The importance of the cell surface receptor CXCR4 and the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is well-established in normal and malignant hematopoiesis. The Protein Epitope Mimetic POL5551 is a novel and potent antagonist of CXCR4. POL5551 efficiently mobilizes hematopoietic stem and progenitor cells, but its effects in acute lymphoblastic leukemia (ALL) have not been reported. Here, we demonstrate that POL5551 is a potent antagonist of CXCR4 in pre-B and T cell ALL cell lines and pediatric ALL primary samples. POL5551 has activity at nanomolar concentrations in decreasing CXCR4 antibody binding, blocking SDF-1α-mediated phosphorylation of ERK1/2, inhibiting SDF-1α-induced chemotaxis, and reversing stromal-mediated protection from chemotherapy. POL5551 is significantly more effective at inhibiting CXCR4 antibody binding than the FDA-approved CXCR4 inhibitor plerixafor in ALL cell lines and primary samples. We also show that treatment with POL5551 in vitro and cytarabine +/- POL5551 in vivo modulates surface expression of adhesion molecules, findings that may guide the optimal clinical use of POL5551. Finally, we demonstrate that POL5551 increases sensitivity to cytarabine in a xenograft model of a high-risk pediatric ALL, infant MLL-rearranged (MLL-R) ALL. Therefore, disruption of the CXCR4/SDF-1 axis with POL5551 may improve outcomes in children with high-risk ALL.

This study aims to investigate the effect of miR-10b overexpression on cancer cell proliferation, migration, invasion, and Hoxd10 expression.

Because of its high pathogenicity and infectivity, tuberculosis is a serious threat to human health. Some information about the functions of the genes in Mycobacterium tuberculosis genome was currently available, but it was not enough to explore transcriptional regulatory mechanisms. Here, we applied the WGCNA (Weighted Gene Correlation Network Analysis) algorithm to mine pooled microarray datasets for the M. tuberculosis H37Rv strain. We constructed a co-expression network that was subdivided into 78 co-expression gene modules. The different response to two kinds of vitro models (a constant 0.2% oxygen hypoxia model and a Wayne model) were explained based on these modules. We identified potential transcription factors based on high Pearson's correlation coefficients between the modules and genes. Three modules that may be associated with hypoxic stimulation were identified, and their potential transcription factors were predicted. In the validation experiment, we determined the expression levels of genes in the modules under hypoxic condition and under overexpression of potential transcription factors (Rv0081, furA (Rv1909c), Rv0324, Rv3334, and Rv3833). The experimental results showed that the three identified modules related to hypoxia and that the overexpression of transcription factors could significantly change the expression levels of genes in the corresponding modules.

BACKGROUND Acute lung injury (ALI) is a life-threatening hypoxemic respiratory disorder with high incidence and mortality. ALI usually manifests as widespread inflammation and lung fibrosis with the accumulation of pro-inflammatory and pro-fibrotic factors and collagen. Thymic stromal lymphopoietin (TSLP) has a significant role in regulation of inflammation but little is known about its roles in lung fibrosis or ALI. This study aimed to define the role and possible regulatory mechanism of TSLP in lung fibrosis. MATERIAL AND METHODS We cultured human lung fibroblast MRC-5 cells and overexpressed or inhibited TSLP by the vector or small interfering RNA transfection. Then, the pro-fibrotic factors skeletal muscle actin alpha (α-SMA) and collagen I, and the 4 mitogen-activated protein kinases (MAPKs) - MAPK7, p38, extracellular signal-regulated kinase 1 (ERK1), and c-Jun N-terminal kinase 1 (JNK1) - were detected by Western blot. RESULTS Results showed that TSLP promoted the production of α-SMA and collagen I (P<0.001), suggesting that it can accelerate MRC-5 cell fibrosis. It also activated the expression of MAPK7, p-p38, p-ERK1, and p-JNK1, but the total MAPK7, p-38, ERK1, and JNK1 protein levels were mostly unchanged, indicating the activated MAPK pathways that might contribute to the promotion of cell fibrosis. CONCLUSIONS This study shows the pro-fibrotic role of TSLP in MRC-5 cells, suggesting TSLP is a potential therapeutic target for treating lung fibrosis in ALI. It possibly functions via activating MAPKs. These findings add to our understanding of the mechanism of fibrosis.

