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1.
Small ; 16(6): e1905876, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31962381

RESUMO

Osteogenesis, osteoclastogenesis, and angiogenesis are the most important processes in bone repair. Parathyroid hormone (PTH) has pro-osteogenic, pro-osteoclastogenic, and proangiogenic effects and may be a candidate for use in bone defect repair. However, the local application of PTH to bone defects is counterproductive due to its excessive osteoclastic and bone resorptive effects. In this study, a PTH derivative, PTHrP-2, is developed that can be applied to local bone defects. First, a modified peptide with a calcium-binding repeat glutamine tail undergoes controlled local release from a ceramic material and is shown to be a better fit for the repair process than the unmodified peptide. Second, the modified peptide is shown to have strong pro-osteogenic activity due to mineralization and its facilitation of serine (Ser) phosphorylation. Third, the modified peptide is shown to maintain the pro-osteoclastogenic and proangiogenic properties of the unmodified peptide, but its pro-osteoclastogenic activity is reduced compared to that of the unmodified peptide. The reduced pro-osteoclastogenic and increased pro-osteogenic properties of the modified peptide reverse the imbalance between osteoblasts and osteoclasts with local PTH application and shift bone resorption to bone regeneration.

2.
Environ Pollut ; 257: 113543, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31753634

RESUMO

Aquaculture can affect the polyunsaturated fatty acids (PUFA) and mercury (Hg) in fish by altering their diet. Here, planktivorous (silver carp and bighead carp), omnivorous and carnivorous fish with different dietary strategies were selected from two reservoirs, one with on-going aquaculture (WJD) and another without aquaculture (HF) in Southwest China. We compared the total mercury (THg), methylmercury (MeHg) contents and PUFA profiles of fish and their potential diets in these two reservoirs. THg and MeHg contents in omnivorous and carnivorous fish were lower from the WJD Reservoir, which is related to the lower THg and MeHg contents in the artificial fish food. THg and MeHg contents in silver carp from the WJD Reservoir were lower than those from the HF Reservoir, while they were similar in bighead carps from the two reservoirs. The Hg variation in planktivorous fish were inconsistent with that in plankton. THg contents in phyto- and zooplankton from the HF Reservoir were higher than those from the WJD Reservoir, yet their MeHg contents were similar. Artificial fish food which contained higher total PUFA eicosapentaenoic (EPA; 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), significantly increased the total PUFA and EPA + DHA contents in carnivorous fish, but had less effect on that in omnivorous fish from the WJD Reservoir. Eutrophication caused by aquaculture reduced total PUFA and EPA + DHA contents of plankton in WJD, yet did not reduce those in planktivorous fish. The impacts of aquaculture on Hg and PUFA accumulated in fish were varied among different fish species, and the mechanism needs further exploration.

3.
Int J Pharm ; 575: 118943, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31830575

RESUMO

Self-assembly of drug-polysacrrides conjugates forming nanostructures provides a simple and promising strategy for the extension of precorneal retention and enhancement of corneal permeability. In the present study, a series of dexamethasone-glycol chitosan (Dex-GCS) conjugates were synthesized and thoroughly characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and ultraviolet-visible (UV-Vis) spectroscopy. The resulting Dex-GCS conjugates were able to self-assemble into nanoparticles spontaneously with particle sizes in the range of 277-289 nm and a positive charge of approximately +15 mV. Roughly spherical nanoparticles were observed by transmission electron microscopy (TEM). The in vitro mucoadhesive properties of Dex-GCS nanoparticles were evaluated by recording the variations in the zeta potential after incubation with different concentrations of mucin. In vitro release studies performed in phosphate-buffered saline (PBS, pH = 7.4) indicated progressive Dex release up to 8 h, followed by a plateau up to 48 h. Dex-GCS nanoparticles caused slight cytotoxicity against L929, HCEC and RAW 264.7 cells after 24 h of incubation and displayed a nearly identical anti-inflammatory efficacy to dexamethasone sodium phosphate (Dexp) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. More importantly, the proposed Dex-GCS nanoparticles showed good ocular tolerance and provided a relatively longer precorneal duration compared with that of the aqueous solution formulation, which suggested that the self-assembled Dex-GCS nanoparticle might be a promising candidate for ophthalmic drug delivery.

