Improved Patient Adherence to Family-Based Helicobacter pylori Infection Control and Management Strategy in Central China and Its Influencing Factors.

BACKGROUND: Patient adherence status to the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management strategy remains unclear, so are its influencing factors. We aim to investigate family members' adherence and its influencing factors during the family-based H. pylori infection management practice for related disease prevention. MATERIALS AND METHODS: Based on our previously family-based H. pylori survey in 2021, 282 families including 772 individuals were followed up 2 years after the initial survey to compare if the investigation and education might improve family member's adherence. The participant's adherence to H. pylori infection awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were followed up, and their influencing factors were also analyzed. RESULTS: The overall participant's adherence to recommendations on H. pylori awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were 77% (187/243), 67.3% (138/205), 60.1% (211/351), 46.5% (107/230), 45.6% (159/349), and 39.1% (213/545), respectively; and all showed improvements compared with their prior survey stages. The top reasons for rejection to treatment, retest, and gastroscopy were forgetting or unaware of H. pylori infection (30.3%), busy (32.8%), and asymptomatic (67.9%), respectively. Independent risk factor for low adherence to treatment was occupation (e.g., staff: OR 4.49, 95% CI 1.34-15.10). Independent favorable factors for treatment adherence were individuals at the ages of 18-44 years (OR 0.19, 95% CI 0.04-0.89) and had a large family size (e.g., four family members: OR 0.15, 95% CI 0.06-0.41); for retest adherence, it was individuals at the ages of 60-69 years (OR 0.23, 95% CI 0.06-0.97); for gastroscopy adherence, it was individuals at the age of 60-69 years (OR 0.46, 95% CI 0.28-0.75), and with gastrointestinal symptoms (OR 0.57, 95% CI 0.36-0.90). CONCLUSIONS: Family-based H. pylori management increases individual adherence to treatment, retest, and awareness, and there are also improved adherence to gastroscopy, publicity, and personal hygiene recommendations; further efforts are required to enhance the individual adherence rate for related disease prevention.

Genomic prediction and genome-wide association studies for additive and dominance effects for body composition traits using 50 K and imputed high-density SNP genotypes in Yunong-black pigs.

Body composition traits are complex traits controlled by minor genes and, in hybrid populations, are impacted by additive and nonadditive effects. We aimed to identify candidate genes and increase the accuracy of genomic prediction of body composition traits in crossbred pigs by including dominance genetic effects. Genomic selection (GS) and genome-wide association studies were performed on seven body composition traits in 807 Yunong-black pigs using additive genomic models (AM) and additive-dominance genomic models (ADM) with an imputed high-density single nucleotide polymorphism (SNP) array and the Illumina Porcine SNP50 BeadChip. The results revealed that the additive heritabilities estimated for AM and ADM using the 50 K SNP data ranged from 0.20 to 0.34 and 0.11 to 0.30, respectively. However, the ranges of additive heritability for AM and ADM in the imputed data ranged from 0.20 to 0.36 and 0.12 to 0.30, respectively. The dominance variance accounted for 23% and 27% of the total variance for the 50 K and imputed data, respectively. The accuracy of genomic prediction improved by 5% on average for 50 K and imputed data when dominance effect were considered. Without the dominance effect, the accuracies for 50 K and imputed data were 0.35 and 0.38, respectively, and 0.41 and 0.43, respectively, upon considering it. A total of 12 significant SNP and 16 genomic regions were identified in the AM, and 14 significant SNP and 21 genomic regions were identified in the ADM for both the 50 K and imputed data. There were five overlapping SNP in the 50 K and imputed data. In the AM, a significant SNP (CNC10041568) was found in both body length and backfat thickness traits, which was in the PLAG1 gene strongly and significantly associated with body length and backfat thickness in pigs. Moreover, a significant SNP (CNC10031356) with a heterozygous dominant genotype was present in the ADM. Furthermore, several functionally related genes were associated with body composition traits, including MOS, RPS20, LYN, TGS1, TMEM68, XKR4, SEMA4D and ARNT2. These findings provide insights into molecular markers and GS breeding for the Yunong-black pigs.

