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1.
BMC Anesthesiol ; 20(1): 2, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901229

RESUMO

BACKGROUND: As an essential component of multimodal analgesia approaches after total knee arthroplasty (TKA), local infiltration analgesia (LIA) can be classified into peri-articular injection (PAI) and intra-articular injection (IAI) according to administration techniques. Currently, there is no definite answer to the optimal choice between the two techniques. Our study aims to investigate analgesic efficacy and safety of PAI versus IAI in patients receiving simultaneous bilateral TKA. METHODS: This randomized controlled trial was conducted from February 2017 and finished in July 2018. Sixty patients eligible for simultaneous bilateral total knee arthroplasty were randomly assigned to receive PAI on one side and IAI on another. Primary outcomes included numerical rating scale (NRS) pain score at rest or during activity at 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h following surgery. Secondary outcomes contained active or passive range of motion (ROM) at 1, 2, and 3 days after surgery, time to perform straight leg raise, wound drainage, operation time, and wound complications. RESULTS: Patients experienced lower NRS pain scores of the knee receiving PAI compared with that with PAI during the first 48 h after surgery. The largest difference of NRS pain score at rest occurred at 48 h (PAI: 0.68, 95%CI[0.37, 0.98]; IAI: 2.63, 95%CI [2.16, 3.09]; P < 0.001); and the largest difference of NRS pain score during activity also took place at 48 h (PAI: 2.46, 95%CI [2.07, 2.85]; IAI: 3.90, 95%CI [3.27, 4.52]; P = 0.001). PAI group had better results of range of motion and time to perform straight leg raise when compared with IAI group. There were no differences in operation time, wound drainage, and wound complication. CONCLUSION: PAI had the superior performance of pain relief and improvement of range of motion to IAI. Therefore, the administration technique of peri-articular injection is recommended when performing local infiltration analgesia after total knee arthroplasty. TRIAL REGISTRATION: The trial was retrospectively registered in the Chinese Clinical Trial Registry as ChiCTR1800020420 on 29th December, 2018. LEVEL OF EVIDENCE: Therapeutic Level I.

2.
Theranostics ; 10(1): 74-90, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903107

RESUMO

Microglial activation participates in white matter injury after cerebral hypoperfusion. However, the underlying mechanism is unclear. Here, we explore whether activated microglia aggravate white matter injury via complement C3-C3aR pathway after chronic cerebral hypoperfusion. Methods: Adult male Sprague-Dawley rats (n = 80) underwent bilateral common carotid artery occlusion for 7, 14, and 28 days. Cerebral vessel density and blood flow were examined by synchrotron radiation angiography and three-dimensional arterial spin labeling. Neurobehavioral assessments, CLARITY imaging, and immunohistochemistry were performed to evaluate activation of microglia and C3-C3aR pathway. Furthermore, C3aR knockout mice were used to establish the causal relationship of C3-C3aR signaling on microglia activation and white matter injury after hypoperfusion. Results: Cerebral vessel density and blood flow were reduced after hypoperfusion (p<0.05). Spatial learning and memory deficits and white matter injury were shown (p<0.05). These impairments were correlated with aberrant microglia activation and an increase in the number of reactive microglia adhering to and phagocytosed myelin in the hypoperfusion group (p<0.05), which were accompanied by the up-regulation of complement C3 and its receptors C3aR (p<0.05). Genetic deletion of C3ar1 significantly inhibited aberrant microglial activation and reversed white matter injury after hypoperfusion (p<0.05). Furthermore, the C3aR antagonist SB290157 decreased the number of microglia adhering to myelin (p<0.05), attenuated white matter injury and cognitive deficits in chronic hypoperfusion rats (p<0.05). Conclusions: Our results demonstrated that aberrant activated microglia aggravate white matter injury via C3-C3aR pathway during chronic hypoperfusion. These findings indicate C3aR plays a critical role in mediating neuroinflammation and white matter injury through aberrant microglia activation, which provides a novel therapeutic target for the small vessel disease and vascular dementia.

3.
Theranostics ; 10(1): 265-280, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903119

RESUMO

We identified a novel long noncoding RNA (lncRNA) upregulated in colorectal cancer (CRC). We elucidated its role and clinical significance in CRC carcinogenesis. Methods: LncRNA candidates were identified using TCGA database. LncRNA expression profiles were studied by qRT-PCR and microarray in paired tumor and normal tissues. The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis. The mechanisms of lncRNA function and regulation in CRC were examined using molecular biological methods. Results: We identified a novel long noncoding gene (PiHL, P53 inHibiting LncRNA) from 8q24.21 as a p53 negative regulator. PiHL is drastically upregulated in CRC and is an independent predictor of CRC poor prognosis. Further in vitro and in vivo models demonstrated that PiHL was crucial in maintaining cell proliferation and inducing 5-FU chemoresistance through a p53-dependent manner. Mechanistically, PiHL acts to promote p53 ubiquitination by sequestering RPL11 from MDM2, through enhancing GRWD1 and RPL11 complex formation. We further show that p53 can directly bind to PiHL promoter and regulating its expression. Conclusion: Our study illustrates how cancer cells hijack the PiHL-p53 axis to promote CRC progression and chemoresistance. PiHL plays an oncogenic role in CRC carcinogenesis and is an independent prognostic factor as well as a potential therapeutic target for CRC patients.

