Four centrosome-related genes to predict the prognosis and drug sensitivity of patients with colon cancer.

BACKGROUND: As the primary microtubule organizing center in animal cells, centrosome abnormalities are involved in human colon cancer. AIM: To explore the role of centrosome-related genes (CRGs) in colon cancer. METHODS: CRGs were collected from public databases. Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort. Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature (CRS) to score colon cancer patients. A nomogram was developed to evaluate the CRS risk in colon cancer patients. An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy, chemotherapy, and targeted therapy. Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes. RESULTS: A total of 726 CRGs were collected from public databases. A CRS was constructed, which consisted of the following four genes: TSC1, AXIN2, COPS7A, and MTUS1. Colon cancer patients with a high-risk signature had poor survival. Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+ T cells. Regarding treatment response, patients with a high-risk signature were resistant to immunotherapy, chemotherapy, and targeted therapy. COPS7A expression was relatively high in endothelial cells and fibroblasts. MTUS1 expression was high in endothelial cells, fibroblasts, and malignant cells. CONCLUSION: We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients, contributing to the development of individualized treatment for colon cancer.

[Ecological Risk and Migration Patterns of Heavy Metals in Soil and Crops in the Lead-Zinc Mining Area in Guizhou, China].

An accumulation of heavy metals in soil poses a risk to the ecological environment and human health. In this study, the concentrations of heavy metals in soil and crops were examined in a lead-zinc mining area in Guizhou Province, China. The distribution and sources of heavy metals were analyzed using GIS spatial mapping. The potential ecological risks of heavy metals were assessed using the potential ecological risk index (RI), and the human health risk assessment method recommended by the United States Environmental Protection Agency (USEPA) was used to quantify the health risk of residents exposed to heavy metals in the soil around lead-zinc mines. According to the results, the average of concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the soil were 58, 7.9, 175, 64, 0.461, 65, 1539, and 2513 mg·kg-1, respectively, which were significantly higher than the background values in Guizhou Province. It was found that the As, Cd, Cu, Hg, Pb, and Zn concentrations were extremely irregular in the soil and that the concentrations decreased significantly with the distance to the smelters, which were greatly disturbed by human activities. Comprehensive evaluation of soil heavy metals using the potential ecological risk index revealed that the risks of soil heavy metals were pole-strength and strong levels, and Cd constituted the primary ecological risk factor. A total of 22% and 10% of the corn samples contained Pb and As above the heavy metal pollution thresholds in the national food safety standards. According to human health risk assessments, heavy metals in the soil present potential non-carcinogenic risks to adults or children, and pose a potential carcinogenic risk to children. Soil pH was an important controlling factor affecting the bioavailability, migration, and accumulation of Cd in soil-crop systems. This study provides data and theoretical support for the prevention and control of soil pollution in lead-zine mining areas.

[Selenium Threshold for the Delimitation of Natural Selenium-Enriched Land].

The nationwide Se-enriched threshold plays a key role in identifying China's selenium-enriched land resources and developing characteristic agricultural practices. In this study, we used the cooperative data of 10222 sets of crops and roots in China for the past 10 years with a systematic analysis of the selenium content characteristics of the soil and the status of selenium-enriched agricultural products. The preliminary estimates of the selenium-enriched threshold based on a bulk crop-soil linear model and population selenium-intake are presented. Finally, a collaborative analysis model of soil selenium-enrichment rate and crop selenium-enrichment rate is established, coming up with the nationwide Se-enriched threshold:total selenium ≥ 0.40 µg·g-1 in paddy soil, and total selenium ≥ 0.30 µg·g-1 in dryland soil. The threshold passed the feasibility test in 13 provinces, providing strong support for the China Geological Survey to formulate and promulgate this technical standard for the delimitation of the natural selenium-enriched land.

[Ecological Risk Assessment of Heavy Metals at Township Scale in the High Background of Heavy Metals, Southwestern, China].