4.
Ocul Immunol Inflamm ; 28(1): 133-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30395736

RESUMO

Purpose: To investigate whether there is an association between circulating S100A8/A9 levels and uveitis activity.Methods: A total of 549 plasma samples were collected from uveitis patients and non-uveitic controls.Results: S100A8/A9 plasma levels were elevated in uveitis patients compared to non-uveitic controls (P < 0.001). S100A8/A9 plasma levels in patients with active acute anterior uveitis (AAU) were significantly elevated and remarkably decreased in parallel with the severity of intraocular inflammation after corticosteroid treatment (P < 0.001). S100A8/A9 plasma levels were also higher in AAU patients with ankylosing spondylitis (AS) than in patients without AS (P = 0.02). S100A8/A9 plasma levels were significantly increased in uveitis patients with elevated C-reactive protein (CRP, P = 0.004) or erythrocyte sedimentation rates (ESR, P = 0.049) levels compared to uveitis patients with normal CRP or ESR values.Conclusion: Circulating S100A8/A9 might be a useful biomarker for the measurement of intraocular inflammation.

5.
Dent Mater ; 36(2): 320-328, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31864675

RESUMO

OBJECTIVE: This study aims to evaluate sequence-modified Ti surfaces functionalized with silanized glutaraldehyde and further grafted with the active biomolecules of phosphatidylcholine and type I collagen (COL I). METHODS: The properties of the functional surfaces were investigated by various surface analysis techniques and characterized their capability in osteogenic cell attachment, differentiation, and mineralization in vitro. RESULTS: The Ti surfaces grafted with phosphatidylcholine and COL I effectively improved the hydrophilicity. In addition, an effect of COL I concentrations (higher than 2.5µg/mL) do not stimulate subsequent alkaline phosphatase (ALP) activity during osteogenesis in vitro. However, the result is different in phosphatidylcholine, that is, as the concentration of phosphatidylcholine increased enhances subsequent osteogenetic properties. The Ti groups with bioactive molecules affected cell characteristics in vitro in contrast to the controlled Ti group. The proliferation and differentiation levels of osteoprogenetor cells were enhanced and ALP was strongly expressed in the groups grafted with phosphatidylcholine and COL I. SIGNIFICANCE: This modification promotes progenitor bone cell adhesion, proliferation, and differentiation and thus drastically improves the success rate for implant modification by accelerating surface osseointegration.

6.
Mater Sci Eng C Mater Biol Appl ; 107: 110204, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761242

RESUMO

Using a novel microwave-assisted hydrothermal (MW) process we created nano-scale anatase on micro-arc-oxidized (MAO) titanium surface. The morphology/crystallinity and surface potential of the anatase which altered by Ca/P ions concentrations and pH in the MW medium were characterized by atomic force microscopy, Kelvin probe force microscopy, Raman spectrometer, and x-ray photoelectron spectroscopy. The surface of MWDD (processed in DD water) and MWCP (in neutral pH medium with Ca/P ions) are covered with anatase spikes, which enhance their nano-roughness, hydrophilicity, and possess lower surface potential than other groups. The nano-precipitates on surface of MWCP9 and MWCP11 (processed in medium containing Ca/P ions at pH 9 or pH 11) were mainly amorphous anatase with less P ions. The protein adsorption of negatively charged bovine serum albumin was higher in MWDD and MWCP groups which possess lower surface potential. The adsorption of positively charged histones on the surface of MWCP11 was higher compared to the other groups. The osteogenic characterizations of D1 mice bone marrow mesenchymal stem cells co-cultured for 1, 7, and 14 days were measured by ALP and osteopontin assays. Although MW groups revealed comparable viability of D1 mice bone marrow mesenchymal stem cells to MAO group, their superior hydrophilicity and higher protein adsorption, thus regulating the differentiation of osteoprogenitor stem cells demonstrating higher ALP and osteopontin secretion after 7 days and 14 days. The nanoscale topography, crystallinity and surface potential change the hydrophilicity and protein adsorption on the MW treated titanium surface, thus regulating the differentiation of osteoprogenitor stem cells in vitro.

