2,016 research outputs found

    Cavernous Transformation of the Portal Vein Might Increase the Risk of Liver Abscess

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    Cavernous transformation of the portal vein (CTPV) is not quite common in adults, and cases with CTPV and acute liver abscess are lacking. We report a patient with CTPV inducing extrahepatic and intrahepatic obstruction, finally leading to acute liver abscess due to bile duct infection. We aim to find out the possible relationship between CTPV and acute liver abscess. A 45-year-old female patient was admitted to our hospital for recurrent upper abdominal pain and distension for one year, aggravated with fever for three years. A diagnosis of CTPV and liver abscess was made by 16-slice computed tomography. Effective antibiotics and drainage were used for this patients, and she was eventually cured. When treating patients with CTPV, extrahepatic and intrahepatic obstruction, one should be aware of the presence of acute liver abscess, and empirical antibiotics might be valuable

    Association between TGFBR1*6A and osteosarcoma: A Chinese case-control study

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    <p>Abstract</p> <p>Background</p> <p>TGFBR1*6A is a common hypomorphic variant of transforming growth factor β receptor 1 (TGFBR1). TGFBR1*6A is associated with an increased cancer risk, but the association of this polymorphism with osteosarcoma remains unknown. We have measured the frequency of TGFBR1*6A variants in osteosarcoma cases and controls.</p> <p>Methods</p> <p>Our case-control study is based on 168 osteosarcoma patients and 168 age- and gender-matched controls. Blood samples were obtained and the TGFBR1*6A variant determined by PCR amplification and DNA sequencing. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated by unconditional logistic regression, adjusted for both age and gender. Three models - dominant, additive and recessive - were used to analyze the contribution of the TGFBR1*6A variant to osteosarcoma susceptibility.</p> <p>Results</p> <p>Heterozygotic and homozygotic TGFBR1*6A variants represented 50.4% and 6.0% of the 168 cases, whereas the controls had 18. 5% and 1.3%, respectively. ORs for homozygosity and heterozygosity of the TGFBR1*6A allele were 4.6 [95% CI, 2.33-7.97] and 2.9 [95% CI, 1.59-5.34] in the additive model. There were significant increases in the TGFBR1*6A variants in osteosarcoma cases compared to control in all 3 models. Further analysis showed that TGFBR1*6A genotypes were not associated with gender, age, or tumor location. However, TGFBR1*6A was significantly associated with less metastasis.</p> <p>Conclusions</p> <p>TGFBR1*6A, a dominant polymorphism of TGFBR1, is associated with increased susceptibility and metastasis spread of osteosarcoma.</p

    Y Chromosomes of 40% Chinese Are Descendants of Three Neolithic Super-grandfathers

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    Demographic change of human populations is one of the central questions for delving into the past of human beings. To identify major population expansions related to male lineages, we sequenced 78 East Asian Y chromosomes at 3.9 Mbp of the non-recombining region (NRY), discovered >4,000 new SNPs, and identified many new clades. The relative divergence dates can be estimated much more precisely using molecular clock. We found that all the Paleolithic divergences were binary; however, three strong star-like Neolithic expansions at ~6 kya (thousand years ago) (assuming a constant substitution rate of 1e-9/bp/year) indicates that ~40% of modern Chinese are patrilineal descendants of only three super-grandfathers at that time. This observation suggests that the main patrilineal expansion in China occurred in the Neolithic Era and might be related to the development of agriculture.Comment: 29 pages of article text including 1 article figure, 9 pages of SI text, and 2 SI figures. 5 SI tables are in a separate ancillary fil

    Introducing a chaotic component in the control system of soil respiration

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    Chaos theory has been proved to be of great significance in a series of critical applications although, until now, its applications in analyzing soil respiration have not been addressed. This study aims to introduce a chaotic component in the control system of soil respiration and explain control complexity of this nonlinear chaotic system. This also presents a theoretical framework for better understanding chaotic components of soil respiration in arid land. A concept model of processes and mechanisms associated with subterranean CO2 evolution are developed, and dynamics of the chaotic system is characterized as an extended Riccati equation. Controls of soil respiration and kinetics of the chaotic system are interpreted and as a first attempt, control complexity of this nonlinear chaotic system is tackled by introducing a period-regulator in partitioning components of soil respiration

    Evolutional selection of a combinatorial phage library displaying randomly-rearranged various single domains of immunoglobulin (Ig)-binding proteins (IBPs) with four kinds of Ig molecules