Heavy metals (HMs) are naturally occurring elements that have high natural background levels in the environment. Therefore, it is important to conduct ecological risk assessment and identify potential sources of HMs. In the past, studies were conducted at the regional scale. The accuracy of those studies could not meet the needs of spatial planning and natural resource management. Therefore, it is necessary to conduct ecological risk assessment at the township scale. In this study, 1092 soil samples (from 0-20 cm depth) were collected in the town of Reshui, an area with high background levels of soil HMs with the parent material of carbonatite, which is commonly found in Southwest China. The town of Reshui is a multi-ecological risk superimposed area where the ecological risk is high. In this study, concentrations of HMs (Cd, Cr, As, Hg, Pb, Cu, Zn, and Ni) in the topsoil were analyzed, and statistical analysis (SA), geographic information system (GIS) modeling, and positive matrix factorization (PMF) analysis were performed. The geoaccumulation index (Igeo) and potential ecological risk index (PERI) were applied for the ecological risk assessment and quantification of the sources of the soil HMs. The mean values of HM concentrations in the topsoil were 18.1, 1.18, 174.1, 202.2, 0.09, 71.1, 34.9, and 167.2 mg ·kg-1for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, respectively, which were considerably higher than the average background value (ABV) in soils in Yunnan Province except for As and Pb. The average concentrations of Cd, Cr, Cu, and Ni exceeded the screening values specified in the soil contamination risk in agricultural land (GB 15618-2018) by 5.82, 1.16, 4.04, and 1.02 times, respectively. The Igeo value shows that the major pollutant is Cu in the surface soil of the study area, followed by Cr, and Cd. Speciation analysis of HMs indicates that HMs (Cr, As, Pb, Cu, Zn, and Ni) mainly exist in the residual form, mostly from the geological background with low bioavailability. The potential effective components of Hg have higher levels, but the total amount of Hg and its pollution risk are lower. Cd has a high bioavailability ratio, is easy to enter the soil solution and be absorbed by crops, and is the HM with the highest pollution risk in the study area. The PERI shows that the proportions of low ecological risk, moderate risk, and high risk soil samples are 44.23%, 54.40%, and 1.37% of the total number of samples, respectively. Hg and Cd were the major sources of risk because of their high toxicity coefficient. The PMF analysis indicates that there are four major sources of HMs in the study area: human activity, natural sources, coal mining and traffic emissions, and agricultural sources with the risk contribution ratios of 9.29%, 53.67%, 11.23%, and 25.81%, respectively. The PMF analysis effectively quantified the ecological risk from these sources, providing a reference for further pollution control and prevention measures.

Synthesis, biological evaluation of benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety as potential anti-oxidant and anti-inflammatory agents.

Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC50 values in ABTS+ bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition.

