice treated with 1 mg/kg body weight OTA by intraperitoneal (IP) injection for 7 days displayed ovarian dysfunction and decreased offspring number. We also found that OTA treatment at 7.5 µM for 16 h decreased the rate of first polar body extrusion by disrupting spindle and chromosome alignment. In addition, OTA caused oxidative stress by inducing the accumulation of reactive oxygen species and consumption of antioxidants during meiosis, consequently resulting in oocytes apoptosis. Mitochondrial damage and insufficient energy supply were also observed in OTA-pretreated oocytes, which led to the meiotic failure of oocyte. Moreover, the epigenetic modifications were also affected, showing with altered 5 mC, 5hmC, H3K9ac, and H3K9me3 levels in mice oocytes. In summary, these results showed that OTA could decrease oocyte maturation and fertility by inducing oxidative stress and epigenetic changes.

Reproductive toxicity of acute Cd exposure in mouse: Resulting in oocyte defects and decreased female fertility.

Cadmium (Cd), a known metal contaminant, is widespreadly used in industry, thereby human health is severely affected through the way of occupational and environmental exposure. The adverse effects of the exposure to Cd on the female reproductive system, especially oocyte maturation and fertility have not been clearly defined. In this study, we found the arrested development of ovaries and uteri after Cd exposure and determined oocyte quality via assessing the key regulators during meiotic maturation and fertilization. We found that Cd exposure impeded the mouse oocyte meiotic progression by disrupting the normal spindle assembly, chromosome alignment and actin cap formation. Besides, exposure to Cd induced oxidative stress with the increased reactive oxygen species and apoptosis levels, leading to abnormal mitochondrial distribution, insufficient energy supply, and DNA damage, which ultimately led to oocyte quality deterioration. We also analyzed the effects of cadmium on epigenetic modifications, and the levels of 5mC, H3K9me3 and H3K9ac decreased after acute exposure to cadmium. Further experiments showed that the litter size in Cd-exposed female mice reduced, thereby indicating increased reproductive Cd toxicity. In conclusion, Cd exposure impairs oocyte maturation and fertilization ability induced by oxidative stress, early apoptosis and epigenetic modifications, which lead to the decrease of female fertility.

Erratum: Cheng, Y.; Zhao, C.; Zhang, J.; Wu, Z. Application of a Novel Long-Gauge Fiber Bragg Grating Sensor for Corrosion Detection via a Two-Level Strategy. Sensors 2019, 19, 954.

The authors wish to make the following erratum to this paper [...].

Application of a Novel Long-Gauge Fiber BraggGrating Sensor for Corrosion Detection via aTwo-level Strategy.

Corrosion of main steel reinforcement is one of the most significant causes of structuraldeterioration and durability reduction. This research proposes a two-level detection strategy tolocate and quantify corrosion damage via a new kind of long-gauge fiber Bragg grating (FBG) sensor.Compared with the traditional point strain gauges, this new sensor has been developed for bothlocal and global structural monitoring by measuring the averaged strain within a long gauge length.Based on the dynamic macrostrain responses of FBG sensors, the strain flexibility of structures areidentified for corrosion locating (Level 1), and then the corrosion is quantified (Level 2) in terms ofreduction of sectional stiffness of reinforcement through the sensitivity analysis of strain flexibility.The two-level strategy has the merit of reducing the number of unknown structural parametersthrough corrosion damage location (Level 1), which guarantees that the corrosion quantification(Level 2) can be performed efficiently in a reduced domain. Both numerical and experimentalexamples have been studied to reveal the ability of distributed long-gauge FBG sensors for corrosionlocalization and quantification.

Plasticizer Bis(2-ethylhexyl) Phthalate Causes Meiosis Defects and Decreases Fertilization Ability of Mouse Oocytes in Vivo.

Bis(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer in polyvinyl chloride (PVC) plastics. Humans and animals are widely and continuously exposed to DEHP, especially with respect to diet, which is associated with reproductive diseases. Nevertheless, the effects and underlying mechanisms of DEHP exposure on oocytes in vivo remain ambiguous. In this study, we found that oral administration of DEHP (40 µg/kg body weight per day for 14 days) markedly reduced the maturation and fertilization of oocytes in vivo. In addition, DEHP caused oxidative stress, increased reactive oxygen species generation, promoted early apoptosis, and resulted in DNA damage in mouse oocytes. Moreover, DEHP exposure caused mitochondrial damage, reduced ATP content, down-regulated actin expression, and disturbed the spindle assembly and chromosome alignment in mouse oocytes. Furthermore, DEHP exposure remarkably impaired the localization and protein level of Juno, the sperm receptor on the membrane of oocytes. The levels of DNA methylation, H3K9me3, and H3K9ac were also altered in the DEHP-exposed mouse oocytes. Thus, our results indicated that DEHP exposure reduced the maturation and fertilization capabilities of mouse oocytes by affecting cytoskeletal dynamics, oxidative stress, early apoptosis, meiotic spindle morphology, mitochondria, ATP content, Juno expression, DNA damage, and epigenetic modifications in mouse oocytes.

