Malignant melanoma is the deadliest form of all skin cancers. Itraconazole, a commonly used systemic antifungal drug, has been tested for its anti-tumor effects on basal cell carcinoma, prostate cance Show more
Malignant melanoma is the deadliest form of all skin cancers. Itraconazole, a commonly used systemic antifungal drug, has been tested for its anti-tumor effects on basal cell carcinoma, prostate cancer, and non-small cell lung cancer. Whether itraconazole has any specific anti-tumor effect on melanoma remains unknown. However, the goal of this study is to investigate the effect of itraconazole on melanoma and to reveal some details of its underlying mechanism. In the in vivo xenograft mouse model, we find that itraconazole can inhibit melanoma growth and extend the survival of melanoma xenograft mice, compared to non-itraconazole-treated mice. Also, itraconazole can significantly inhibit cell proliferation, as demonstrated by Ki-67 staining in itraconazole-treated tumor tissues. In in vitro, we show that itraconazole inhibits the proliferation and colony formation of both SK-MEL-28 and A375 human melanoma cells. Moreover, we demonstrate that itraconazole significantly down-regulates Gli-1, Gli-2, Wnt3A, β-catenin and cyclin D1, while it up-regulates Gli-3 and Axin-1, indicating potent inhibitory effects of itraconazole on Hedgehog (Hh) and Wnt signaling pathways. Furthermore, itraconazole significantly suppresses the PI3K/mTOR signaling pathway - indicated by the down-regulated phosphorylation of p70S6K, 4E-BP1 and AKT - but has no effect on the phosphorylation of MEK or ERK. Our data suggest that itraconazole inhibits melanoma growth through an interacting regulatory network that includes Hh, Wnt, and PI3K/mTOR signaling pathways. These results suggest that this agent has several potent anti-melanoma features and may be useful in the synergesis of other anti-cancer drugs via blockage of the Hh, Wnt and PI3K/mTOR signaling pathways. Show less
Exploring the biological functions of long non-coding RNAs (lncRNAs) has come to the foreground in recent years. Studies have indicated that the lncRNA metastasis‑associated lung adenocarcinoma transc Show more
Exploring the biological functions of long non-coding RNAs (lncRNAs) has come to the foreground in recent years. Studies have indicated that the lncRNA metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) not only regulates tumorigenesis in hepatocellular carcinoma, but also controls cell cycle progression in hematopoietic cells. The present study was designed to investigate the biological role of lncRNA MALAT1 in liver regeneration. We carried out a series of assays during liver regeneration following 2/3 partial hepatectomy in mice. We explored the functions of lncRNA MALAT1 with a series of functional analyses in vitro. We found that MALAT1 was upregulated during liver regeneration. Moreover, MALAT1 accelerated hepatocyte proliferation by stimulating cell cycle progression from the G1 to the S phase and inhibiting apoptosis in vitro. In addition, our findings also demonstrated that MALAT1 was regulated by p53 during liver regeneration, and that p53 may be a key upstream regulator of MALAT1 activity. Mechanistically, we found that MALAT1 activated the Wnt/β‑catenin pathway by inhibiting the expression of Axin1 and adenomatous polyposis coli (APC), and subsequently promoting the expression of cyclin D1. On the whole, the findings of this study suggest that MALAT1 is a critical molecule for liver regeneration. Pharmacological interventions targeting MALAT1 may thus prove to be therapeutically beneficial in liver failure or liver transplantation by promoting liver regeneration. Show less
Whole-genome and exome sequence data can be cost-effectively generated for the detection of rare-variant (RV) associations in families. Causal variants that aggregate in families usually have larger e Show more
Whole-genome and exome sequence data can be cost-effectively generated for the detection of rare-variant (RV) associations in families. Causal variants that aggregate in families usually have larger effect sizes than those found in sporadic cases, so family-based designs can be a more powerful approach than population-based designs. Moreover, some family-based designs are robust to confounding due to population admixture or substructure. We developed a RV extension of the generalized disequilibrium test (GDT) to analyze sequence data obtained from nuclear and extended families. The GDT utilizes genotype differences of all discordant relative pairs to assess associations within a family, and the RV extension combines the single-variant GDT