Dendrocalamus sinicus is the world's largest bamboo species with strong woody culms, and known for its fast-growing culms. As an economic bamboo species, it was popularized for multi-functional applications including furniture, construction, and industrial paper pulp. To comprehensively elucidate the molecular processes involved in its culm elongation, Illumina paired-end sequencing was conducted. About 65.08 million high-quality reads were produced, and assembled into 81,744 unigenes with an average length of 723 bp. A total of 64,338 (79%) unigenes were annotated for their functions, of which, 56,587 were annotated in the NCBI non-redundant protein database and 35,262 were annotated in the Swiss-Prot database. Also, 42,508 and 21,009 annotated unigenes were allocated to gene ontology (GO) categories and clusters of orthologous groups (COG), respectively. By searching against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG), 33,920 unigenes were assigned to 128 KEGG pathways. Meanwhile, 8,553 simple sequence repeats (SSRs) and 81,534 single-nucleotide polymorphism (SNPs) were identified, respectively. Additionally, 388 transcripts encoding lignin biosynthesis were detected, among which, 27 transcripts encoding Shikimate O-hydroxycinnamoyltransferase (HCT) specifically expressed in D. sinicus when compared to other bamboo species and rice. The phylogenetic relationship between D. sinicus and other plants was analyzed, suggesting functional diversity of HCT unigenes in D. sinicus. We conjectured that HCT might lead to the high lignin content and giant culm. Given that the leaves are not yet formed and culm is covered with sheaths during culm elongation, the existence of photosynthesis of bamboo culm is usually neglected. Surprisedly, 109 transcripts encoding photosynthesis were identified, including photosystem I and II, cytochrome b6/f complex, photosynthetic electron transport and F-type ATPase, and 24 transcripts were characterized as antenna proteins that regarded as the main tool for capturing light of plants, implying stem photosynthesis plays a key role during culm elongation due to the unavailability of its leaf. By real-time quantitative PCR, the expression level of 6 unigenes was detected. The results showed the expression level of all genes accorded with the transcriptome data, which confirm the reliability of the transcriptome data. As we know, this is the first study underline the D. sinicus transcriptome, which will deepen the understanding of the molecular mechanisms of culm development. The results may help variety improvement and resource utilization of bamboos.

Immunization with pertussis vaccine during pregnancy is recommended in a number of countries to prevent newborn deaths from whooping cough. In some jurisdictions, vaccine uptake during pregnancy is low. We undertook a survey of the knowledge, attitudes, beliefs, and behaviors of pregnant women who had been approached to participate in a randomized, controlled trial of tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy. A total of 346 women completed the survey. Knowledge about pertussis and pertussis vaccine was generally low; the mean number of correct answers was 10.65 out of 19 questions. Attitudes toward maternal immunization were generally favorable; 51.7%-94.7% of women had positive responses to 10 attitudinal statements. Substantial uncertainty was shown in responses to a number of the attitudinal statements related to vaccination during pregnancy; 22.3%-45.7% neither agreed nor disagreed with the statements. Importantly, 89% of women reported that they would get immunized with pertussis vaccine during pregnancy if their physician recommended it. We conclude that a national recommendation to be immunized with pertussis vaccine during pregnancy supported by their physicians' recommendation would be well received by Canadian women.

To examine the function of serum lactic dehydrogenase (SLDH) level after intensity-modulated radiotherapy (IMRT) as a predictive factor for and loco-regional relapse free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS), and overall survival(OS) among patients with in-situ nasopharyngeal carcinoma (NPC).

The recently emerged CRISPR/Cas9 technique has opened a new perspective on readily editing specific genes. When combined with transcription activators, it can precisely manipulate endogenous gene expression. Here, we enhanced the expression of endogenous Cdx2 and Gata6 genes by CRISPR-mediated activators, thus mouse embryonic stem cells (ESCs) were directly converted into two extraembryonic lineages, i.e., typical trophoblast stem cells (TSCs) and extraembryonic endoderm cells (XENCs), which exhibited characters of TSC or XENC derived from the blastocyst extraembryonic lineages such as cell morphology, specific gene expression, and differentiation ability in vitro and in vivo. This study demonstrates that the cell fate can be effectively manipulated by directly activating of specific endogenous gene expression with CRISPR-mediated activator.

As a multi-ethnic country, China has some indigenous population groups which vary in culture and social customs, perhaps as a result of geographic isolation and different traditions. However, upon close interactions and intermarriage, admixture of different gene pools among these ethnic groups may occur. In order to gain more insight on the genetic background of X-Chromosome from these ethnic groups, a set of X-markers (18 X-STRs and 16 X-Indels) was genotyped in 5 main ethnic groups of China (HAN, HUI, Uygur, Mongolian, Tibetan). Twenty-three private alleles were detected in HAN, Uygur, Tibetan and Mongolian. Significant differences (p < 0.0001) were all observed for the 3 parameters of heterozygosity (Ho, He and UHe) among the 5 ethnic groups. Highest values of Nei genetic distance were always observed at HUI-Uygur pairwise when analyzed with X-STRs or X-Indels separately and combined. Phylogenetic tree and PCA analyses revealed a clear pattern of population differentiation of HUI and Uygur. However, the HAN, Tibetan and Mongolian ethnic groups were closely clustered. Eighteen X-Indels exhibited in general congruent phylogenetic signal and similar cluster among the 5 ethnic groups compared with 16 X-STRs. Aforementioned results proved the genetic polymorphism and potential of the 34 X-markers in the 5 ethnic groups.