Correlation of serum vitamin D, adipose tissue vitamin D receptor, and peroxisome proliferator-activated receptor γ in women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Obesity and overweight are closely related to metabolic diseases and diabetes. However, the role of adipose tissue in the pathogenesis of GDM remains to be studied. The aim of this study was to investigate the correlation of vitamin D (VD) levels, VD receptor (VDR), and peroxisome proliferator-activated receptor γ (PPARγ) expression with GDM in overweight or obese women. METHODS: One hundred and forty pregnant women with full-term single-birth cesarean-section were selected as the study subjects and grouped (70 GDM women, including 35 non-overweight/non-obese women [group G1] and 35 women with overweight or obesity [group G2]; 70 pregnant women with normal glucose tolerance, including 35 non-overweight/non-obese women [group N1] and 35 overweight/obese women [group N2]). The levels of serum VD, blood biochemistry, and adiponectin were compared in these women. Subcutaneous adipose tissue was isolated from the abdominal wall incision. VDR and PPARγ messenger RNA (mRNA) transcript levels in these adipose tissues were quantified by real-time polymerase chain reaction. The differences between the levels of PPARγ protein and phosphorylated PPARγ Ser273 were detected by Western blotting. RESULTS: The serum VD level of GDM women was lower in comparison to that of women with normal glucose tolerance (G1 vs. N1: 20.62 ±â€Š7.87 ng/mL vs. 25.85 ±â€Š7.29 ng/mL, G2 vs. N2: 17.06 ±â€Š6.74 ng/mL vs. 21.62 ±â€Š7.18 ng/mL, P < 0.05), and the lowest in overweight/obese GDM women. VDR and PPARγ mRNA expression was higher in the adipose tissues of GDM women in comparison to that of women with normal glucose tolerance (VDR mRNA: G1 vs. N1: 210.00 [90.58-311.46] vs. 89.34 [63.74-159.92], G2 vs. N2: 298.67 [170.84-451.25] vs. 198.28 [119.46-261.23], PPARγ mRNA: G1 vs. N1: 100.72 [88.61-123.87] vs. 87.52 [66.37-100.04], G2 vs. N2: 117.33 [100.08-149.00] vs. 89.90 [76.95-109.09], P < 0.05), and their expression was the highest in GDM + overweight/obese women. VDR mRNA levels positively correlated with the pre-pregnancy body mass index (BMI), pre-delivery BMI, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and PPARγ mRNA while it negatively correlated with the VD and the adiponectin levels (r = 0.395, 0.336, 0.240, 0.190, 0.235, -0.350, -0.294, respectively, P < 0.05). The degree of PPARγ Ser273 phosphorylation increased in obese and GDM pregnant women. PPARγ mRNA levels positively correlated with pre-pregnancy BMI, pre-delivery BMI, FBG, HOMA-IR, serum total cholesterol, triglyceride, free fatty acid, and VDR mRNA, while it negatively correlated with the VD and adiponectin levels (r = 0.276, 0.199, 0.210, 0.230, 0.182, 0.214, 0.270, 0.235, -0.232, -0.199, respectively, P < 0.05). CONCLUSIONS: Both GDM and overweight/obese women had decreased serum VD levels and up-regulated VDR and PPARγ mRNA expression in adipose tissue, which was further higher in the overweight or obese women with GDM. VD may regulate the formation and differentiation of adipocytes through the VDR and PPARγ pathways and participate in the occurrence of GDM.

A novel small-molecule PI3K/Akt signaling inhibitor, W934, exhibits potent antitumor efficacy in A549 non-small-cell lung cancer.

Small-molecule targeted antitumor drugs are considered to be a promising treatment that can improve the efficacy and reduce side effects. PI3K/Akt signaling pathway is constantly activated in various cancers. We recently synthesized a series of novel compounds of PI3K/Akt pathway inhibitors and found the most effective analog to be W934. In this study, we explored the in-vitro and in-vivo antitumor effects of W934 on A549 non-small-cell lung cancer cells and HCT116 colorectal cancer cells. In-vitro assays showed that W934 caused an inhibition of PI3Kα kinase. W934 can significantly suppress the viability of A549 and HCT116 cells with IC50 values of 0.25 and 0.23 µmol/l, respectively. Besides, the inhibitory effects on cell migration, invasion and apoptosis were also observed after treatment of W934 for the indicated hours. According to the cell cycle analysis, W934 caused an inhibition of G0-G1 phase progression and correspondingly decreased the percentage of cells in S and G2-M phases. Results of western blotting indicated that W934 concentration dependently suppressed the activation of the PI3K/Akt pathway. Meanwhile, the in-vivo effect was studied in an A549 xenograft mouse model. Oral administration of W934 inhibited the tumor growth in a dose-dependent manner. Hereby, W934 might be considered as a potential therapeutic drug candidate for non-small-cell lung cancer treatment.

Discovery of 2-(aminopyrimidin-5-yl)-4-(morpholin-4-yl)-6- substituted triazine as PI3K and BRAF dual inhibitor.

AIM: The discovery and development of novel agents simultaneously targeting PI3K/AKT/mammalian target of rapamycin and Ras/RAF/MEK, two signaling pathways, are urgent to improve the curative effect of kinase inhibitors and overcome acquired resistance. METHODS/RESULTS: In the present study, 2-(2-aminopyrimidin-5-yl)-4-(morpholin-4-yl)-6-(N-cyclopropyl-N- (1-benzoylpiperidin-4-yl))triazines/pyrimidines were designed as PI3K and BRAF dual inhibitors. The synthesized 20 compounds exhibited potent antiproliferative effects in vitro against HCT116, A375, MCF-7, Colo205, A549 and LOVO cancer cell lines. The tested compounds A6, A7, A9 and A11 remarkably displayed inhibitory activities toward both PI3Kα and BRAFV600E. CONCLUSION: These results indicated that our design compounds can serve as potent PI3Kα and BRAFV600E dual inhibitors and effective antiproliferative agents, which can be further optimized to discover more potent PI3Kα and BRAFV600E dual inhibitors.

