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1.
Artigo em Inglês | MEDLINE | ID: mdl-31486708

RESUMO

Purpose: To compare the results of two- versus three-staged laparoscopic anorectoplasty (LARP) in children with rectoprostatic and bladder neck fistulas. Materials and Methods: The present study was retrospectively initiated among 32 consecutive patients who underwent two-staged LARP from October 2010 to December 2012. The associated defects, age at the operation, operative time, complications, length of the postoperative hospital stay, total hospitalization cost, and functional results (according to the Krickenbeck scoring system) were evaluated. The results were compared with those of 19 cases who underwent three-staged LARP from October 2008 to September 2010. Results: The average age at the second operation was 4.5 ± 1.2 months in the two-staged group, and 4.2 ± 1.3 months in the three-staged group. In the two-staged group, there were statistically shorter overall operative time and postoperative hospital stay duration. Also, a significantly lower total hospitalization cost was achieved. There was no anastomotic leak in either group. The rates of perineal wound infection, recurrent fistula, and rectal prolapse were 3.85% versus 0% (P = 1.000), 0% versus 5.3% (P = .422), and 11.5% versus 15.8% (P = .686), respectively (two-staged versus three-staged group). The median follow-up time was 67 (range, 54-80) months and 88 (range, 81-104) months, respectively. No significant difference in functional outcome was observed. Conclusions: Two-staged LARP is feasible, safe, and more cost-effective, with comparable incidences of complications and functional outcomes with respect to a three-staged procedure.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31482718

RESUMO

We reported a novel HIV-1 circulating recombinant form among three epidemiologically unlinked patients through men having sex with men (MSM) in Hebei Province, China. It was named CRF103_01B (this is temporary as we have not received the CRF number from HIV databases). A near full-length genome (NFLG) phylogenetic tree showed that CRF103_01B was generated by three B (Western origin) segments and CRF01_AE that was described as cluster 5 lineage of CRF01_AE (CRF01-5). The emergence of CRF103_01B increased the complexity of the HIV-1 epidemic in China.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31482723

RESUMO

In this study, we report a novel HIV-1 second-generation recombinant form composed of CRF01_AE and subtype B detected from a married HIV-positive male subject infected through homosexual behavior in Tianjin in northern China. The near full-length genome (NFLG) analyses showed that two regions of subtype B inserted into the CRF01_AE backbone with four recombinant breakpoints observed in the pol gene region. Subregion tree analyses demonstrated that the CRF01_AE regions of the recombinant were greatly clustered with the CRF01_AE sub-cluster 4 lineage, which was found primarily among men who have sex with men (MSM) in northern China. To the best of our knowledge, this is the first detection of a novel HIV-1 second-generation recombinant form (CRF01AE/B) in Tianjin, which indicates active transmission networks of HIV-1 infection among MSM in this region. The emergence of the novel second-generation recombinant form highlights the increasing complexity of HIV-1 epidemic among MSM population and the importance to monitor potential novel circulating recombinant forms (CRFs).

4.
Artigo em Inglês | MEDLINE | ID: mdl-31482724

RESUMO

Recently, more and more kinds of circulating forms (CRFs) and unique recombinant forms (URFs) identified in the population in China. A novel HIV-1 recombinant virus (2016GXNNIDU016) was identified in this study, which was isolated from an HIV-1 infected intravenous drug user in Nanning, the capital of Guangxi, China. Phylogenetic analysis of the near full-length genome (NFLG) indicated that the sequence (2016GXNNIDU016) was a monophyletic branch that did not cluster with any previously identified genotype. Recombinant analysis showed that the NFLG of 2016GXNNIDU016 is composed of CRF07_BC, CRF01_AE and CRF08_BC, including nine mosaic segments. Differing from previously documented CRF01_AE and CRF07/08_BC recombinant forms, 2016GXNNIDU016 increases the genetic complexity of HIV-1 in Guangxi. The constant emergence of novel recombinant forms should draw our attention to make more efforts in supervising and preventing the spread of HIV infection.

6.
Nanotechnology ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509803

RESUMO

Ultralow-temperature sintering plays a vital role in the development of flexible printed electronics, which improves flexibility and reduces energy consumption. This study investigates the ultralow-temperature sintering of large-sized silver nanoparticles (Ag NPs) by laser modification of the substrate surface. Ag NPs in conductive ink were sintered at only 60 °C. Designing the appropriate size of modified regions, the sintered Ag layer exhibits a sheet resistance of only 0.274 Ω and withstands 10,000 folding cycles. Energy-dispersive X-ray spectroscopy showed that TiO2 formed by laser ablation promotes the sintering of Ag NPs and joining with the substrate. A paper-based flexible integrated circuit board was also prepared.