7.
Am J Cancer Res ; 9(11): 2314-2330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815037

RESUMO

Zinc finger E-box binding homeobox 1 (ZEB1), as a typical transcription inhibitory factor of E-cadherin, plays a major role in stimulating the invasion and metastasis of tumors via modulating the epithelial-mesenchymal transition (EMT) signal. However, its function and modulatory mechanisms in endometrial carcinoma (EC) remain unclear. In this study, silencing ZEB1 significantly reduced EC cell migration, invasion, and metastasis, as well as enhanced the sensitivity of EC cells to cisplatin (cDDP) in vitro and in vivo. Mechanism analysis indicated that ZEB1 interacts with hepatoma-derived growth factor (HDGF) and co-localizes in the nucleus. In addition, ZEB1 as a transcription factor binds to the promoter of HDGF to stimulate HDGF transcription. Furthermore, suppression of HDGF in ZEB1-overexpressed EC cells not only reduced the expression of ß-catenin, TCF4, and ZEB1, but also repressed ß-catenin translocation from the cytoplasm into the nucleus and further downregulated the combination with TCF4. Interestingly, the ß-catenin/TCF4 signaling feedback stimulates ZEB1 transcription and therefore constitutes a positive feedback loop. In clinical samples, ZEB1 positively correlates with HDGF expression, and co-expression of ZEB1 and HDGF promotes the pathogenesis of EC. In summary, our study demonstrated that the positive feedback loop of ZEB1/HDGF/ß-catenin/TCF4 plays an unfavorable role in the metastasis of endometrial carcinoma.

8.
Eye (Lond) ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31844164

RESUMO

PURPOSE: To investigate the association between serum amyloid A (SAA) protein and the clinical features of acute anterior uveitis (AAU), and to evaluate the disease activity and treatment effect in relation to SAA levels. METHODS: AAU patients and healthy individuals were recruited from October 2016 to August 2017 at the Department of Uveitis, in the Eye Hospital of Wenzhou Medical University. Related demographic, clinical characteristics, and therapeutic data were analyzed. RESULTS: One hundred and eight AAU patients and 18 healthy controls were included in this study. Serum SAA levels in AAU patients were significantly higher than those of healthy controls (p all < 0.0001). Significantly higher SAA levels were found in AS+AAU patients than those in AS-AAU patients (p < 0.05). SAA levels were also significantly higher in patients with HLA-B27+AAU compared with those with HLA-B27-AAU (p < 0.05). Furthermore, in each of the AAU subgroups, higher SAA levels were observed in the active state than those in the inactive state (p all < 0.05). In addition, SAA levels were positively correlated to anterior chamber cell counts (r = 0.492, p < 0.0001). ROC curve analysis revealed that SAA had an AUC value of 0.727 for detecting active inflammation (Youden's index = 0.38). SAA decreased with effective treatments (p = 0.0002). CONCLUSION: Serum levels of SAA were elevated in AAU patients. The increased levels of SAA were correlated with AS and HLA-B27 status. SAA levels were also positively correlated to disease activity and decreased with effective treatments. These findings suggest that SAA is associated with AAU, with a potential role in monitoring inflammatory processes and assessing the efficacy of therapy.

9.
Mar Genomics ; : 100722, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31677976

RESUMO

Marine Bacteroidetes are well known for their functional specialization on the decomposition of polysaccharides which results from a great number of carbohydrate-active enzymes. Here we represent the complete genome of a Bacteroitedes member Echinicola rosea JL3085T that was isolated from surface seawater of the South China Sea. The genome is 6.06 Mbp in size with a GC content of 44.1% and comprises 4613 protein coding genes. A remarkable genomic feature is that the number of glycoside hydrolase genes in the genome of E. rosea JL3085T is high in comparison with most of the sequenced members of marine Bacteroitedes. E. rosea JL3085T genome harbored multi-gene polysaccharide utilization loci (PUL) systems involved in the degradation of pectin, xylan and arabinogalactan. The large diversity of hydrolytic enzymes supports the use of E. rosea JL3085T as a candidate for biotechnological applications in enzymatic conversion of plant polysaccharides.