Identification of a missense mutation causing exon skipping in a neurofibromatosis type 1 patient.

Neurofibromatosis type 1 (NF1), caused by germ line mutations of the NF1 tumor-suppressor gene, is one of the most common autosomal dominant disorders. Here, we reported a NF1 patient with the mutation NF1 c.4367+1G>C. This sequence change locates at the first nucleotide of NF1 intron 32 within the consensus splice site. Compared with NF1 c.4367G>C predicted to potentially damage the wild-type donor site at c.4367, the NF1 c.4367+1G>C potentially abolishes this wild-type donor site by in silico analysis. In vitro minigene assay revealed that the NF1 c.4367+1G>C may cause exon 32 skipping. Our result provides further evidence for its clinical significance of NF1 c.4367+1G>C in clinical practise.

Increased secreted frizzled-related protein 4 and ficolin-3 levels in gestational diabetes mellitus women.

By biochemical and epidemiological similarity with type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) has some overlap between prediction markers and risk factors of T2DM. The present study aimed to establish that secreted frizzled-related protein 4 (SFRP4) and ficolin-3 levels, which have been linked to insulin resistance and the development of T2DM, are elevated in GDM women. A longitudinal prospective cohort study of 86 GDM and 273 normal glucose tolerant (NGT) pregnant women was performed. The clinical parameters, lipid profiles, and serum SFRP4 and ficolin-3 levels were tested during the early and late second-trimester and third-trimester of pregnancy. Both SFRP4 and ficolin-3 levels were significantly higher in GDM women as compared to the NGT participants at three test points (p < 0.01). Spearman's correlation analysis showed that serum SFRP4 levels were significantly positively correlated with ficolin-3 during the early and late second-trimester and third-trimester of pregnancy. The elevated SFRP4 and ficolin-3 concentrations at 16-18 weeks gestation significantly associated with GDM were conformed using binary logistic regression analysis after controlling for other variables [odds ratios (OR) with 95% confidence intervals (CI) for SFRP4: 2.84 (1.78-4.53), p < 0.01; for ficolin-3: 2.45 (1.55-3.88), p < 0.01]. In Conclusions, increased SFRP4 and ficolin-3 levels are significantly associated with GDM development and might be important risk factors for this pregnancy complication.

Discovery of 2,4,6-trisubstitued pyrido[3,4-d]pyrimidine derivatives as new EGFR-TKIs.

Targeting acquired drug resistance is the major challenge in the treatment of EGFR-driven non-small cell lung cancer (NSCLC). In this study, a novel class of compounds containing pyrido[3,4-d]pyrimidine scaffold was designed as new generation EGFR-TKIs to overcome this challenge. The most promising compound B30 inhibited HCC827 and H1975 cells growth with the IC50 values of 0.044 µM and 0.40 µM, respectively. Meanwhile, B30 displayed potent inhibitory activity against the EGFRL858R (IC50 = 1.1 nM) and EGFRL858R/T790M/C797S (IC50 = 7.2 nM). B30 could suppress EGFR phosphorylation in a dose-dependent manner in HCC827 cell line and significantly induce the apoptosis of HCC827 cells. Molecular docking indicated that the hydroxyl in B30 could form additional hydrogen bond with mutant Ser797. These findings strongly support our assumption that 2,4,6-trisubstitued pyrido[3,4-d] pyrimidine derivatives can serve as EGFR-TKIs. The predicted hydrogen bond interaction formed by a small molecule inhibitor with mutant Ser797 is available to design the fourth-generation EGFR-TKIs.