Ventricular septal defects (VSDs) constitute the most prevalent congenital heart disease (CHD), occurs either in isolation (isolated VSD) or in combination with other cardiac defects (complex VSD). Copy number variation (CNV) has been highlighted as a possible contributing factor to the etiology of many congenital diseases. However, little is known concerning the involvement of CNVs in either isolated or complex VSDs.

Stemphylium blight (SB), caused by Stemphylium botryosum, is a devastating disease in lentil production. Although it is known that accessions of Lens ervoides possess superior SB resistance at much higher frequency than the cultivated lentil species, very little is known about the molecular basis regulating SB resistance in L. ervoides. Therefore, a comprehensive molecular study of SB resistance in L. ervoides was needed to exploit this wild resource available at genebanks for use by plant breeders in resistance breeding.

Cisplatin resistance remains a major clinical obstacle to the successful treatment of non-small cell lung cancer (NSCLC). Scribble contributes to ROS-induced inflammation and cisplatin-elevated toxic reactive oxygen species (ROS) promotes cell death. However, it is unknown whether and how Scribble is involved in the cisplatin-related cell death and the underlying mechanism of Scribble in response to chemotherapies and in the process of oxidative stress in NSCLC.

Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthma. We previously identified SJMHE1, a small molecule peptide from the HSP60 protein of Schistosoma japonicum. SJMHE1 can inhibit delayed-type hypersensitivity and collagen-induced arthritis in mice. In the present study, we evaluated this peptide's potential intervention effect and mechanism on ovalbumin-induced asthma in mice. SJMHE1 treatment suppressed airway inflammation in allergic mice, decreased the infiltrating inflammatory cells in the lungs and bronchoalveolar lavage fluid, modulated the production of pro-inflammatory and anti-inflammatory cytokines in the splenocytes and lungs of allergic mice, reduced the percentage of Th2 cells and increased the proportion of Th1 and regulatory T cells (Tregs). At the same time, Foxp3 and T-bet expression increased, and GATA3 and RORγt decreased in the lungs of allergic mice. We proved that SJMHE1 can interrupt the development of asthma by diminishing airway inflammation in mice. The down-regulation of Th2 response and the up-regulation of Th1 and Tregs response may contribute to the protection induced by SJMHE1 in allergic mice. SJMHE1 can serve as a novel therapy for asthma and other allergic or inflammatory diseases.

To determine whether E.N.T inpatients have a higher prevalence of mental illness than the general population and whether certain diseases are more likely to be associated with mental illness than other diseases.

Highly pure 1T MoS2 nanosheets were grown at 200 °C by a hydrothermal process. The effects of mild annealing on the structural and physical properties of the MoS2 were studied by heating the nanosheets in air and vacuum up to 350 °C. It was found that the annealing leads to an increase in resistivity for the nanosheets by 3 orders of magnitude, the appearance of two absorption bands in the visible range, and a hydrophilic to hydrophobic change in the surface wetting properties. Monitoring of the annealing process by Raman spectroscopy indicates that the material property changes are associated with a 1T to 2H MoS2 phase transition, with activation energies of 517 meV in air and 260 meV in vacuum. This study provides another way to control the electrical, optical, and surface properties of MoS2 nanosheets for fulfilling the needs of various applications.

A wheat protein phosphatase PP2C-a10, which interacted with TaDOG1L1 and TaDOG1L4, promoted seed germination and decreased drought tolerance of transgenic Arabidopsis. Seed dormancy and germination are critical to plant fitness. DELAY OF GERMINATION 1 (DOG1) is a quantitative trait locus for dormancy in Arabidopsis thaliana. Some interactions between DOG1 and the type 2C protein phosphatases (PP2Cs) have been reported in Arabidopsis. However, the research on molecular functions and regulations of DOG1Ls and group A PP2Cs in wheat (Triticum aestivum. L), an important crop plant, is rare. In this study, the whole TaDOG1L family was identified. Expression analysis revealed that TaDOG1L2, TaDOG1L4 and TaDOG1L-N2 specially expressed in wheat grains, while others displayed distinct expression patterns. Yeast two-hybrid analysis of TaDOG1Ls and group A TaPP2Cs revealed interaction patterns differed from those in Arabidopsis, and TaDOG1L1 and TaDOG1L4 interacted with TaPP2C-a10. The qRT-PCR analysis showed that TaPP2C-a10 exhibited the highest transcript level in wheat grains. Further investigation showed that ectopic expression of TaPP2C-a10 in Arabidopsis promoted seed germination and decreased sensitivity to ABA during germination stage. Additionally, TaPP2C-a10 transgenic Arabidopsis exhibited decreased tolerance to drought stress. Finally, the phylogenetic analysis indicated that TaPP2C-a10 gene was conserved in angiosperm during evolutionary process. Overall, our results reveal the role of TaPP2C-a10 in seed germination and abiotic stress response, as well as the functional diversity of TaDOG1L family.