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    <p>Abstract</p> <p>Background</p> <p>Protein A, protein G and protein L are three well-defined immunoglobulin (Ig)-binding proteins (IBPs), which show affinity for specific sites on Ig of mammalian hosts. Although the precise functions of these molecules are not fully understood, it is thought that they play an important role in pathogenicity of bacteria. The single domains of protein A, protein G and protein L were all demonstrated to have function to bind to Ig. Whether combinations of Ig-binding domains of various IBPs could exhibit useful novel binding is interesting.</p> <p>Results</p> <p>We used a combinatorial phage library which displayed randomly-rearranged various-peptide-linked molecules of D and A domains of protein A, designated PA(D) and PA(A) respectively, B2 domain of protein G (PG) and B3 domain of protein L (PL) for affinity selection with human IgG (hIgG), human IgM (hIgM), human IgA (hIgA) and recombinant hIgG1-Fc as bait respectively. Two kinds of novel combinatorial molecules with characteristic structure of PA(A)-PG and PA(A)-PL were obtained in hIgG (hIgG1-Fc) and hIgM (hIgA) post-selection populations respectively. In addition, the linking peptides among all PA(A)-PG and PA(A)-PL structures was strongly selected, and showed interestingly divergent and convergent distribution. The phage binding assays and competitive inhibition experiments demonstrated that PA(A)-PG and PA(A)-PL combinations possess comparable binding advantages with hIgG/hIgG1-Fc and hIgM/hIgA respectively.</p> <p>Conclusion</p> <p>In this work, a combinatorial phage library displaying Ig-binding domains of protein A, protein G, or protein L joined by various random linking peptides was used to conducted evolutional selection <it>in vitro</it> with four kinds of Ig molecules. Two kinds of novel combinations of Ig-binding domains, PA(A)-PG and PA(A)-PL, were obtained, and demonstrate the novel Ig binding properties.</p

    The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation.

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    Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation

    Seminal Plasma Metabolome in Relation to Semen Quality and Urinary Phthalate Metabolites Among Chinese Adult Men

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    Background: A growing body of evidence has found links between endocrine disruptor phthalates and male reproductive disorders, but the mechanisms underlying these relationships are poorly known. Seminal plasma metabolomes may mediate associations of phthalate exposure with impaired semen quality. Objective: To identify seminal plasma metabolomes associated with poor semen quality and evaluate their associations with urinary phthalate metabolites among 660 Chinese adult men. Method: The seminal plasma metabolic profiles were acquired using an untargeted approach based on liquid chromatography-high resolution mass spectrometry. We explored the differences in seminal plasma metabolites between participants with poor and good semen quality and evaluated cross-sectional associations between discriminatory metabolic biomarkers and urinary phthalate metabolites. Results: Differences between poor and good semen quality groups were observed in relation to 25 seminal plasma metabolites, mostly related to the metabolism of polyunsaturated fatty acids (PUFA) and acylcarnitine (all p \u3c 0.05). After adjusting for various confounders and multiple tests, metabolites were all significantly associated with one or more individual sperm quality parameters (motility, concentration, total count, and morphology) (all p \u3c 0.05). Among identified metabolic biomarkers, seminal plasma L-palmitoylcarnitine, linoelaidyl carnitine, and oleic acid were inversely associated with urinary mono-(2-ethylhexyl) phthalate (MEHP), and seminal plasma L-acetylcarnitine was inversely associated with the proportion of di-(2-ethylhexyl)-phthalate metabolites (DEHP) excreted as MEHP in urine (%MEHP) (all p \u3c 0.05). Mediation analysis revealed that oleic acid and L-acetylcarnitine mediated significant proportions (6.7% and 17%, respectively) of the positive associations between urinary DEHP metabolites and the percentage of spermatozoa with an abnormal head. Conclusions: Elevated urinary phthalate metabolites may impact semen quality by causing metabolic disorders of seminal plasma PUFAs and acylcarnitine. These pathways warrant further investigation

    Exosomes in osteoarthritis: Updated insights on pathogenesis, diagnosis, and treatment