statistic over a genomic region of interest. The RV-GDT has increased power by efficiently incorporating information beyond first-degree relatives and allows for the inclusion of covariates. Using simulated genetic data, we demonstrated that the RV-GDT method has well-controlled type I error rates, even when applied to admixed populations and populations with substructure. It is more powerful than existing family-based RV association methods, particularly for the analysis of extended pedigrees and pedigrees with missing data. We analyzed whole-genome sequence data from families affected by Alzheimer disease to illustrate the application of the RV-GDT. Given the capability of the RV-GDT to adequately control for population admixture or substructure and analyze pedigrees with missing genotype data and its superior power over other family-based methods, it is an effective tool for elucidating the involvement of RVs in the etiology of complex traits. Show less
We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mu Show more
We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent Show less
Organ-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuo Show more
Organ-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune-mediated damage may be wide spread. In this report, we describe a mitochondrial protein, branched chain α-ketoacid dehydrogenase kinase (BCKD We demonstrate that BCKD The disease induced by BCKD Show less
Yanli Liu, Su Qin, Ming Lei+5 more · 2017 · The Journal of biological chemistry · American Society for Biochemistry and Molecular Biology · added 2026-04-24
Heterochromatin protein 1 (HP1), a highly conserved non-histone chromosomal protein in eukaryotes, plays important roles in the regulation of gene transcription. Each of the three human homologs of HP Show more
Heterochromatin protein 1 (HP1), a highly conserved non-histone chromosomal protein in eukaryotes, plays important roles in the regulation of gene transcription. Each of the three human homologs of HP1 includes a chromoshadow domain (CSD). The CSD interacts with various proteins bearing the P Show less
High levels of plasma high-density lipoprotein-cholesterol (HDL-C) are inversely associated with the risk of atherosclerosis and other cardiovascular diseases; thus, pharmacological inhibition of chol Show more
High levels of plasma high-density lipoprotein-cholesterol (HDL-C) are inversely associated with the risk of atherosclerosis and other cardiovascular diseases; thus, pharmacological inhibition of cholesteryl ester transfer protein (CETP) is considered to be a therapeutic method of raising HDL-C levels. However, many CETP inhibitors have failed to achieve a clinical benefit despite raising HDL-C. In the study, we generated transgenic (Tg) rabbits that overexpressed the human CETP gene to examine the influence of CETP on the development of atherosclerosis. Both Tg rabbits and their non-Tg littermates were fed a high cholesterol diet for 16 weeks. Plasma lipids and body weight were measured every 4 weeks. Gross lesion areas of the aortic atherosclerosis along with lesional cellular components were quantitatively analyzed. Overexpression of human CETP did not significantly alter the gross atherosclerotic lesion area, but the number of macrophages in lesions was significantly increased. Overexpression of human CETP did not change the plasma levels of total cholesterol or low-density lipoprotein cholesterol but lowered plasma HDL-C and increased triglycerides. These data revealed that human CETP may play an important role in the development of atherosclerosis mainly by decreasing HDL-C levels and increasing the accumulation of macrophage-derived foam cells. Show less
Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our pr Show more
Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our previous work, compound Show less
Angioplasty and stent implantation, the most common treatment for atherosclerotic lesions, have a significant failure rate because of restenosis. This study asks whether increasing plasma high-density Show more