Trophectoderm biopsy is associated with adverse obstetric outcomes rather than neonatal outcomes.

BACKGROUND: With the wide application of preimplantation genetic testing (PGT) with trophectoderm (TE) biopsy, the safety of PGT has always been a concern. Since TE subsequently forms the placenta, it is speculated that the removal of these cells was associated with adverse obstetrical or neonatal outcomes after single frozen-thawed blastocyst transfer (FBT). Previous studies report contradictory findings with respect to TE biopsy and obstetric and neonatal outcomes. METHODS: We conducted a retrospective cohort study including 720 patients with singleton pregnancies from single FBT cycles who delivered at the same university-affiliated hospital between January 2019 and March 2022. The cohorts were divided into two groups: the PGT group (blastocysts with TE biopsy, n = 223) and the control group (blastocysts without biopsy, n = 497). The PGT group was matched with the control group by propensity score matching (PSM) analysis at a ratio of 1:2. The enrolled sample sizes in the two groups were 215 and 385, respectively. RESULTS: Patient demographic characteristics were comparable between the groups after PSM except for the proportion of recurrent pregnancy loss, which was significantly higher in the PGT cohort (31.2 vs. 4.2%, P < 0.001). Patients in the PGT group had significantly higher rates of gestational hypertension (6.0 vs. 2.6%, adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.18-7.18, P = 0.020) and abnormal umbilical cord (13.0 vs. 7.8%, aOR 1.94, 95% CI 1.08-3.48, P = 0.026). However, the occurrence of premature rupture of membranes (PROM) (12.1 vs. 19.7%, aOR 0.59, 95% CI 0.35-0.99, P = 0.047) was significantly lower in biopsied blastocysts than in unbiopsied embryos. There were no significant differences in regard to other obstetric and neonatal outcomes between the two groups. CONCLUSIONS: Trophectoderm biopsy is a safe approach, as the neonatal outcomes from biopsied and unbiopsied embryos were comparable. Furthermore, PGT is associated with higher risks of gestational hypertension and abnormal umbilical cord but may have a protective effect on PROM.

Lymphoid enhancer binding factor 1 is associated with nose color in Yunong black pigs.

Yunong black pig is an indigenous black pig breed being cultivated that has a pure black whole body. However, some individuals appear with a white spot on the nose. We performed case-control association studies and FST approaches in 76 animals with nose color records (26 white-nosed pigs vs. 50 black-nosed pigs) by Illumina Porcine SNP50 BeadChip data. In total, 76 SNPs, which included 2 genome-wide significant SNPs and 18 chromosome-wide suggestive SNPs, were identified by association study. The top-ranked 0.1% windows of FST results as signals under selection and 24 windows were selected. The lymphoid enhancer binding factor 1 was identified as candidate gene with strong signal in analyses of genome-wide association study and FST in black- and white-nosed pigs. Overall, our findings provide evidence that nose color is a heritable trait influenced by many loci. The results contribute to expand our understanding of pigmentation in pigs and provide SNP markers for skin color and related traits selection in Yunong black pigs. Additional research on the genetic link between nose pigmentation is needed.

Genome-wide association study reveals the candidate genes for reproduction traits in Yunong black pigs.

Enhancing pig reproductive efficiency has the potential to have a significant positive economic impact on the pig business. We collected four reproduction records of 734 Yunong black pigs in this study, including the total number of piglets born (TNB), the number born alive (NBA), the average birth interval of piglets (ABI) and the average birth weight (ABW). A total of 453 Yunong black pigs were genotyped with Porcine 50K SNP BeadChip. Twenty-five SNPs and 35 genomic areas were found to have a substantial impact on the reproductive performance of Yunong black pigs by single-locus GWAS and single-step GWAS (ssGWAS). For the ssGWAS, we found that the two genomic regions (12.67-13.85 and 14.26-15.01 Mb) on Sus scrofa chromosome X were associated with TNB, NBA and ABI. It is worth noting that CNC10110530 and CNC100141254 significantly affected the TNB by both GWAS methods. Finally, we further determined the gene functions by enrichment analysis and a literature search, and identified 28 of them as candidate genes affecting the reproductive performance of Yunong black pigs, including RET, EIF1AX, NELL2, CTPS2, S100G, RBBP7 and PDHA1. This study further promotes understanding of the genetic mechanism of porcine reproductive performance, and also provides more molecular markers for pig breeding.