7.
IEEE Trans Cybern ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31478881

RESUMO

Due to uncertainty and dynamic characteristics from intermittent energy and load demand response (DR), the optimal operation of the hybrid energy system is a great challenge. This article proposes an event-triggered multiagent coordinated optimization strategy with two-layered architecture. First, the price-bidding-based DR model is proposed with different stakeholders, and it also deduces the optimal bidding price with the Nash equilibrium theory. Then, four agents are designed to control different kinds of energy resources: agent 1 mainly analyzes the uncertainty or randomness caused by intermittent power, agent 2 takes charge of the dynamic economic dispatch (DED) within thermal units, agent 3 manages the optimal scheduling of energy storage, and agent 4 mainly undertakes the load-shifting strategy from consumers. In the upper-layer level, all agents coordinate together to ensure the stability of the hybrid energy system with an event-triggered mechanism, and the intelligent control approach mainly depends on switching on/off power generators or curtailing system load, and the consensus algorithm is utilized to optimize the subsystem problem in the lower-layer level. Furthermore, the simulation results can further verify the efficiency of the proposed method, and it also reveals that the event-triggered multiagent optimization strategy can be a promising way to solve the hybrid energy system problem.

8.
J Vis Exp ; (150)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31475974

RESUMO

The discovery and development of immuno-oncology (I-O) therapy in recent years represents a milestone in the treatment of cancer. However, treatment challenges persist. Robust and disease-relevant animal models are vital resources for continued preclinical research and development in order to address a range of additional immune checkpoints. Here, we describe a human peripheral blood mononuclear cell (PBMC) - based humanized xenograft model. BGB-A317 (Tislelizumab), an investigational humanized anti-PD-1 antibody in late-stage clinical development, is used as an example to discuss platform set-up, model characterization and drug efficacy evaluations. These humanized mice support the growth of most human tumors tested, thus allowing the assessment of I-O therapies in the context of both human immunity and human cancers. Once established, our model is comparatively time- and cost-effective, and usually yield highly reproducible results. We suggest that the protocol outlined in this article could serve as a general guideline for establishing mouse models reconstituted with human PBMC and tumors for I-O research.

9.
Connect Tissue Res ; : 1-10, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429324

RESUMO

Intervertebral disc degeneration-related diseases are common health problems in the department of orthopedics. However, there is no effective treatment protecting the intervertebral disc from degeneration. Sesamin, a kind of sesame lignans extracted from sesame seed oil, has been proved to inhibit lipopolysaccharide-induced inflammation and extracellular matrix catabolism in rat intervertebral disc in vitro and ex vivo. The present study was designed to investigate the effects of sesamin on lesion-induced intervertebral disc degeneration in vivo. Degeneration of rat tail disc was induced by puncture lesion, followed by intradiscal injection of sesamin. Magnetic resonance imaging (MRI), quantitative real-time polymerase chain reaction, histological analysis, and biochemical analysis were carried out to analyze degeneration progression 2 weeks after surgery. As shown by results, intradiscal injection of sesamin inhibited the MRI signal decrease of nucleus pulposus (NP) in T2-weighted images. The upregulated mRNA expression of MMP-3 and ADAMTS-5 induced by lesion was significantly suppressed by sesamin injection. Sesamin partly protected mRNA expression of Col2a1 and Acan from downregulation. Intradiscal injection of sesamin effectively maintained the normal morphology of disc and inhibited lesion-induced degeneration-related histological changes. Immunohistochemical assay demonstrated that the upregulation of degradative enzymes protein expression and the downregulation of type II collagen expression in NP were suppressed by sesamin. According to biochemical analysis, sesamin significantly inhibited the lesion-induced decrease of proteoglycan content in NP. The present study proved the protective effects of sesamin on lesion-induced intervertebral disc degeneration at an early stage.