Ficolin-3/adiponectin ratio for the prediction of gestational diabetes mellitus in pregnant women.

AIMS/INTRODUCTION: To establish that the ficolin-3/adiponectin ratio is a predictor for gestational diabetes mellitus (GDM) and is eligible for screening tests for GDM. MATERIALS AND METHODS: A prospective cohort study of 86 pregnant women who developed GDM and 273 normal glucose tolerance participants was carried out. Maternal serum ficolin-3, adiponectin levels were investigated at 16-18 weeks of gestation using enzyme-linked immunosorbent assay. RESULTS: Compared with the normal glucose tolerance group, the GDM group showed significantly higher levels of ficolin-3 and the ratio of ficolin-3/adiponectin; and decreased levels of adiponectin between 16-18 weeks of gestation (P < 0.05 or P < 0.01). The cut-off values for the ratio of ficolin-3/adiponectin (≥1.06; sensitivity 90.9%, specificity 96.5%) to discriminate the pregnant women who developed GDM from the non-diabetic cases were identified using receiver operating characteristic analysis. Using binary logistic regression analysis, ficolin-3, retinol-binding protein-4 and adiponectin, but not C-reactive protein, triglyceride and free fatty acids were shown as predictive factors for GDM. CONCLUSIONS: The ratio of ficolin-3/adiponectin at 16-18 weeks of gestation was changed in pregnant women who subsequently developed GDM, and might provide effective early predicting and screening for GDM.

The physiological responses of terrestrial cyanobacterium Nostoc flagelliforme to different intensities of ultraviolet-B radiation.

Nostoc flagelliforme is a pioneer organism in the desert and exerts important ecological functions. The habitats of N. flagelliforme are characterized by intense solar radiation, while the ultraviolet B (UV-B) tolerance has not been fully explored yet. To evaluate the physiological responses of N. flagelliforme to UV-B radiation, three intensities (1 W m-2, 3 W m-2 and 5 W m-2) were used, and the changes in photosynthetic pigments, cell morphology, mycosporine-like amino acids (MAAs) synthesis and cell metabolism were comparatively investigated. Under high UV-B intensity or long term radiation, chlorophyll a, allophycocyanin and phycocyanin were greatly decreased; scanning electron microscope observations showed that cell morphology significantly changed. To reduce the damage, cells synthesized a large amount of carotenoid. Moreover, three kinds of MAAs were identified, and their concentrations varied with the changes of UV-B intensity. Under 1 W m-2 radiation, cells synthesized shinorine and porphyra-334 against UV-B, while with the increase of intensity, more shinorine turned into asterine-330. Metabolite profiling revealed the contents of some cytoprotective metabolites were greatly increased under 5 W m-2 radiation. The principal component analysis showed cells exposed to UV-B were metabolically distinct from the control sample, and the influence on metabolism was particularly dependent on intensity. The results would improve the understanding of physiological responses of N. flagelliforme to UV-B radiation and provide an important theoretical basis for applying this organism to control desertification.

Chinese Pediatric Reference Intervals for Serum Cortisol on IMMULITE 2000.

Clinical interpretation of the test results for cortisol based on continuous reference intervals with appropriate partitions improves pediatric diagnosis; however, these values are available only for Caucasians. To develop the pediatric reference intervals for Chinese population, we examined the serum cortisol levels in 1,143 healthy Chinese children aged 4-18 years (566 boys and 577 girls), using an IMMULITE 2000 Immunoassay System (Siemens Healthcare GmbH). Phlebotomy was performed at 7-9 a.m. for 284 boys and 287 girls and at 1-3 p.m. for the others. They were divided into four age groups according to the Clinical and Laboratory Standards Institute guideline EP28-A3c, with the last group further stratified according to sampling time. Separate reference intervals of 49.6-323.7, 70.9-395.3, and 90.1-448.7 nmol/L were established for children aged 4-8, 9-12, and 13-15 years, respectively. Further, reference intervals of 118.2-464.7 and 71.4-446.7 nmol/L were established for morning and afternoon cortisol levels, respectively, in children aged 16-18 years. Further studies are necessary to transfer and validate these reference intervals in other analytical systems and pediatric populations, and to allow for broader applications.