Chromoplasts are colored plastids that synthesize and store massive amounts of carotenoids. Chromoplast number and size define the sink strength for carotenoid accumulation in plants. However, nothing is known about the mechanisms controlling chromoplast number. Previously, a natural allele of Orange (OR), ORHis, was found to promote carotenoid accumulation by activating chromoplast differentiation and increasing carotenoid biosynthesis, but cells in orange tissues in melon fruit and cauliflower OR mutant have only one or two enlarged chromoplasts. In this study, we investigated an ORHis variant of Arabidopsis OR, genetically mimicking the melon ORHis allele, and found that it also constrains chromoplast number in Arabidopsis calli. Both in vitro and in vivo experiments demonstrate that ORHis specifically interacts with the Membrane Occupation and Recognition Nexus domain of ACCUMULATION AND REPLICATION OF CHLOROPLASTS 3 (ARC3), a crucial regulator of chloroplast division. We further showed that ORHis interferes with the interaction between ARC3 and PARALOG OF ARC6 (PARC6), another key regulator of chloroplast division, suggesting a role of ORHis in competing with PARC6 for binding to ARC3 to restrict chromoplast number. Overexpression or knockout of ARC3 in Arabidopsis ORHis plants significantly alters total carotenoid levels. Moreover, overexpression of the plastid division factor PLASTID DIVISION 1 greatly enhances carotenoid accumulation. These division factors likely alter carotenoid levels via their influence on chromoplast number and/or size. Taken together, our findings provide novel mechanistic insights into the machinery controlling chromoplast number and highlight a potential new strategy for enhancing carotenoid accumulation and nutritional value in food crops.

Equalizing basic public health services (BPHS) for all has been one goal of the health system reform in China since 2009. At the end of the 12th five-year plan, we conducted a series of surveys to understand BPHS implementation in Southwest China, and firstly reported implementation of health education (HE) and explore the barriers to HE delivery.

Nitrogen (N), phosphorus (P), potassium (K), and water are four crucial factors that have significant effects on strawberry yield and fruit quality. We used a 11 that involved 36 treatments with five levels of each of the four variables (N, P, and K fertilizers and water) to optimize fertilization and water combination for high yield and quality. Moreover, we used the SSC/TA ratio (the ratio of soluble solid content to titratable acid) as index of quality. Results showed that N fertilizer was the most important factor, followed by water and P fertilizer, and the N fertilizer had significant effect on yield and SSC/TA ratio. By contrast, the K fertilizer had significant effect only on yield. N×K fertilizer interacted significantly on yield, whereas the other interactions among the four factors had no significant effects on yield or SSC/TA ratio. The effects of the four factors on yield and SSC/TA ratio were ranked as N fertilizer > water > K fertilizer > P fertilizer and N fertilizer > P fertilizer > water > K fertilizer, respectively. The yield and SSC/TA ratio increased when NPK fertilizer and water increased, but then decreased when excessive NPK fertilizer and water were applied. The optimal fertilizer and water combination were 22.28-24.61 g plant-1 Ca (NO3)2·4H2O, 1.75-2.03 g plant-1 NaH2PO4, 12.41-13.91 g plant-1 K2SO4, and 12.00-13.05 L water plant-1 for yields of more than 110 g plant-1 and optimal SSC/TA ratio of 8.5-14.

Recently, RNA interfering (RNAi) has become a promising approach for cancer therapy. However, the application of RNAi for clinics is still hindered due to the lack of safe and efficient carriers. In this study, a pH-responsive micelle based on polycaprolactone-block-poly 2-(dimethylamino)ethyl methacrylate (PCL-PDEM) cationic copolymer was developed to carry short interfering RNA (siRNA) for silencing interleukin 8 (IL-8) gene in hepatoma cancer cells. The transfection efficiency of the PCL-PDEM-siRNA/quantum dots (QDs) nanoplex has reached about 70%, and the expression level of IL-8 decreased about 63%. Furthermore, the codelivery of QDs and siRNA has been realized, which is beneficial to visualize the process of siRNA delivery. No considerable cytotoxicity from the nanoparticles has been observed, indicating that our responsive cationic micelle is potential in clinical trial for hepatoma cancer therapy.