Integrated testis transcriptome and whole genome analysis of sexual maturity in Large White and Tongcheng pigs.

Testicular development and spermatogenesis play critical roles in male fertility and sexual maturation. To explore the genetic basis and key genes related to sexual maturity, we measured serum testosterone content and analysed testis tissue sections of Large White (LW) and Tongcheng (TC) boars at an immature age. We then screened differentially expressed genes (DEGs) in testis development in both breeds using RNA-seq. Finally, we analysed the selection signatures of both breeds to investigate which DEGs were subjected to positive selection. Our findings showed that serum testosterone contents in TC pigs (~4 ng/mL) were much higher than those in LW pigs (<0.95 ng/mL). Haematoxylin and eosin staining of testicular sections showed that the cross-sectional areas and perimeters of the seminiferous tubules in TC testes were larger and longer than those in LW pigs. A total of 5068 DEGs were selected by filtering criteria of q value <0.05 and |log2 (fold change)| ≥ 1. Gene Ontology analysis revealed that 250 genes were enriched in 11 biological process categories involved in sexual maturity. Most candidate genes, including TRIP13, NR6A1, STRA8, PCSK4, ACRBP, TSSK1B and TSSK6, were under positive selection. These results provide a better understanding of the genetic basis for testicular maturation and are useful for enhancing boar reproductive traits through molecular breeding.

An association study on imputed whole-genome resequencing from high-throughput sequencing data for body traits in crossbred pigs.

Body traits are important economic factors in the pig industry. Genome-wide association studies (GWASs) have been widely applied using high-density genotype data to detect QTL in pigs. The aim of the present study was to detect the genetic variants significantly associated with body traits in crossbred pigs using the Illumina Porcine SNP50 BeadChip and imputed whole-genome sequence data. A set of seven body traits - body length, body height, chest circumference, cannon bone circumference, leg buttock circumference, back fat thickness and loin muscle depth - were measured. Moderate to high heritabilities were obtained for most traits (from 0.14 to 0.46), and significant genetic and phenotypic correlations among them were observed. GWAS identified 714 significantly associated SNPs located at 39 regions on all autosomes for body traits, and a total of seven functionally related candidate genes: PIK3CD, HOXA, PCGF2, CHST11, COL2A1, BMI1 and OSR2. Functional enrichment analysis revealed that candidate genes were enriched in the estrogen signaling pathway, embryonic skeletal system morphogenesis and embryonic skeletal system development. These results aim to uncover the genetic mechanisms underlying body development and marker-assisted selection programs focusing on body traits in pigs.

Awareness for Endoscopic Screening Among Accompanying Children of Hospitalized Esophageal Cancer Patients in Henan.

The free generalized endoscopic screening for diagnosis of early esophageal cancer and precancerous lesion could not be satisfactorily implemented in China. At present, the decision to accept endoscopic screening at their own expense may largely depend on the public awareness. This study was aimed to investigate the awareness and other influencing factors associated with the accompanying children of esophageal cancer patients after their hospitalization. In this cross-sectional study, from April to June 2016, 233 children of accompanying patients, who were admitted within the last 1 year due to esophageal cancer in three affiliated hospitals of Zhengzhou University and Anyang Tumor Hospital, were enrolled. In addition, telephone surveys were conducted to investigate their awareness about endoscopic screening. One child was corresponded to an esophageal cancer patient. About half (47.6%, 111/233) of the children were unaware that endoscopic screening could detect early esophageal cancer and precancerous lesion. There was no significant difference in their awareness rates between hospitals with different administration levels. Besides, the males who had a lower family income and lower education level showed a poor awareness rate (P < 0.05). The overall awareness rate among the accompanying children of patients on endoscopic screening was rather low in Henan province (China). Hence, the health education and awareness on the importance of endoscopic screening for early detection of esophageal cancer should be promoted among children accompanying the patients. More attention should be focused towards the subject group, particularly among those male children with lower educational level and family income.