Discovery of 2-(pyridin-2-yl)aniline as a directing group for the sp2 C-H bond amination mediated by cupric acetate.

2-(Pyridin-2-yl) aniline was designed as a new, removable directing group in promoting C-H amination mediated by cupric acetate. Employing this auxiliary, the ß-C(sp2)-H bonds of benzamide derivatives can be effectively aminated with a variety of amines in moderate to good yields with good functional group tolerance in air. In addition, the quinazolinone derivatives were isolated from the reaction mixture of N-(2-(pyridin-2-yl)phenyl)benzamide with formamide or 5-nitroindole. The corresponding mechanism is discussed. These results indicate that 2-(pyridine-2-yl)aniline can serve as a directing group.

Overall evaluation of the clinical value of prenatal screening for fetal-free DNA in maternal blood.

OBJECTIVE: To explore the clinical value of prenatal screening for fetal-free DNA in maternal blood. METHODS: A total of 10,275 maternal blood samples were collected from October 2012 to May 2016 at the prenatal diagnosis center of Changzhou Woman and Children Health Hospital. RESULTS: Among 10,275 pregnant women accepted noninvasive prenatal testing (NIPT), 9 cases could not get the results after collected the blood second times. The rate of NIPT failure was 0.09%. Seventy-two cases got the NIPT positive results of trisomy 21/trisomy 18/trisomy 13, and the detection rate, specificity, positive predictive value (PPV), and false positive rate were 98.59%, 99.99%, 97.22%, and 0.02%. The top-3 indications of the study were advanced age women (34.90%), high risk (25.22%), and intermediate risk (19.56%). They all had the satisfactory results of NIPT. Fifty-seven pregnant women had the high risk of fetal sex chromosomal aneuploidies (SCA). After informed consent, 33 cases accepted prenatal diagnosis. Eighteen cases were confirmed as sex chromosome aneuploidies. The PPV was 54.54%. Compared with other SCA, the PPV of Turner syndrome was lower. One case was false negative after followed up. CONCLUSIONS: NIPT showed a broad application prospects for prenatal screening and diagnosis of fetal chromosomal diseases. We should deepen mining and analyzing the clinical data, and explore the use of NIPT more reasonably from the perspective of evidence-based medicine.

Transcriptome altered by latent human cytomegalovirus infection on THP-1 cells using RNA-seq.

Human cytomegalovirus (HCMV) has been recognized as a cause of severe, sometimes life-threatening disease in congenitally infected newborns as well as in immunocompromised individuals. However, the molecular mechanisms of the host-virus interaction remain poorly understood. Here, we profiled the expression of mRNAs and long noncoding RNAs (lncRNAs) in THP-1 cells using the emerging RNA-seq to investigate the transcriptional changes during HCMV latent infection. At 4 days post HCMV infection, a total of 169,008,624 sequence reads and 180,616 transcripts were obtained, respectively. Of these transcripts, 1,354 noncoding genes and 12,952 protein-coding genes were observed in Refseq database. Differential gene expression analysis identified 2,153 differentially expressed genes (DEGs) between HCMV-infected and mock-infected THP-1 cells, including 1,098 up-regulated genes and 1,055 down-regulated genes. These regulated genes were involved in pathways of apoptosis, inflammatory response and cell cycle progression, all of which may be implicated in viral pathogenesis. In addition, 646 lncRNAs (208 known lncRNAs and 438 novel lncRNAs) were upregulated and 424 (140 known and 284 novel) were downregulated in infected THP-1 cells. These findings have provided a dynamic scenario of DE candidate genes and lncRNAs at the virus-host interface and clearly warrant further experimental investigation associated with HCMV infection.

Vitamin D status among infants, children, and adolescents in southeastern China.