10.
Inorg Chem ; 58(22): 15401-15409, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31674179

RESUMO

A new iron-base superconductor SmFFeAs is synthesized via solid-state metathesis reaction by using SmFCl and LiFeAs as precursors. The compound crystallized in the tetragonal ZrCuSiAs-type structure with the space group P4/nmm and lattice parameters of a = 3.9399(0) Å and c = 8.5034(1) Å. The superconducting diamagnetic transition occurs at 56 K for the parent compound, which confirmed by the resistivity and magnetic susceptibility. The appearance of superconductivity without extrinsic doping could be ascribed to the self-doping owing to the mixed valence of Sm ions. The as-synthesized SmFFeAs serves as a new self-doped parent compound for oxygen-free high-critical-temperature (high-Tc) superconductors.

11.
Front Psychol ; 10: 2397, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708837

RESUMO

The present study examined developmental changes, over a 6-year period, in the relationship between character reading ability and orthographic awareness in Chinese from the first year of kindergarten to the third year of primary school in two separate samples: the kindergarten sample of 96 children was assessed three times in the first, second, and third years of kindergarten (K1, K2, K3) with 12-month intervals. The primary school sample of 204 children was assessed four times in the first and second semesters of grade 1 (P1-S1; P1-S2), first semester of grade 2 (P2-S1) and grade 3 (P3-S1), with the first three waves at 6-month intervals and the final wave at 12-month interval. Cross-lagged path analysis showed three developmental stages of the relationship between Chinese character reading and orthographic awareness. At stage 1, reading ability in K1 and K2 predicted subsequent orthographic awareness in K2 and K3. At stage 2, there was a bidirectional relationship between character reading and orthographic awareness from P1-S1 to P1-S2. At stage 3, orthographic awareness at P1-S2 and P2-S1 predicted subsequent character reading ability at P2-S1 and P3-S1, but the prediction from reading to orthographic awareness vanished at this stage. The results depict a full developmental picture of the changed relationship between Chinese character reading and orthographic awareness over time. Beginning readers demonstrated impressive abilities in discovering or extracting orthographic regularities with increased reading ability.

12.
Front Psychol ; 10: 2407, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708844

RESUMO

Playing chess requires perspective taking in order to consistently infer the opponent's next moves. The present study examined whether long-term chess players are more advanced in visual perspective taking tasks than their counterparts without chess training during laboratory visual perspective taking tasks. Visual perspective taking performance was assessed among 11- to 12-year-old experienced chess players (n = 15) and their counterparts without chess training (n = 15) using a dot perspective task. Participants judged their own and the avatar's visual perspective that were either consistent with each other or not. The results indicated that the chess players out-performed the non-chess players (Experiment 1), yet this advantage disappeared when the task required less executive functioning (Experiment 2). Additionally, unlike the non-chess players whose performance improved in Experiment 2 when the executive function (EF) demand was reduced, the chess players did not show better perspective taking under such condition. These findings suggested that long-term chess experience might be associated with children's more efficient perspective taking of other people's viewpoints without exhausting their cognitive resources.

13.
Int J Nanomedicine ; 14: 6691-6706, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692515

RESUMO

Purpose: Amentoflavone, robustaflavone, 2'',3''-dihydro-3',3'''-biapigenin, 3',3'''-binaringenin and delicaflavone are five major active ingredients in the total biflavonoids extract from Selaginella doederleinii (TBESD) with favorable anticancer properties. However, the natural-derived potent antitumor agent of TBESD is undesirable due to its poor solubility. The present study was to develop and optimize a proliposomal formulation of TBESD (P-TBESD) to improve its solubility, oral bioavailability and efficacy. Materials and methods: P-TBESD containing a bile salt, a protective hydrophilic isomalto-oligosaccharides (IMOs) coating, were successfully prepared by thin film dispersion-sonication method. The physicochemical and pharmacokinetic properties of P-TBESD were characterized, and the antitumor effect was evaluated using the HT-29 xenograft-bearing mice models in rats. Results: Compared with TBESD, the relative bioavailability of amentoflavone, robustaflavone, 2'',3''-dihydro-3',3'''-biapigenin, 3',3'''-binaringenin and delicaflavone from P-TBESD were 669%, 523%, 761%, 955% and 191%, respectively. The results of pharmacodynamics demonstrated that both TBESD and P-TBESD groups afforded antitumor effect without systemic toxicity, and the antitumor effect of P-TBESD was significantly superior to that of raw TBESD, based on the tumor growth inhibition and histopathological examination. Conclusion: Hence, IMOs-modified proliposomes have promising potential for TBESD solving the problem of its poor solubility and oral bioavailability, which can serve as a practical oral preparation for TBESD in the future cancer therapy.