Melatonin supplementation during in vitro maturation of oocyte enhances subsequent development of bovine cloned embryos.

Oocyte quality, which is directly related to reprogramming competence, is a major important limiting factor in animal cloning efficiency. Compared with oocytes matured in vivo, in vitro matured oocytes exhibit lower oocyte quality and reprogramming competence primarily because of their higher levels of reactive oxygen species. In this study, we investigate whether supplementing the oocyte maturation medium with melatonin, a free radical scavenger, could improve oocyte quality and reprogramming competence. We found that 10-9 M melatonin effectively alleviated oxidative stress, markedly decreased early apoptosis levels, recovered the integrity of mitochondria, ameliorated the spindle assembly and chromosome alignment in oocytes, and significantly promoted subsequent cloned embryo development in vitro. We also analyzed the effects of melatonin on epigenetic modifications in bovine oocytes. Melatonin increased the global H3K9 acetylation levels, reduced the H3K9 methylation levels, and minimally affected DNA methylation and hydroxymethylation. Genome-wide expression analysis of genes in melatonin-treated and nontreated oocytes was also conducted by high-throughput RNA sequencing. Our results indicated that melatonin ameliorates oocyte oxidative stress and improves subsequent in vitro development of bovine cloned embryos.

SOX4 transcriptionally regulates multiple SEMA3/plexin family members and promotes tumor growth in pancreatic cancer.

Semaphorin signaling through Plexin frequently participates in tumorigenesis and malignant progression in various types of cancer. In particular, the role of semaphorin signaling in pancreatic ductal adenocarcinoma (PDAC) remains unexplored, despite a high likelihood of metastasis and mortality. Unlike other epithelial malignancies that often express a small number of specific genes in the Semaphorin/Plexin family, five or more are often expressed in human PDAC. Such concomitant expression of these SEMA3/Plexin family members is not a result of gene amplification, but (at least partially) from increased gene transcription activated by SOX4 de novo expressed in PDAC. Via chromatin-immunoprecipitation, luciferase promoter activity assay and electrophoresis mobility shift assay, SOX4 is demonstrated to bind to the consensus site at the promoter of each SEMA3 and Plexin gene to enhance transcription activity. Conversely, RNAi-knockdown of SOX4 in PDAC cell lines results in decreased expression of SEMA3/Plexin family members and is associated with restricted tumor growth both in vitro and in SCID mice. We further demonstrate that SOX4 levels parallel with the summed expression of SEMA3/Plexin family members (P = 0.033, NPar Kruskal-Wallis one-way analysis), which also correlates with poor survival in human PDAC (P = 0.0409, Kaplan-Meier analysis). Intriguingly, miR-129-2 and miR-335, both of which target SOX4 for degradation, are co-repressed in human PDAC cases associated with up-regulated SOX4 in a statistically significant way. In conclusion, we disclose a miR-129-2(miR-335)/SOX4/Semaphorin-Plexin regulatory axis in the tumorigenesis of pancreatic cancer.

Reaching Asian Americans: sampling strategies and incentives.

Reaching and recruiting representative samples of minority populations is often challenging. This study examined in Chinese and Korean Americans: 1) whether using two different sampling strategies (random sampling vs. convenience sampling) significantly affected characteristics of recruited participants and 2) whether providing different incentives in the mail survey produced different response rates. We found statistically significant, however mostly not remarkable, differences between random and convenience samples. Offering monetary incentives in the mail survey improved response rates among Chinese Americans, while offering a small gift did not improve response rates among either Chinese or Korean Americans. This information will be useful for researchers and practitioners working with Asian Americans.

[Liangge san effects the expression of CD14 and scaverger receptor in the Kupffer cells of liver of endotoxemia mice].

OBJECTIVE: To study the effects of Liangge San to the expression of CD14 and scaverger receptor(SR) in the kupffer cells of liver and the pathological changes of liver tissue of endotoxemia-mice. METHOD: The model was established with intravenous injection of lipopolysaccharide (LPS) and at the same time different dose Liangge San were given. The expression of CD14 and scaverger receptor were detected with immunohigtochemistry at the 2nd, 4th, 8th hour ofter injury and analyzed with computer image system, and the pathological changes of liver tissue were also observed. RESULT: At the three different hours, the expression of CD14 and scaverger receptor in macrophages of liver of LPS-injury group showed significant increase and significant decrease respectively, compared with that of the blank-control group (P < 0.01). The expression in dexamethasone group and Liangge San different dose groups were intermediate between those in injury group and those in control group. Compared with expression of LPS-injury group, those of dexamethasone group and Liangge San different dose groups showed significant differences (P < 0.01), especially that of Liangge San high dose group. Liver cells showed vacuole change. Changes of CD14 and SR expression were paralleled with the severity of liver damages of the mice. CONCLUSION: Liangge San can inhibite the up-regulation of CD14 expression and down-regulation of scaverger receptor expression in a dosage-dependent manner and also alleviate the damages of liver induced by LPS.