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    Osteoarthritis (OA) has remained a prevalent public health problem worldwide over the past decades. OA is a global challenge because its specific pathogenesis is unclear, and no effective disease-modifying drugs are currently available. Exosomes are small and single-membrane vesicles secreted via the formation of endocytic vesicles and multivesicular bodies (MVBs), which are eventually released when MVBs fuse with the plasma membrane. Exosomes contain various integral surface proteins derived from cells, intercellular proteins, DNAs, RNAs, amino acids, and metabolites. By transferring complex constituents and promoting macrophages to generate chemokines and proinflammatory cytokines, exosomes function in pathophysiological processes in OA, including local inflammation, cartilage calcification and degradation of osteoarthritic joints. Exosomes are also detected in synovial fluid and plasma, and their levels continuously change with OA progression. Thus, exosomes, specifically exosomal miRNAs and lncRNAs, potentially represent multicomponent diagnostic biomarkers for OA. Exosomes derived from various types of mesenchymal stem cells and other cell or tissue types affect angiogenesis, inflammation, and bone remodeling. These exosomes exhibit promising capabilities to restore OA cartilage, attenuate inflammation, and balance cartilage matrix formation and degradation, thus demonstrating therapeutic potential in OA. In combination with biocompatible and highly adhesive materials, such as hydrogels and cryogels, exosomes may facilitate cartilage tissue engineering therapies for OA. Based on numerous recent studies, we summarized the latent mechanisms and clinical value of exosomes in OA in this review

    Targeting Gpr52 lowers mutant HTT levels and rescues Huntington's disease-associated phenotypes.

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    See Huang and Gitler (doi:10.1093/brain/awy112) for a scientific commentary on this article.Lowering the levels of disease-causing proteins is an attractive treatment strategy for neurodegenerative disorders, among which Huntington's disease is an appealing disease for testing this strategy because of its monogenetic nature. Huntington's disease is mainly caused by cytotoxicity of the mutant HTT protein with an expanded polyglutamine repeat tract. Lowering the soluble mutant HTT may reduce its downstream toxicity and provide potential treatment for Huntington's disease. This is hard to achieve by small-molecule compound drugs because of a lack of effective targets. Here we demonstrate Gpr52, an orphan G protein-coupled receptor, as a potential Huntington's disease drug target. Knocking-out Gpr52 significantly reduces mutant HTT levels in the striatum and rescues Huntington's disease-associated behavioural phenotypes in a knock-in Huntington's disease mouse model expressing endogenous mutant Htt. Importantly, a novel Gpr52 antagonist E7 reduces mutant HTT levels and rescues Huntington's disease-associated phenotypes in cellular and mouse models. Our study provides an entry point for Huntington's disease drug discovery by targeting Gpr52

    The Physical Properties of Star-Forming Galaxies with Strong [O III] Lines at z=3.25

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    We present an analysis of physical properties of 34 [O III] emission-line galaxies (ELGs) at z=3.254±\pm0.029 in the Extended Chandra Deep Field South (ECDFS). These ELGs are selected from deep narrow H2S(1) and broad Ks imaging of 383 arcmin2^{2} obtained with CFHT/WIRCam. We construct spectral energy distributions (SEDs) from U to Ks to derive the physical properties of ELGs. These [O III] ELGs are identified as starburst galaxies with strong [O III] lines of L([O III]) ~ 1042.6^{42.6} - 1044.2^{44.2} erg s1^{-1}, and have stellar masses of M* ~ 109.0^{9.0}-1010.6^{10.6} M_\odot and star formation rates of ~ 10-210 M_\odot yr1^{-1}. Our results show that 24% of our sample galaxies are dusty with Av > 1 mag and EW(OIII)rest_{rest} ~ 70-500 A˚\AA, which are often missed in optically selected [O III] ELG samples. Their rest-frame UV and optical morphologies from HST/ACS and HST/WFC3 deep imaging reveal that these [O III] ELGs are mostly multiple-component systems (likely mergers) or compact. And 20% of them are nearly invisible in the rest-frame UV owing to heavy dust attenuation. Interestingly, we find that our samples reside in an overdensity consisting of two components: one southeast (SE) with an overdensity factor of δgal\delta_{gal} ~ 41 over a volume of 133^{3} cMpc3^{3} and the other northwest (NW) with δgal\delta_{gal} ~ 38 over a volume of 103^{3} cMpc3^{3}. The two overdense substructures are expected to be virialized at z=0 with a total mass of ~ 1.1 x 1015^{15} M_\odot and ~ 4.8 x 1014^{14} M_\odot, and probably merge into a Coma-like galaxy cluster.Comment: 22 pages, 11 figures, 3 tables. Accepted for publication in Ap
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