14.
Front Oncol ; 9: 1139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737568

RESUMO

Background: There was rare studies on prognosis of pulmonary venous CTC and early or advanced NSCLC patients. We want to investigate whether CTCs and the subtype of it can predict the prognosis of NSCLC patients. Patients and Methods: One hundred and fourteen patients with stage I-III NSCLC were included CanPatrol™ CTC analysis. PD-L1 expression level were detected in CTC of pulmonary vein. PD-L1, number of CTC in pulmonary, CTC's subtype, clinical characteristics, prognosis of patients were analyzed. Results: 110/114 (96.5%) patients could be found CTCs in pulmonary vein, 58/114 (50.9%) patients had CTC≥15/ml in pulmonary vein, 53/110 patients (48.2%) were defined as having MCTC subtype and 56/110 patient were found have PD-L1 (+) CTC in pulmonary vein. Multivariate analyses showed that PVCTC, MCTC, and stage were independent factors of DFS (P < 0.05). No OS difference was found between number of CTC (P = 0.33) and other CTC factors (P > 0.05), only stage was independent factor of OS (P = 0.019). There were decreases of CTC number and MCTC number in EGFR mutant subgroup (P = 0.0009 and P = 0.007). There were increases of CTC (P = 0.0217), MCTC (P = 0.0041), and PD-L1 (+) CTC (P = 0.0002) number in KRAS mutant subgroup. There was increase of MCTC (P =0.0323) number in BRAF mutant. There were fewer CTCs in pulmonary vein for patients with EGFR mutant than in patients with full wild-type gene (P = 0.0346). There were more PD-L1 positive CTCs in pulmonary vein for patients with ALK rearrangement, KRAS mutant, BRAF mutant, or ROS1 mutant than in patients with full wild-type gene (P = 0.0610, P = 0.0003, P = 0.032, and P = 0.0237). There were more mesenchymal CTCs in pulmonary vein for patients with KRAS mutant and BRAF mutant than in patients with full wild-type gene (P = 0.073 and P = 0.0381). There were fewer mesenchymal CTCs in pulmonary vein for patients with EGFR mutant than in patients with full wild-type gene (P = 0.0898). Conclusions: The patients with high number of CTCs, MCTCs, or PD-L1 (+) CTCs in pulmonary vein experienced poor prognosis of DFS. There are obvious correlations between the CTC subtype of NSCLC and the gene subgroups of tumor tissue.

15.
Stat Med ; 38(30): 5603-5622, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31659784

RESUMO

The literature about Prediction Interval (PI) and Tolerance Interval (TI) in linear mixed models is usually developed for specific designs, which is a main limitation to their use. This paper proposes to reformulate the two-sided PI to be generalizable under a wide variety of designs (one random factor, nested and crossed designs for multiple random factors, and balanced or unbalanced designs). This new methodology is based on the Hessian matrix, namely, the inverse of (observed) Fisher Information matrix, and is built with a cell mean model. The degrees of freedom for the total variance are calculated with the generalized Satterthwaite method and compared to the Kenward-Roger's degrees of freedom for fixed effects. Construction of two-sided TIs are also detailed with one random factor, and two nested and two crossed random variables. An extensive simulation study is carried out to compare the widths and coverage probabilities of Confidence Intervals (CI), PIs, and TIs to their nominal levels. It shows excellent coverage whatever the design and the sample size are. Finally, these CIs, PIs, and TIs are applied to two real data sets: one from orthopedic surgery study (intralesional resection risk) and the other from assay validation study during vaccine development.