Angioplasty and stent implantation, the most common treatment for atherosclerotic lesions, have a significant failure rate because of restenosis. This study asks whether increasing plasma high-density lipoprotein (HDL) levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, prevents stent-induced neointimal hyperplasia. New Zealand White rabbits received normal chow or chow supplemented with 0.14% (wt/wt) des-fluoro-anacetrapib for 6 weeks. Iliac artery endothelial denudation and bare metal steel stent deployment were performed after 2 weeks of des-fluoro-anacetrapib treatment. The animals were euthanized 4 weeks poststent deployment. Relative to control, dietary supplementation with des-fluoro-anacetrapib reduced plasma cholesteryl ester transfer protein activity and increased plasma apolipoprotein A-I and HDL cholesterol levels by 53±6.3% and 120±19%, respectively. Non-HDL cholesterol levels were unaffected. Des-fluoro-anacetrapib treatment reduced the intimal area of the stented arteries by 43±5.6% ( Inhibiting cholesteryl ester transfer protein activity in New Zealand White rabbits with iliac artery balloon injury and stent deployment increases HDL levels, inhibits vascular smooth muscle cell proliferation, and reduces neointimal hyperplasia in an scavenger receptor-B1, PDZ domain-containing protein 1- and phosphatidylinositol-3-kinase/Akt-dependent manner. Show less
N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Str Show more
N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Structure-activity relationship (SAR) studies indicate that hydrophilic groups at the 2-position of the tetrazole and 3,5-bistrifluoromethyl groups on the benzene ring provide important contributions to the potency. Among these compounds, compound 17 exhibited excellent CETP inhibitory activity (IC Show less
Hyperlipidemia has unique adverse effects on pregnant women and their offspring. The underlying genetic factors related to lipid levels in pregnant populations need more studies. This study aimed to i Show more
Hyperlipidemia has unique adverse effects on pregnant women and their offspring. The underlying genetic factors related to lipid levels in pregnant populations need more studies. This study aimed to investigate the relationship between 6 single-nucleotide polymorphisms (SNPs) and plasma lipid levels during pregnancy. A total of 2060 pregnant women were recruited. Fasting plasma lipids were measured in the third trimester of pregnancy. Six SNPs (rs1260326 in GCKR, rs1800775 in CETP, rs515135 in APOB, rs1800588 in LIPC, rs964184 in ZPR1, and and rs4420638 in APOC1 of each participant were genotyped using TaqMan allelic discrimination assays. The relationships between the 6 loci and plasma lipids were analyzed using a multiple linear regression method. Two variants, rs1260326 (β = 0.220, 95% confidence interval [CI] = 0.148-0.291; P = 2.048 × 10 Loci found by genome-wide association studies to be associated with plasma lipid levels in the general population were also related to lipid levels in the third trimester of pregnancy. This finding implies that changes to lipid profiles during gestation may be associated with SNPs of lipid-related genes. Variants of lipid-related genes are important predictors for estimating lipid concentrations during the pregnancy. Show less
To explore the association between A total of 571 individuals which were randomly selected from 5692 Uyghur adults were subdivided into two groups, including 280 patients with MS and 291 control subje Show more
To explore the association between A total of 571 individuals which were randomly selected from 5692 Uyghur adults were subdivided into two groups, including 280 patients with MS and 291 control subjects, using the group-matching method after matching for gender. We detected (1) Significant differences were found involving the frequency distribution of genotypes and alleles of rs1800775, rs3764261, rs12149545, rs711752, and rs708272 between the control and MS groups (all Show less
Extensive studies have demonstrated that biochanin A (BCA) has a significant hypolipidemic effect. However, its mechanism of action is not clear. In this context, the effect of BCA on a high-fat diet Show more
Extensive studies have demonstrated that biochanin A (BCA) has a significant hypolipidemic effect. However, its mechanism of action is not clear. In this context, the effect of BCA on a high-fat diet (HFD)-induced hyperlipidemia in mice was determined. The results showed that treatment with a medium dose of biochanin A (BM) significantly decreased low-density lipoprotein cholesterol (LDL-C) 85% (from 1.196 ± 0.183 to 0.181 ± 0.0778 mM) and total cholesterol (TC) 39% (from 5.983 ± 0.128 to 3.649 ± 0.374 mM) levels, increased lipoprotein lipase (LPL) 96% (from 1.421 ± 0.0982 to 2.784 ± 0.177 U/mg protein) and hepatic triglyceride lipase (HTGL) 78% (from 1.614 ± 0.0848 to 2.870 ± 0.0977 U/mg protein) activities, significantly improved fecal lipid levels, and lowered the epididymal fat index in hyperlipidemic mice compared with the HFD control mice (p < 0.05). In vitro, the high antioxidant capacity of BCA was determined by the FRAP assay, ABTS Show less