Effect of heavy metals pollution on the composition and diversity of the intestinal microbial community of a pygmy grasshopper (Eucriotettix oculatus).

Heavy metal pollution in the environment is mostly manifested as a multi-elemental compound pollution. The effect of the long-term exposure to heavy metal pollution on the gut microbes of insects has remained unknown. For the current work, the population of Eucriotettix oculatus living in mining areas around the Diaojiang River with a history of hundreds of years of pollution, was selected along with the similar species living in non-mining areas to conduct a comparative study of their gut microbes. The microbial communities were analyzed using 16S rRNA amplicon sequencing. The results showed Proteobacteria to be dominant among gut microbes of E. oculatus, but the abundance of Proteobacteria was significantly increased when the insects were exposed to the environment with heavy metal pollution. The symbiotic bacteria belonging to genus Wolbachia were found to be dominant among the insect population from the non-mining area group, while the pathogenic bacteria belonging to Aeromonas were dominant among the insect population of the mining area group. The diversity analysis showed that the gut microbial community diversity of E. oculatus was reduced in the heavy metal pollution habitat. The analysis of the differences in the gut microbial population and metabolic pathways of the two groups showed that the heavy metal pollution caused the increase in pathogenic bacteria among the gut microbes of E. oculatus, which might have a negative impact on the health of the host. At the same time, probiotics and the beneficial metabolism pathways were also found to increase and enhance, helping the host to resist the damage caused by heavy metal stress. This might be one of the strategies used by E. oculatus to adapt to heavy metal pollution.

Lipidomic profiling analysis of the phospholipid molecules in SCAP-induced lipid droplet formation in bovine mammary epithelial cells.

The accumulation of lipid droplets (LDs) in the cytoplasm plays an important role in energy balance, membrane synthesis and cell signal transduction. The aim of this study was to investigate the profile of phospholipids after SCAP-induced LD formation in bovine mammary epithelial cells (BMECs). A shRNA-SCAP vector and a SCAP/SREBP vector were used to knock down and overexpress the SCAP gene in BMECs prior to evaluating the effects on LDs using Western blotting, real-time PCR, LD staining and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The average LD diameter was determined following oil red O staining. The overexpression of SCAP increased the abundance of SCD, ACACA and FASN genes and nuclear SREBP1a. In contrast, knocking down SCAP decreased the abundance of the nuclear SREBP1a protein and downregulated the abundance of target genes. Lipid droplet staining revealed that knocking down SCAP reduced LD formation and average LD diameter. In contrast, overexpression of SCAP increased the formation and size of the LDs. The results from an analysis of cellular lipids revealed that phospholipids are the predominant species in the profile of cell lipids. phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are important for determining the size of LDs. The LD formation induced by SCAP gene overexpression and knockdown underscored the role of phospholipids involved in lipid droplet formation and fusion.

Long non-coding RNA CRNDE promotes cell apoptosis by suppressing miR-495 in inflammatory bowel disease.

OBJECTIVE: This article aims to investigate the mechanism of microRNA-495 (miR-495) and long non-coding RNA CRNDE on the apoptosis of colonic epithelial cells in inflammatory bowel diseases (IBDs). METHODS: The mouse model of IBD was induced by dextran sulfate sodium (DSS), and human colonic epithelial cell lines (HT-29, LOVO, and Caco-2) were treated with DSS, and received cell transfection. RNA interference was used to down-regulate CRNDE expression. RESULTS: CRNDE and SOCS1 were highly expressed, but miR-495 was lowly expressed in the DSS-induced colitis tissues and colonic epithelial cell lines. Interference of CRNDE inhibited cell apoptosis of DSS-induced colonic epithelial cells. The interaction between CRNDE and miR-495 was confirmed by RNA immunoprecipitation and RNA pull-down assay. The target relationship between miR-495 and SOCS1 was confirmed by the luciferase reporter assay. CRNDE promoted DSS-induced colonic epithelial cell apoptosis via miR-495/SOCS1. CRNDE interference in DSS-induced colitis mouse model alleviated clinical manifestations of IBD. CONCLUSIONS: Our findings demonstrated that CRNDE promoted DSS-induced colonic epithelial cell apoptosis via suppressing miR-495 and increasing SOCS1, indicating CRNDE as a novel target of treating IBD.

hsa_circ_0006916 promotes hepatocellular carcinoma progression by activating the miR-337-3p/STAT3 axis.