16.
Materials (Basel) ; 12(19)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31574919

RESUMO

This study aims to investigate the shear bonding strength (SBS) and thermal cycling effect of orthodontic brackets bonded with fluoride release/rechargeable LiAl-F layered double hydroxide (LDH-F) contained dental orthodontic resin. 3% and 5% of LDH-F nanopowder were gently mixed to commercial resin-based adhesives Orthomite LC (LC, LC3, LC5) and Transbond XT (XT, XT3). A fluoroaluminosilicate modified resin adhesive Transbond color change (TC) was selected as a positive control. Fifteen brackets each group were bonded to bovine enamel and the SBS was tested with/without thermal cycling. The adhesive remnant index (ARI) was evaluated at 20× magnification. The fluoride-releasing/rechargeability and cytocompatibility were also evaluated. The SBS of LC, LC3, and LC5 were significantly higher than XT and TC. After thermal cycling, the SBS of LC, LC3, and LC5 did not decrease and was significantly higher than TC. The changes of ARI scores indicate that failure occurred not only cohesive but also semi-cohesive fracture. The 30 days accumulated daily fluoride release of LC3, LC5, and TC without recharge are higher than 300 µg/cm2. The LDH-F contained resin adhesive possesses higher SBS compared to positive control TC. Fluoride release and the rechargeable feature can be achieved for preventing enamel demineralization without cytotoxicity.

17.
Front Oncol ; 9: 862, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572671

RESUMO

OTUD7B, a multifunctional deubiquitinylase, plays an essential role in inflammation and proliferation signals. However, its function in lung cancer remains largely unknown. The aim of this study was to evaluate the prognostic significance of OTUD7B in patients with lung adenocarcinoma and squamous carcinoma and to characterize its molecular mechanisms in lung cancer progression and metastasis. Two tissue microarrays containing 150 pairs of lung squamous carcinoma and matched adjacent non-cancer tissues, and one tissue microarray containing 75 pairs of lung adenocarcinoma and adjacent non-cancer tissues were included, and immunohistochemical staining was performed to assess the clinical relevance of OTUD7B in non-small cell lung cancer. OTUD7B is highly expressed in both lung squamous carcinoma and adenocarcinoma and correlates with a worse prognosis. MTT proliferation, colony formation, migration and invasion assays and immunoblotting assay in NCI-H358 and A549 cell lines suggested that OTUD7B enhances EGF-induced Akt signal transduction and promotes lung cancer cell proliferation and migration. Immunohistochemical staining of large-scale lung cancer subjects (171 cases) revealed positive correlation of OTUD7B and VEGF expression. ELISA and tube formation assay revealed OTUD7B promotes VEGF production and angiogenesis. NCI-H358 tumor model demonstrated OTUD7B is required for lung tumor progression by facilitating activation of Akt signaling. These findings collectively identified OTUD7B as an independent predictive factor for the prognosis of non-small cell lung cancer and revealed OTUD7B promotes lung cancer cell proliferation and metastasis via Akt/VEGF signal pathway.

18.
Am J Hum Genet ; 105(4): 773-787, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564431

RESUMO

Genome-wide association studies (GWASs) have identified thousands of genetic loci associated with cardiometabolic traits including type 2 diabetes (T2D), lipid levels, body fat distribution, and adiposity, although most causal genes remain unknown. We used subcutaneous adipose tissue RNA-seq data from 434 Finnish men from the METSIM study to identify 9,687 primary and 2,785 secondary cis-expression quantitative trait loci (eQTL; <1 Mb from TSS, FDR < 1%). Compared to primary eQTL signals, secondary eQTL signals were located further from transcription start sites, had smaller effect sizes, and were less enriched in adipose tissue regulatory elements compared to primary signals. Among 2,843 cardiometabolic GWAS signals, 262 colocalized by LD and conditional analysis with 318 transcripts as primary and conditionally distinct secondary cis-eQTLs, including some across ancestries. Of cardiometabolic traits examined for adipose tissue eQTL colocalizations, waist-hip ratio (WHR) and circulating lipid traits had the highest percentage of colocalized eQTLs (15% and 14%, respectively). Among alleles associated with increased cardiometabolic GWAS risk, approximately half (53%) were associated with decreased gene expression level. Mediation analyses of colocalized genes and cardiometabolic traits within the 434 individuals provided further evidence that gene expression influences variant-trait associations. These results identify hundreds of candidate genes that may act in adipose tissue to influence cardiometabolic traits.