This study aimed to explore the associations of the cholesteryl ester transfer protein (CETP) gene TaqIB and D442G polymorphisms with essential hypertension (EH). In this case-control study, 883 hyp Show more
This study aimed to explore the associations of the cholesteryl ester transfer protein (CETP) gene TaqIB and D442G polymorphisms with essential hypertension (EH). In this case-control study, 883 hypertensive patients and 1044 normal controls were randomly selected from the Mongolian population of China. Polymerase chain reaction (PCR) and direct sequencing of PCR products were used to identify the genotypes. Haplotype analysis was performed by estimating the haplotype frequencies using the online SHEsis package. The distribution frequency of the B2-G haplotype was significantly lower in the EH group than in the control group (0.7% vs. 1.9%, P = 0.001, OR = 0.359 [0.188-0.689]). Subjects with the B2B2 genotype showed significantly lower levels of total cholesterol (TC) (P < 0.05). When subgrouped by sex, male subjects with the B2B2 genotype showed significantly increased high-density lipoprotein cholesterol and decreased TC levels (P < 0.05), and those with the B2 allele showed significantly lower triglyceride levels as compared to the subjects with the B1B1 homozygote (P < 0.05). TaqIB and D442G polymorphisms of the CETP gene did not independently affect the risk of developing EH in the Chinese Mongolian population, while the B2-G haplotype obviously decreased the susceptibility to EH. The B2 allele could alter the blood lipid level and reduce the risk of developing cardiovascular diseases. Show less
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequ Show more
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal. Transcription of CPS1 is suppressed by LKB1 through AMPK, and CPS1 expression correlates inversely with LKB1 in human NSCLC. Silencing CPS1 in KL cells induces cell death and reduces tumour growth. Notably, cell death results from pyrimidine depletion rather than ammonia toxicity, as CPS1 enables an unconventional pathway of nitrogen flow from ammonia into pyrimidines. CPS1 loss reduces the pyrimidine to purine ratio, compromises S-phase progression and induces DNA-polymerase stalling and DNA damage. Exogenous pyrimidines reverse DNA damage and rescue growth. The data indicate that the KL oncological genotype imposes a metabolic vulnerability related to a dependence on a cross-compartmental pathway of pyrimidine metabolism in an aggressive subset of NSCLC. Show less
A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in Show more
A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes ( Show less
Genome-wide association studies have struggled to identify functional genes and variants underlying complex phenotypes. We recruited a multi-ethnic cohort of healthy volunteers (n = 91) and used their Show more
Genome-wide association studies have struggled to identify functional genes and variants underlying complex phenotypes. We recruited a multi-ethnic cohort of healthy volunteers (n = 91) and used their tissue to generate induced pluripotent stem cells (iPSCs) and hepatocyte-like cells (HLCs) for genome-wide mapping of expression quantitative trait loci (eQTLs) and allele-specific expression (ASE). We identified many eQTL genes (eGenes) not observed in the comparably sized Genotype-Tissue Expression project's human liver cohort (n = 96). Focusing on blood lipid-associated loci, we performed massively parallel reporter assays to screen candidate functional variants and used genome-edited stem cells, CRISPR interference, and mouse modeling to establish rs2277862-CPNE1, rs10889356-DOCK7, rs10889356-ANGPTL3, and rs10872142-FRK as functional SNP-gene sets. We demonstrated HLC eGenes CPNE1, VKORC1, UBE2L3, and ANGPTL3 and HLC ASE gene ACAA2 to be lipid-functional genes in mouse models. These findings endorse an iPSC-based experimental framework to discover functional variants and genes contributing to complex human traits. Show less
Dual-specificity MAP kinase (MAPK) phosphatases (DUSPs) are well-established negative modulators in regulating MAPK signaling in mammalian cells and tissues. Our previous studies have shown the involv Show more