10.
Nature ; 573(7772): 96-101, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31462779

RESUMO

The viscoelasticity of the crosslinked semiflexible polymer networks-such as the internal cytoskeleton and the extracellular matrix-that provide shape and mechanical resistance against deformation is assumed to dominate tissue mechanics. However, the mechanical responses of soft tissues and semiflexible polymer gels differ in many respects. Tissues stiffen in compression but not in extension1-5, whereas semiflexible polymer networks soften in compression and stiffen in extension6,7. In shear deformation, semiflexible polymer gels stiffen with increasing strain, but tissues do not1-8. Here we use multiple experimental systems and a theoretical model to show that a combination of nonlinear polymer network elasticity and particle (cell) inclusions is essential to mimic tissue mechanics that cannot be reproduced by either biopolymer networks or colloidal particle systems alone. Tissue rheology emerges from an interplay between strain-stiffening polymer networks and volume-conserving cells within them. Polymer networks that soften in compression but stiffen in extension can be converted to materials that stiffen in compression but not in extension by including within the network either cells or inert particles to restrict the relaxation modes of the fibrous networks that surround them. Particle inclusions also suppress stiffening in shear deformation; when the particle volume fraction is low, they have little effect on the elasticity of the polymer networks. However, as the particles become more closely packed, the material switches from compression softening to compression stiffening. The emergence of an elastic response in these composite materials has implications for how tissue stiffness is altered in disease and can lead to cellular dysfunction9-11. Additionally, the findings could be used in the design of biomaterials with physiologically relevant mechanical properties.

11.
Chin J Integr Med ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31418133

RESUMO

OBJECTIVE: To investigate a Met-controlled allosteric module (AM) of neural generation as a potential therapeutic target for brain ischemia. METHODS: We selected Markov clustering algorithm (MCL) to mine functional modules in the related target networks. According to the topological similarity, one functional module was predicted in the modules of baicalin (BA), jasminoidin (JA), cholic acid (CA), compared with I/R model modules. This functional module included three genes: Inppl1, Met and Dapk3 (IMD). By gene ontology enrichment analysis, biological process related to this functional module was obtained. This functional module participated in generation of neurons. Western blotting was applied to present the compound-dependent regulation of IMD. Co-immunoprecipitation was used to reveal the relationship among the three members. We used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion group. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were supposed to show the changing circumstances for neural generation under cerebral ischemia. RESULTS: Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group (P<0.05). Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory activities. An anti-ischemic excitatory allosteric module (AME) of generation of neurons (AME-GN) was validated successfully in vivo. Newborn neurons increased in BJC treatment group (P<0.05). The expression of VEGF and MMP-9 decreased in the compound treatment groups compared with the I/R model group (P<0.05). CONCLUSIONS: AME demonstrates effectiveness of our pioneering approach to the discovery of therapeutic target. The novel approach for AM discovery in an effort to identify therapeutic targets holds the promise of accelerating elucidation of underlying pharmacological mechanisms in cerebral ischemia.

12.
Mol Immunol ; 114: 251-259, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31398664

RESUMO

BACKGROUND: Fracture healing is a complex process, and patients with fracture will undergo non-union or compromised regeneration. MicroRNA (miR)-342-5p is a Notch downstream molecule, and its roles in fracture healing remain unclear. We aimed to explore the functional roles of miR-342-5p in osteoblasts as well as the underlying mechanisms. METHODS: The expression of miR-342-5p in differentiation of MC3T3-E1 cells or hMSCs was examined by quantitative reverse transcription PCR (qRT-PCR). The effects of aberrantly expressed miR-342-5p on cell proliferation, apoptosis, migration, and expressions of proteins associated with proliferation and osteogenic differentiation were determined by Cell Counting Kit-8, trypan blue staining, flow cytometry, Transwell assay, Western blot and qRT-PCR assays, respectively. The downstream factor and the target genes of miR-342-5p as well as the involvements of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway were finally assessed. RESULTS: miR-342-5p level was decreased during differentiation of MC3T3-E1 cells or hMSCs. After cell transfection, miR-342-5p overexpression significantly reduced cell viability, induced apoptosis, inhibited proliferation, migration and differentiation, and down-regulated Bmp7 expression. Subsequent experiments showed the effects of miR-342-5p inhibition on MC3T3-E1 cells were abrogated by Bmp7 knockdown. Additionally, COL4A6 and Bmp2 were predicated as target genes of miR-342-5p. Finally, phosphorylated levels of MEK and ERK were increased by miR-342-5p inhibition via up-regulating Bmp7 expression. CONCLUSION: miR-342-5p inhibition promoted proliferation, migration and differentiation of osteoblasts via regulating Bmp7, along with activation of the MEK/ERK pathway.