19.
Mater Sci Eng C Mater Biol Appl ; 105: 110074, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546393

RESUMO

Hydrogel membranes are often used as physical barriers in oral tissue reconstruction and facial surgery to isolate connective and epithelial tissues and form a closed space for undisturbed bone healing. In this study, gelatin and hyaluronic acid were crosslinked with genipin and loaded with a hinokitiol additive as a bacteriostatic agent for potential applications as regeneration membranes. This bifunctional membrane had biocompatibility and antibacterial activities on each membrane side for proper biodegradation. Different membrane groups of gelatin/hyaluronic acid were obtained via a solution casting technique and were genipin crosslinked. The membrane groups were further loaded with adequate hinokitiol at a loading concentration of up to 0.16 g/L (hinokitiol to phosphate buffered saline). Fourier transform infrared spectroscopy showed that gelatin and hyaluronic acid were crosslinked with genipin through cross-linking amide bond (CONH) formation with a cross-linking degree of over 84%. The groups with hinokitiol showed substantial antibacterial activity. Meanwhile, the addition of hinokitiol on hydrogel membranes did not significantly affect the tensile strength. However, it decreased the solubility of the membranes by slowing down the relaxation and degradation of their molecular junctions as hinokitiol is a hydrophobic compound with low permeability. Consequently, the degradation of hydrogel membranes with hinokitiol was delayed. In vitro cytocompatibility indicated that the cell viability of the groups with hinokitiol increased with incubation time, demonstrating that cell viability and proliferation were not affected by cell culture testing.

20.
BMC Infect Dis ; 19(1): 770, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481020

RESUMO

BACKGROUND: We sought to assess reporting in China's Pneumonia of Unknown Etiology (PUE) passive surveillance system for emerging respiratory infections and to identify ways to improve the PUE surveillance system's detection of respiratory infections of public health significance. METHODS: From February 29-May 29, 2016, we actively identified and enrolled patients in two hospitals with acute respiratory infections (ARI) that met all PUE case criteria. We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. We described and analyzed the proportion of PUE cases reported and clinician awareness of and practices related to the PUE system. RESULTS: Of 2619 ARI admissions in two hospitals, 335(13%) met the PUE case definition; none were reported. Of 311 specimens tested, 18(6%) were seasonal influenza virus-positive; none were avian influenza-positive. < 10% PUE case medical records documented whether or not there were exposures to animals or others with respiratory illness. Most commonly cited reasons for not reporting cases were no awareness of the PUE system (76%) and not understanding the case definition (53%). CONCLUSIONS: Most clinicians have limited awareness of and are not reporting to the PUE system. Exposures related to respiratory infections are rarely documented in medical records. Increasing clinicians' awareness of the PUE system and including relevant exposure items in standard medical records may increase reporting.


Assuntos
Notificação de Doenças , Necessidades e Demandas de Serviços de Saúde , Pneumonia/epidemiologia , Pneumonia/etiologia , Vigilância da População , Adulto , China/epidemiologia , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/epidemiologia , Diagnóstico Diferencial , Notificação de Doenças/métodos , Notificação de Doenças/normas , Feminino , Necessidades e Demandas de Serviços de Saúde/organização & administração , Necessidades e Demandas de Serviços de Saúde/normas , Hospitalização , Humanos , Influenza Humana/epidemiologia , Masculino , Notificação de Abuso , Testes Obrigatórios/normas , Pessoa de Meia-Idade , Projetos Piloto , Pneumonia/diagnóstico , Vigilância da População/métodos , Padrões de Prática Médica/organização & administração , Padrões de Prática Médica/normas , Avaliação de Programas e Projetos de Saúde , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Engajamento no Trabalho
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