Dual-specificity MAP kinase (MAPK) phosphatases (DUSPs) are well-established negative modulators in regulating MAPK signaling in mammalian cells and tissues. Our previous studies have shown the involvement of DUSP6 in regulating innate immunity in Japanese flounder Paralichthys olivaceus. In order to gain a better understanding of the role of DUSPs in fish innate immunity, in the present study we identified and characterized three additional DUSP genes including DUSP1, 2 and 5 in P. olivaceus. The three Japanese flounder DUSP proteins share common domain structures composed of a conserved N-terminal Rhodanase/CDC25 domain and a C-terminal catalytic phosphatase domain, while they show only less than 26% sequence identities, indicating that they may have different substrate selectivity. In addition, mRNA transcripts of all the three DUSP genes are detected in all examined Japanese flounder tissues; however, DUSP1 is dominantly expressed in spleen while DUSP2 and 5 are primarily expressed in skin. Furthermore, all the three DUSP genes are constitutively expressed in the Japanese flounder head kidney macrophages (HKMs) and peripheral blood leucocytes (PBLs) with unequal distribution patterns. Moreover, all the three DUSPs gene expression was induced differently in response to the LPS and double-stranded RNA mimic poly(I:C) stimulations both in the Japanese flounder HKMs and PBLs, suggesting an association of DUSPs with TLR signaling in fish. Taken together, the co-expression of various DUSPs members together with their different responses to the immune challenges indicate that the DUSP members may operate coordinately in regulating the MAPK-dependent immune responses in the Japanese flounder. Show less
The Yangtze River Delta White Goat is the only goat breed that produces high-quality brush hair, or type III hair, which is specialized for use in top-grade writing brushes. There has been little rese Show more
The Yangtze River Delta White Goat is the only goat breed that produces high-quality brush hair, or type III hair, which is specialized for use in top-grade writing brushes. There has been little research, especially molecular research, on the traits that result in high-quality brush hair in the Yangtze River Delta White Goat. To explore the molecular mechanisms of the formation of high-quality brush hair, High-throughput RNA-Seq technology was used to compare skin samples from Yangtze River Delta White Goats that produce high-quality hair and non high-quality hair for identification of the important genes and related pathways that might influence the hair quality traits. The results showed that 295 genes were expressed differentially between the goats with higher and lower hair quality, respectively. Of those genes, 132 were up-regulated, 62 were down-regulated, and 101 were expressed exclusively in the goats with high-quality brush hair. Gene Ontology and Metabolic Pathway Significant Enrichment analyses of the differentially expressed genes indicated that the MAP3K1, DUSP1, DUSP6 and the MAPK signaling pathway might play important roles in the traits important for high-quality brush hair. Show less
Dual-specificity phosphatase 6 (Dusp6) is a member of mitogen-activated protein kinase (MAPK) phosphatases that play crucial roles in regulating MAPK signaling and immune response. The immunological r Show more
Dual-specificity phosphatase 6 (Dusp6) is a member of mitogen-activated protein kinase (MAPK) phosphatases that play crucial roles in regulating MAPK signaling and immune response. The immunological relevance of Dusp6 in fish, however, remains largely uncharacterized. In the present study, a full-length Japanese flounder dusp6 cDNA ortholog, termed PoDusp6, was identified and characterized from Paralichthys olivaceus. The deduced PoDusp6 protein is comprised of 383 amino acids with a conserved N-terminal regulatory rhodanese homology domain and a C-terminal catalytic domain. Immunofluorescence microscopy revealed that PoDusp6 protein is mainly localized in cytoplasm. Sequence analysis indicates that PoDusp6 is highly conserved (>70% identity) throughout the evolution from teleost to mammals. In unstimulated conditions, PoDusp6 mRNA was present in all examined tissues and showed the highest expression in Japanese flounder head kidney macrophages (HKMs). Immune challenge experiments revealed that the expression of PoDusp6 was down-regulated at the early stage after LPS and poly(I:C) stimulations but significantly up-regulated at the later stage in the HKMs. The similar expression pattern was also observed in the Japanese flounder immune-related tissues including head kidney, gill and spleen upon bacterial challenge with Edwardsiella tarda. Overexpression of PoDusp6 in Japanese flounder FG-9307 cells led to a significant down-regulation of proinflammatory cytokine genes IL-1beta, TNF-alpha and IFN-gamma, and antiviral gene Mx. Interestingly, inhibition of Dusp6 activity also down-regulated the LPS-induced IL-beta gene expression but did not affected on the LPS-induced IFN-gamma and TNF-alpha expression in the HKMs. Our findings suggest that the expression of PoDusp6 is modulated by immune stimuli and PoDusp6 may act as an essential modulator in fish inflammatory response. Show less