13.
Food Chem Toxicol ; 133: 110781, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31465820

RESUMO

The aim of the present study was to explore the protective effects of raspberry and its bioactive compound cyanidin 3-O-glucoside against H2O2-induced oxidative stress in HepG2 cells. We established a model of oxidative stress in HepG2 cells induced by H2O2 and examined the protein expression of Keap1/Nrf2. The antioxidant activity of raspberry extract was carried out measuring the level of reactive oxygen species (ROS), and the changes of phase II detoxification elements such as GSH level and CAT activity. Also the expression of proteins related to the Keap1/Nrf2 signaling was tested. The results revealed that raspberry extract significantly reduced the ROS levels in oxidative injured cells, increased GSH content and CAT activity, and activated the expression of proteins Keap1, Nrf2, HO-1, NQO1, and γ-GCS. These results taken together indicated that raspberry treatment could ameliorate H2O2-induced oxidative stress in HepG2 cells via Keap1/Nrf2 pathway.

14.
Int Immunopharmacol ; 74: 105724, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31272064

RESUMO

The effect of Fusobacterium nucleatum (F. nucleatum) autoinducer-2 (AI-2) on the polarization of macrophages and the underlying mechanism is not known. We investigated the effect of F. nucleatum AI-2 on the migration and polarization of cultured macrophages. We further screened AI-2-interacting proteins in macrophages using a quantitative proteomics strategy, and evaluated the expression of TNFSF9/TRAF1/p-AKT/IL-1ß signaling in cultured macrophages and human colorectal cancer (CRC). The data showed that F. nucleatum AI-2 enhanced the mobility and M1 polarization of macrophages, possibly through TNFSF9/TRAF1/p-AKT/IL-1ß signaling. Moreover, TNFSF9 and IL-1ß expression was significantly increased in human CRCs when compared to normal colon (P < 0.05), and was associated with AI-2 concentration and increased survival. Together, our data suggested that AI-2 induced macrophage M1 polarization by activating the TNFSF9/IL-1ß pathway. Thus, AI-2 may serve as a promising novel target for immunotherapy of gut microbiota-related diseases.

15.
J Immunol ; 203(5): 1172-1188, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350356

RESUMO

T cells suddenly appeared in jawed fish ∼450 million years ago. Biological studies of fish T cells may provide helpful evidence to understand evolution of adaptive immune systems. To this end, using a Nile tilapia (Oreochromis niloticus) model, we revealed the regulatory mechanism of adaptive immunity mediated by ancestral T cells in jawed fish. Nile tilapia T cells as well as a tightly regulated mammalian/mechanistic target of rapamycin complex 1 (mTORC1) pathway participate in the cellular adaptive immune response during Streptococcus agalactiae infection. Blockade of mTORC1 signaling by rapamycin impairs T cell activation and Ag-induced proliferation in this early vertebrate. More critically, we show that signals from mTORC1 are indispensable for primordial effector T cells to eliminate infection by promoting the expression of proinflammatory cytokines, cytotoxic-related molecules, and proapoptotic genes. Mechanistically, teleost mTORC1 directs effector T cell function by coordinating multiple metabolic programs, including glycolysis, glutaminolysis, and lipogenesis through activating key transcription factors c-Myc, HIF-1α, and sterol regulatory element-binding proteins, and thus links immune signals to metabolic reprogramming in jawed fish. To our knowledge, these results represent the first description of the regulatory mechanism for T cell-mediated adaptive immunity in a fish species. From an evolutionary viewpoint, our study suggests that primordial T cells are armed with sophisticated regulatory strategies like those in modern T cells prior to the divergence of bony fish from the tetrapod lineage. Therefore, our findings fill in an important gap regarding evolution of the adaptive immune system.

16.
Plant J ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31355982

RESUMO

Plants are considered an important food and nutrition source for humans. Despite advances in plant seed metabolomics, knowledge about the genetic and molecular bases of rice seed metabolomes at different developmental stages is still limited. Here, using Zhenshan 97 (ZS97) and Minghui 63 (MH63), we performed a widely targeted metabolic profiling in seeds during grain filling, mature seeds and germinating seeds. The diversity between MH63 and ZS97 was characterized in terms of the content of metabolites and the metabolic shifting across developmental stages. Taking advantage of the ultra-high-density genetic map of a population of 210 recombinant inbred lines (RILs) derived from a cross between ZS97 and MH63, we identified 4681 putative metabolic quantitative trait loci (mQTLs) in seeds across the three stages. Further analysis of the mQTLs for the codetected metabolites across the three stages revealed that the genetic regulation of metabolite accumulation was closely related to developmental stage. Using in silico analyses, we characterized 35 candidate genes responsible for 30 structurally identified or annotated compounds, among which LOC_Os07g04970 and LOC_Os06g03990 were identified to be responsible for feruloylserotonin and l-asparagine content variation across populations, respectively. Metabolite-agronomic trait association and colocation between mQTLs and phenotypic quantitative trait loci (pQTLs) revealed the complexity of the metabolite-agronomic trait relationship and the corresponding genetic basis.