BACKGROUND: Circular RNAs (circRNAs) are thought to be involved in the development of various malignancies. The expression and function of hsa_circ_0006916, a newly identified circRNA, in hepatocellular carcinoma remain unclear. METHODS: Quantitative RT-PCR was used to detect hsa_circ_0006916 in hepatocellular carcinoma. In vitro function assays were conducted to explore growth and invasion of hepatocellular carcinoma cells. Next, the mechanism of hsa_circ_0006916 function in hepatocellular carcinoma was determined by luciferase reporter and RIP assays. RESULTS: Hsa_circ_0006916 was substantially overexpressed in hepatocellular carcinoma tissues and cells. High levels of hsa_circ_0006916 in hepatocellular carcinoma patients were associated with advanced clinical characteristics. Down-regulation of hsa_circ_0006916 decreased the growth and invasion of hepatocellular carcinoma cells in vitro. The results suggested that hsa_circ_0006916 acted as a sponge of miR-337-3p and had an important functional use in the regulation of STAT3 levels in hepatocellular carcinoma cells. Moreover, miR-337-3p inhibition or STAT3 overexpression abolished the effect of hsa_circ_0006916 suppression on the progression of hepatocellular carcinoma cells. CONCLUSIONS: Our data suggest a novel hsa_circ_0006916/miR-337-3p/STAT3 axis in hepatocellular carcinoma, and provide a new target for treatment.

Generation of regulable EGFRvIII targeted chimeric antigen receptor T cells for adoptive cell therapy of glioblastoma.

Adoptive immunotherapy using chimeric antigen receptors-modified T cells (CAR-T) is a promising approach for cancer treatment. However, CARs currently applied in the clinics cannot be effectively regulated and the safety of CAR-T cell therapies remains a major concern. To improve the safety of CAR-T cells, we designed a synthetic splitting CAR (ssCAR) that can regulate T cell functions exogenously. Epidermal growth factor receptor variant III (EGFRvIII) was used as a molecular target for ssCAR. Our results indicate that both EGFRvIII and small molecule are needed for the activation of the ssCAR-T cells. AP21967 dose-dependently increased the expression of T cell activation, production of cytokines and extent of cell lysis. In conclusion, the gene switch designed in this study allows for temporal and spatial control over engineered T cells in a dose-and time-dependent manner by AP21967. Our work demonstrates the feasibility and improved safety profile of this novel treatment approach.

Novel mechanism of miRNA-365-regulated trophoblast apoptosis in recurrent miscarriage.

Clinical pregnancies increasingly end in recurrent miscarriage (RM) during the first trimester, with genetic factors shouldering the main responsibility. MicroRNAs (miRNAs) regulate gene expression in a wide array of important biological processes. We examined the potential role of dysregulated miRNAs in RM pathogenesis and trophoblast development as an approach to elucidate the molecular mechanism behind RM. miRNA profiles from clinical specimens of RM and induced abortion (IA) were compared, and several miRNAs were found to be aberrantly expressed in RM samples. Among the miRNAs, miR-365 was significantly differentially expressed in RM decidual tissues. Furthermore, our results demonstrate that miR-365 functions as an upstream regulator of MDM2/p53 expression, cell cycle progression and apoptosis in trophoblasts. Bioinformatic prediction and experimental validation assays identified SGK1 as a direct target of miR-365; consistently, its protein levels were low in decidual tissues. Additionally, functional studies revealed that SGK1 silencing elicits cell cycle arrest and apoptosis in trophoblasts and that SGK1 overexpression attenuates the effects of miR-365 on apoptosis and MDM2/p53 expression. Collectively, our data provide evidence that the up-regulation of miR-365 may contribute to RM by decreasing SGK1 expression, which suggests its potential utility as a prognostic biomarker and therapeutic target for RM.