We present a case of post-traumatic endophthalmitis with relatively good prognosis caused by Gordonia sputi, which, to our knowledge is the first case in the literature. A 24 year old man, who underwe Show more
We present a case of post-traumatic endophthalmitis with relatively good prognosis caused by Gordonia sputi, which, to our knowledge is the first case in the literature. A 24 year old man, who underwent an intraocular foreign body extraction half a month before presentation in the left eye, was referred to us complaining of blurred vision and slight pain for 5 days. His first presentation showed moderate intracameral and intravitreous purulent inflammation with a best corrected vision of counting fingers. After gram staining of the intravitreous samples revealed a gram-positive bacilli infection, a combination of amikacin and vancomycin was initially injected intravitreously. The left eye kept stable for three days but deteriorated on the 4th day. On the 5th day after presentation conventional culture characterized the bacterium as an Actinomyces sp. while 16S ribosomal RNA gene sequencing confirmed it as Gordonia sputi. Thereby a complete pars plana vitrectomy combined with lensectomy and silicone oil tamponade was performed. During the surgery an intraocular irrigation with penicillin G was adopted, followed by administration of intravenous penicillin G twice one day for a week. A relatively normal fundus with slight intracameral inflammation was observed a week after the operation, and the best corrected vision recovered to 0.15. One year later his vision remained 0.1. Gordonia sputi should be taken into consideration in patients with post-traumatic endophthalmitis especially due to foreign body penetration. Compared to conventional laboratories, molecular methods are recommended for an accurate diagnosis. A comprehensive strategy of antimicrobial agents and vitrectomy may render a satisfactory result. Show less
Novel graphitic carbon nitride/CuO (g-C₃N₄/CuO) nanocomposite was synthesized through a facile precipitation method. Due to the strong ion-dipole interaction between copper ions and nitrogen atoms of Show more
Novel graphitic carbon nitride/CuO (g-C₃N₄/CuO) nanocomposite was synthesized through a facile precipitation method. Due to the strong ion-dipole interaction between copper ions and nitrogen atoms of g-C₃N₄, CuO nanorods (length 200-300 nm, diameter 5-10 nm) were directly grown on g-C₃N₄, forming a g-C₃N₄/CuO nanocomposite, which was confirmed via X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and X-ray photoelectron spectroscopy (XPS). Finally, thermal decomposition of ammonium perchlorate (AP) in the absence and presence of the prepared g-C₃N₄/CuO nanocomposite was examined by differential thermal analysis (DTA), and thermal gravimetric analysis (TGA). The g-C₃N₄/CuO nanocomposite showed promising catalytic effects for the thermal decomposition of AP. Upon addition of 2 wt % nanocomposite with the best catalytic performance (g-C₃N₄/20 wt % CuO), the decomposition temperature of AP was decreased by up to 105.5 °C and only one decomposition step was found instead of the two steps commonly reported in other examples, demonstrating the synergistic catalytic activity of the as-synthesized nanocomposite. This study demonstrated a successful example regarding the direct growth of metal oxide on g-C₃N₄ by ion-dipole interaction between metallic ions, and the lone pair electrons on nitrogen atoms, which could provide a novel strategy for the preparation of g-C₃N₄-based nanocomposite. Show less
The small GTPase Rab26 is involved in multiple processes, such as vesicle-mediated secretion and autophagy. However, the mechanisms and functions of Rab26 in the human pulmonary microvascular endothel Show more
The small GTPase Rab26 is involved in multiple processes, such as vesicle-mediated secretion and autophagy. However, the mechanisms and functions of Rab26 in the human pulmonary microvascular endothelial cells (HPMVECs) are not clear. In this study, we thoroughly investigated the role and novel mechanism of Rab26 in permeability and apoptosis of HPMVECs using a self-assembled Rab26 siRNA loaded DNA Y-motif nanoparticle (siRab26-DYM) and Rab26 adenovirus. We found that siRab26-DYM could be efficiently transfected into HPMVECs in a time- and dose-dependent manner. Importantly, the siRab26-DYM nanovector markedly aggravated the LPS-induced apoptosis and hyper-permeability of HPMVECs by promoting the nuclear translocation of Foxo1, and subsequent activation of Toll-like receptor 4 (TLR4) signal pathway. Overexpression of Rab26 by Rab26 adenoviruses partially inactivated LPS-induced TLR4 signaling pathway, suppressed the cell apoptosis and attenuated the hyperpermeability of HPMVECs. These results suggest that the permeability and apoptosis of HPMVECs can be modulated by manipulating Rab26 derived TLR4 signaling pathway, and that Rab26 can be potential therapeutic target for the treatment of vascular diseases related to endothelial barrier functions. Show less