17.
J Org Chem ; 84(16): 10024-10031, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31283876

RESUMO

Retro-Brook rearrangements refer to the intramolecular migration of a silyl group from oxygen to carbon. In this study, we report a novel propargylic retro-Brook rearrangement observed in terminal alkynes bearing a silyl ether moiety. Retro-Brook rearrangements involving [1,2]-, [1,4]-, and [1,5]-migrations are described, affording propargylsilanes in reasonable yield. The reaction mechanism was investigated experimentally by deuterium quenching and rationalized by density functional theory calculations. The terminal alkyne and the subsequent propargyl/allenyl dianion were shown to be crucial for the reaction favoring the retro-Brook rearrangement product over the Brook rearrangement. The second deprotonation at the propargylic position was determined to be the rate-limiting step. In addition, a gas-phase Brook-type rearrangement of the propargylsilanes was observed under GC-MS conditions. This observation was also further confirmed by DFT calculations.

18.
Anal Chim Acta ; 1078: 119-124, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31358209

RESUMO

In this work, CaF2 nanoparticles were successfully synthesized by a simple direct precipitation method and firstly used as a peroxidase mimics for rapid and high sensitive colorimetric detection of aldosterone. The CaF2 nanoparticles were characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM) and powder X-ray diffraction (XRD). The CaF2 nanoparticles can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue product oxidized TMB (oxTMB) in the presence of H2O2 and this peroxidase-like activity of CaF2 is found out to follow Michaelis-Menten kinetics. Experiments showed that the catalytic mechanism of CaF2 nanoparticles was attributed to that it could result in the decomposition of H2O2 to produce hydroxyl radicals (•OH). The absorbance change value of the reaction system was linear with the aldosterone concentration in the range of 2.0-40.0 nM, and the detection limit was 0.6 nM. Moreover, the developed method was applied to detect aldosterone in human serum samples. It provides a new platform for enzyme functional simulation and analytical sensing research.

19.
J Cell Biochem ; 120(11): 18659-18666, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31347734

RESUMO

OBJECTIVE: We sought to identify novel molecular subtypes of high-grade serous ovarian cancer (HGSC) by the integration of gene expression and proteomics data and to find the underlying biological characteristics of ovarian cancer to improve the clinical outcome. METHODS: The iCluster method was utilized to analysis 131 common HGSC samples between TCGA and Clinical Proteomic Tumor Analysis Consortium databases. Kaplan-Meier survival curves were used to estimate the overall survival of patients, and the differences in survival curves were assessed using the log-rank test. RESULTS: Two novel ovarian cancer subtypes with different overall survival (P = .00114) and different platinum status (P = .0061) were identified. Eighteen messenger RNAs and 38 proteins were selected as differential molecules between subtypes. Pathway analysis demonstrated arrhythmogenic right ventricular cardiomyopathy pathway played a critical role in the discrimination of these two subtypes and desmosomal cadherin DSG2, DSP, JUP, and PKP2 in this pathway were overexpression in subtype I compared with subtype II. CONCLUSION: Our study extended the underlying prognosis-related biological characteristics of high-grade serous ovarian cancer. Enrichment of desmosomal cadherin increased the risk for HGSC prognosis among platinum-sensitive patients, the results guided the revision of the treatment options for platinum-sensitive ovarian cancer patients to improve outcomes.

20.
Chemistry ; 25(51): 11903-11909, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31274212

RESUMO

Molecular or supramolecular level photoluminescence (PL) modulation combining chemical and photonic input/output signals together in an integrated system can provide potential high-density data memorizing and process functions intended for miniaturized devices and machines. Herein, a PL-responsive supramolecular coordination cage has been demonstrated for complex interactions with redox-active guests. PL signals of the cage can be switched and modulated by adding or retracting Fc derivatives or converting TTF into different oxidation states through chemical or photochemical pathways. As a result, reversible or stepwise PL responses are displayed by these host-guest systems because of the occurrence of photoinduced electron-transfer (PET) or fluorescence resonance energy transfer (FREnT) processes, providing unique nanodevice models bearing off/on logic gates or memristor-like sequential memory and Boolean operation functions.

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