Enterovirus spectrum from the active surveillance of hand foot and mouth disease patients under the clinical trial of inactivated Enterovirus A71 vaccine in Jiangsu, China, 2012-2013.

Epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. An active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6-35 months in Jiangsu Province from 2012 to 2013. Fifty-nine infants were randomly selected from 522 non-EV-A71/CV-A16 HFMD patients. We collected 173 throat swabs and 174 rectal swabs from these infants. RT-PCR was used to amplify 5'-UTR and VP1 regions of enteroviruses and the serotypes were determined by the sequence comparison using BLAST. Twenty-one non-EV-A71/CA16 enterovirus serotypes were detected in those infants. E16, E18 were firstly reported in HFMD patients. The four top common non-EV-A71/CV-A enteroviruses among infants were CV-B3, CV-A10, CV-A6, and E9 with the HFMD incidence rates at 1.4%, 0.84%, 0.56%, and 0.47%, respectively. Over 20.8% patients were co-infected with multiple enteroviruses. Neither the course of sickness nor clinical symptoms of the co-infected patients was more severe than those infected with single enterovirus. Two patients were infected different enterovirus successively within 2 months. Several new enterovirus serotypes and multiple models of infection associated with HFMD were discovered through the active surveillance system. These data provide a better understanding of the viral etiology of HFMD.

Immunogenicity and safety of an enterovirus 71 vaccine in healthy Chinese children and infants: a randomised, double-blind, placebo-controlled phase 2 clinical trial.

BACKGROUND: Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6­36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853. FINDINGS: We randomly assigned 1200 participants, 240 (120 aged 6­11 months [infants] and 120 aged 12­36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3­954·3]), followed by those who received the 320 U formulation (497·9 [383·1­647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3­1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9­676·6] in infants and 708·4 [524·1­957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5­457·5] in infants and 498·0 [383·4­646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9­48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001). INTERPRETATION: Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials. FUNDING: The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12­5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.

Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.

Aggregation-induced emissive copper(I) complexes for living cell imaging.

Phosphorescent binuclear copper(I) complexes [Cu2(BrphenBr)2(Ph2P(CH2)nPPh2)2](ClO4)2 with different conformations are obtained by reaction of [Cu(NCCH3)4]ClO4, 3,8-dibromo-1,10-phenanthroline (BrphenBr), and corresponding diphosphine ligands, where n = 1, 4, 5, and 6 in complexes Cu-1, Cu-2, Cu-3, and Cu-4, respectively. Complex Cu-4 exhibits both the eclipsed and the staggered conformations of 18-membered Cu2C12P4 metallacycles in a 1:1 ratio in the crystal structure. All complexes are very stable to air and moisture in the solid state because of the high level of protection of all the Cu(I) centers, N and P atom centers resulting from the close contact of BrphenBr and diphosphine ligands, and what is more important is that there exist very soft P donors and the chelating effect of aromatic N atoms. The ESI-MS result through changing the collision cell energy from 0 to 20 eV suggests that the corresponding [Cu2(Ph2P(CH2)nPPh2)2](2+) cations are the thermodynamically stable species, while [Cu2(BrphenBr)2(Ph2P(CH2)nPPh2)2](ClO4)2 are stable products in crystallization kinetics in solutions. All complexes Cu-1-Cu-4 display good aggregation-induced phosphorescence emission (AIPE) behavior in CH2Cl2/hexane mixed solvents, which are suggested to arise from restriction of intramolecular rotation. Aggregation-induced emission (AIE) of complexes Cu-1-Cu-4 in PBS/DMSO (99:1, v:v) is used for living HeLa cell imaging successfully with green intracellular emission image.

Epithelial-mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells.

Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelial-mesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhancement the binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention.

Metal-free [3 + 2 + 1]/[2 + 2 + 1] biscyclization: stereospecific construction with concomitant functionalization of indolizin-5(1H)-one.

A metal-free [3 + 2 + 1]/[2 + 2 + 1] biscyclization strategy has been developed for the stereospecific construction with concomitant derivation of biologically significant indolizin-5(1H)-ones from simple and commercial starting materials. The transformations are notable because they can yield five new σ bonds and six stereocenters including a quaternary carbon center in a single operation.