OBJECTIVE: Vitamin D deficiency and insufficiency are global public health problems, which must first be identified before they can be appropriately addressed, and yet information is strikingly lacking in most parts of the Asia and Pacific region. The study aimed to document and account for the actual situation in Wenzhou on the southeastern coast of China. SUBJECTS AND METHODS: Serum 25-hydroxyvitamin D levels among a total of 5845 infants, preschool children, school children, and adolescents aged 1-18 years were examined between March 2014 and February 2015. RESULTS: Their mean levels were (110.2±26.8), (77.5±25.7), (55.6±15.4), and (47.2±13.9) nmol/L, respectively. Older age groups were involved in increasing risk of vitamin D deficiency and insufficiency. There were significant seasonal differences in its median level and prevalence of deficiency and insufficiency among school children and adolescents, but there was no significant sex difference in mean level and prevalence in any age group. CONCLUSIONS: Vitamin D deficiency and insufficiency were prevalent among infants, preschool children, school children, and adolescents in Wenzhou. A vitamin D-rich diet and outdoor activities for 1-2 h per day under the natural conditions favorable to its endogeous synthesis do not suffice. The vitamin D status in Wenzhounese infants excelling over that in the US was the result of its supplementation thanks to the Chinese Medical Association recommendations, which should be consequently extended to more age groups. Life style shaped by socio-economic environments affects vitamin D status. Knowledge on the importance of vitamin D for healthy growth should be popularized.

Vaccination with Bivalent DNA Vaccine of α1-Giardin and CWP2 Delivered by Attenuated Salmonella typhimurium Reduces Trophozoites and Cysts in the Feces of Mice Infected with Giardia lamblia.

BACKGROUND: Giardia lamblia is one of the most common infectious protozoans in human that may cause diarrhea in travelers. Searching for antigens that induced effectively protective immunity has become a key point in the development of vaccine against giardiasis. METHODOLOGY/PRINCIPAL FINDINGS: Mice vaccinated with G. lamblia trophozozite-specific α1-giardin DNA vaccine delivered orally by attenuated Salmonella typhimurium SL7027 elicited 74.2% trophozoite reduction, but only 28% reduction in cyst shedding compared with PBS buffer control. Oral vaccination with Salmonella-delivered cyst-specific CWP2 DNA produced 89% reduction in cysts shedding in feces of vaccinated mice. Significantly, the mice vaccinated with Salmonella-delivered bivalent α1-giardin and CWP2 DNA vaccines produced significant reduction in both trophozoite (79%) and cyst (93%) in feces of vaccinated mice. This parasite reduction is associated with the strong local mucosal IgA secretion and the IgG2a-dominant systemic immune responses in vaccinated mice. CONCLUSIONS: The results demonstrate that bivalent vaccines targeting α1-giardin and CWP2 can protect mice against the colonization of Giardia trophozoite and block the transformation of cyst in host at the same time, and can be used to prevent Giardia infection and block the transmission of giardiasis.

Recognition and killing of cancer stem-like cell population in hepatocellular carcinoma cells by cytokine-induced killer cells via NKG2d-ligands recognition.

There is an urgent need for more potent and safer approaches to eradicate cancer stem cells (CSCs) for curing cancer. In this study, we investigate cancer-killing activity (CKA) of cytokine-induced killer (CIK) cells against CSCs of hepatocellular carcinoma (HCC). To visualize CSCs in vitro by fluorescence imaging, and image and quantify CSCs in tumor xenograft-bearing mice by bioluminescence imaging, HCC cells were engineered with CSC detector vector encoding GFP and luciferase controlled by Nanog promoter. We found that CIK cells have a strong CKA in vitro against putative CSCs of HCC, as shown by tumorsphere formation and time-lapse imaging. Additionally, time-lapse recording firstly revealed that putative CSCs were attacked simultaneously by many CIK cells and finally eradicated by CIK cells, indicating the necessity of achieving sufficient effector-to-target ratios. We firstly illustrated that anti-NKG2D antibody blocking partially but significantly inhibited CKA of CIK cells against putative CSCs. More importantly, intravenous infusion of CIK cells remarkably delayed tumor growth in mice with a significant decrease in putative CSC number monitored by bioluminescence imaging. Taken together, these findings demonstrate CKA of CIK cells against putative CSCs of HCC, at least in part, by NKG2D-ligands recognition.