Hereditary multiple exostoses (HME) is a rare autosomal dominant skeletal disorder that can cause a variety of clinical manifestations. We aimed to evaluate the general clinical phenotypic severity of Show more
Hereditary multiple exostoses (HME) is a rare autosomal dominant skeletal disorder that can cause a variety of clinical manifestations. We aimed to evaluate the general clinical phenotypic severity of HME by using a scoring system and correlate the genotypes with different clinical phenotypes in Chinese patients. Forty-six patients from different families were prospectively enrolled. The mutations were identified by direct sequencing of PCR-amplified genomic DNA or by multiplex ligation-dependent probe amplification (MLPA). Patients' demographic data, height, age of onset, number of anatomical sites, forearm deformity, and lower extremity alignment were analysed according to genotype and gender. A scoring system was used to assess the severity of the clinical phenotype. Thirty (60%) patients presented mutations in the EXT1 gene, and 16 (32%) presented mutations in the EXT2 gene. The mean age of onset was 2.96 years. The mean number of involved anatomic sites was 15.35. Male patients had more lesion sites than female patients (15.97 vs. 13.77, p = 0.046). The height evaluation illustrated that 67% of the patients (31 of 46) were below the 50th percentile, and the patients with EXT1 mutations were shorter than those with EXT2 mutations (p = 0.005). Forearm deformity showed a significant correlation with the number of involved anatomical sites (r = 0.382, p = 0.009). Moreover, a higher total score was found in patients with EXT1 mutations (p = 0.001). The clinical manifestations of 46 Chinese HME patients were similar to those in previous reports of Western populations. Patients with EXT1 mutations have a more severe clinical phenotype than patients with EXT2 mutations. Show less
Multiple osteochondromas (MO) is an autosomal skeletal disease with an elusive molecular mechanism. To further elucidate the genetic mechanism of the disease a three‑generation Chinese family with MO Show more
Multiple osteochondromas (MO) is an autosomal skeletal disease with an elusive molecular mechanism. To further elucidate the genetic mechanism of the disease a three‑generation Chinese family with MO was observed and researched, and a novel frameshift mutation (c.335₃₃₆insA) in the exotosin 1 (EXT1) gene of one patient with MO was observed through exome sequencing. This was further validated by Sanger sequencing and comparison with 200 unrelated healthy controls. Immunohistochemistry and multiple sequence alignment were performed to determine the pathogenicity of the candidate mutation. Multiple sequence alignment suggested that codon 335 and 336 in the EXT1 gene were highly conserved regions in vertebrates. Immunohistochemistry revealed that EXT1 protein expression levels were decreased in a patient with MO and this mutation compared with a patient with MO who had no EXT1 mutation. Owing to the appearance of c.335₃₃₆insA in exon 1 of EXT1, a premature stop codon was introduced, resulting in truncated EXT1. As a result integrated and functional EXT1 was reduced. EXT1 is involved in the biosynthesis of heparan sulfate (HS), an essential molecule, and its dysfunction may lead to MO. The novel mutation of c.335₃₃₆insA in the EXT1 gene reported in the present study has enlarged the causal mutation spectrum of MO, and may assist genetic counseling and prenatal diagnosis of MO. Show less
To develop a cost-effective molecular regulator to improve growth metabolism and immunity of animals, a recombinant plasmid co-expressing fatty acid desaturase (mFat-1) and pig insulin growth like fac Show more
To develop a cost-effective molecular regulator to improve growth metabolism and immunity of animals, a recombinant plasmid co-expressing fatty acid desaturase (mFat-1) and pig insulin growth like factor 1 (IGF-1) genes was constructed by the 2 A self-cleavage technique. After entrapment within modified chitosan nanoparticles (chitosan modified with polyethyleneglycol-polyethylenimine, CPP), the recombinant plasmid was injected intramuscularly into mice. Compared with controls, co-expression of mFat-1 and IGF-1 significantly raised the level of serum IGF-1, and increased the liver and muscle docosa hexaenoic acid (DHA) content. Th and Tc cell levels were also elevated, as were expression levels of serum IL-4 and IL-6 genes. These results demonstrate that the immunity and metabolism of an animal can be effectively improved by co-expression of mFat-1 and IGF-1 genes in vivo, which may contribute to further development of novel immunomodulators with beneficial effects on growth metabolism and immunity. Show less
The objective of this study was to investigate the effects of dietary n-6:n-3 PUFA ratio on growth performance, serum and tissue lipid levels, fatty acid profile, and hepatic expression of fatty acid Show more
The objective of this study was to investigate the effects of dietary n-6:n-3 PUFA ratio on growth performance, serum and tissue lipid levels, fatty acid profile, and hepatic expression of fatty acid synthesis genes in ducks. A total of 3168 15-day old ducks were fed different n-6:n-3 PUFA ratios: 13:1 (control), 10:1, 8:1, 6:1, 4:1, and 2:1. The feeding trial lasted 4 weeks. Our results revealed that dietary n-6:n-3 PUFA ratios had no effects on growth performance. The 2:1 group had the highest serum triglyceride levels. Serum total cholesterol and HDL levels were higher in the 13:1 and 8:1 groups than in the 6:1 and 2:1 groups. The concentration of C18:3n-3 in serum and tissues (liver and muscle) increased with decreasing dietary n-6:n-3 PUFA ratios. The hepatic expression of FADS2, ELOVL5, FADS1, and ELOVL2 increased on a quadratic function with decreasing dietary n-6:n-3 PUFA ratios. These results demonstrate that lower dietary n-6:n-3 PUFA ratios had strong effects on the fatty acid profile of edible parts and the deposition of n-3 PUFAs in adipose tissue of ducks. Show less
To identify novel candidate genes and gene sets for diabetes. We performed an integrative analysis of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) data for dia Show more
To identify novel candidate genes and gene sets for diabetes. We performed an integrative analysis of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) data for diabetes. Summary data was driven from a large-scale GWAS of diabetes, totally involving 58,070 individuals. eQTLs dataset included 923,021 cis-eQTL for 14,329 genes and 4,732 trans-eQTL for 2,612 genes. Integrative analysis of GWAS and eQTLs data was conducted by summary data-based Mendelian randomization (SMR). To identify the gene sets associated with diabetes, the SMR single gene analysis results were further subjected to gene set enrichment analysis (GSEA). A total of 13,311 annotated gene sets were analyzed in this study. SMR analysis identified 6 genes significantly associated with fasting glucose, such as C11ORF10 ( Our study provides novel clues for clarifying the genetic mechanism of diabetes. This study also illustrated the good performance of SMR approach and extended it to gene set association analysis for complex diseases. Show less
This study investigated the dietary effect of steam-pelleted rapeseed (RS) diets with different inclusion levels on the fatty acid composition of chicken meat and the expression of lipid metabolism-re Show more
This study investigated the dietary effect of steam-pelleted rapeseed (RS) diets with different inclusion levels on the fatty acid composition of chicken meat and the expression of lipid metabolism-related genes in the liver. Experimental diets included 6 different wheat-soybean meal based diets either in nonpelleted or steam-pelleted form supplemented with 80, 160, and 240 g RS/kg feed and one nonpelleted wheat-soybean meal based diet without RS supplementation as the control. These diets were fed to newly hatched broiler chickens (Ross 308) for 34 days. Compared to the control diet, steam-pelleted diets containing 160 or 240 g/kg RS significantly increased the content of omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) in the breast and drumstick, while their meat yields were not affected. Moreover, the mRNA levels of fatty acid desaturase 1 (FADS1) and acyl-coenzyme A oxidase 1 (ACOX1) in their livers increased. Therefore, steam-pelleted diets with 160 or 240 g/kg RS can be used to increase the n-3 LC-PUFA content in chicken meat without compromising meat yield. Show less
MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated Show more
MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 15,000 participants of Chinese and European ancestry. We identified novel genome-wide significant associations for vaccenic acid at Show less