4.
Trials ; 21(1): 19, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907024

RESUMO

BACKGROUND: Alzheimer's disease (AD) is an epidemic with tremendous public health impacts because there are currently no disease-modifying therapeutics. Randomized controlled trials (RCTs) for prevention of AD dementia often use clinical endpoints that take years to manifest (e.g., cognition) or surrogate endpoints that are costly or invasive (e.g., magnetic resonance imaging [MRI]). Blood biomarkers represent a clinically applicable alternative surrogate endpoint for RCTs that would be both cost-effective and minimally invasive, but little is known about their value as surrogate endpoints for treatment responses in the prevention of AD dementia. METHODS: The objective of this study is to investigate blood neuropathological, neurodegenerative, and neurotrophic biomarkers as surrogate endpoints for treatment responses to three interventions in older adults with amnestic mild cognitive impairment (aMCI, a prodromal stage of AD): aerobic exercise, cognitive training, and combined aerobic exercise and cognitive training (ACT). We chose these three sets of biomarkers for their unique mechanistic associations with AD pathology, neurodegeneration and neurogenesis. This study is built on the ACT Trial (1R01AG055469), a single-blinded, multi-site, 2 × 2 factorial phase II RCT that examines the synergistic effects of a 6-month ACT intervention on cognition and MRI biomarkers (AD-signature cortical thickness and hippocampal volume) (n = 128). In this ACT Trial blood biomarkers study, we will enroll 120 ACT Trial participants with aMCI and measure blood biomarkers at baseline and at 3, 6, 12, and 18 months. The goals are to (1) determine the effect of interventions on blood biomarkers over 6 months, (2) evaluate blood biomarkers as surrogate endpoints for predicting cognitive responses to interventions over 18 months, and (3, exploratory) examine blood biomarkers as surrogate endpoints for predicting brain MRI biomarker responses to interventions over 18 months. DISCUSSION: This study aims to identify new blood biomarkers that can track cognitive decline or AD-related brain atrophy among patients with aMCI subjected to a regimen of aerobic exercise and cognitive training. Findings from this study will drive the further use of blood biomarkers in developing effective prevention and treatment strategies for AD dementia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03313895. Registered on 18 October 2017.

5.
Phys Chem Chem Phys ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917380

RESUMO

Recently, fatty acid binding proteins 5 and 7 (FABP5 and FABP7) have been regarded as the prospective targets for clinically treating multiple diseases related to FABPs. In this work, multiple short molecular dynamics (MSMD) simulations followed by binding free energy calculations were performed to investigate the binding selectivity of three inhibitors, namely, 65X, 8KS, and 5M8 toward FABP5 and FABP7. The RMSF analysis suggests that the structural flexibility of FABP5 is stronger than that of FABP7; moreover, the calculated molecular surface area of FABP5 is also larger than that of FABP7. Meanwhile, the results from the cross-correlation analysis show that the inhibitor bindings exert different impacts on the internal dynamics of FABP5 and FABP7. Binding free energies predicted by the molecular mechanics/generalized Born surface area (MM-GBSA) method indicate that the increase in the enthalpy changes caused by the bindings of inhibitors toward FABP7 relative to FABP5 mostly drives the binding selectivity of the inhibitors toward FABP5 versus FABP7. Hierarchical clustering analysis based on the energy contributions of separate residues and calculations of residue-based free energy decompositions were carried out by using the equilibrated MSMD trajectories. The obtained results not only recognize the hot interaction spots of inhibitors with FABP5 and FABP7, but also display that several common residues, namely, (T56, T54), (L60, F58), (E75, E73), (A76, A78), (D79, D77), (R81, R79), (R107, R109), (C120, L118), and (R129, R127) belonging to (FABP5, FABP7) induce obvious binding differences in the inhibitors toward FABP5 and FABP7. Therefore, these residues play significant roles in the binding selectivities of inhibitors toward FABP5 and FABP7.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31900557

RESUMO

Lactic acid bacteria (LAB) are a unique subset of microorganisms that have co-evolved with humans since the beginning of agricultural practices and animal domestication and throughout our never-ending quest for food preservation, digestibility, and flavor enhancement. LAB have historically played a preponderant role in our foods. In this review, we focus on the enzymatic activities and current or potential applications of LAB in our lives. A description of each of the enzymatic systems in LAB is included. Glycosidases, which hydrolyze the most abundant food molecules and as sources of carbon, sustain the lives of organisms on Earth as well as ensure microbial innocuity by the production of lactic acid from the uniquely mammalian carbohydrate, lactose. Lipases and proteases or proteinases are of fundamental importance in food fermentations and in dairy foods for flavor development. Bacteriocins and peptidoglycan hydrolases are part of the enzymatic system of LAB that has evolved to make these bacteria fierce competitors in various microbiomes, which are highly important for the human gut. In this review, we also present an explanation on how the versatility of the genetics of LAB can adapt to the matrix where they are placed with the advantage of not having any toxicity to humans. The systematic study of LAB enzymes has allowed for some unique applications in foods and biopharmaceutical industries. Here, we summarize how different enzyme systems in LAB are classified, and thus, facilitate much-needed further studies to understand the fundamentals and translate them into applications to improve our lives.

7.
Science ; 367(6475): 272-277, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31949075

RESUMO

One great challenge in understanding the history of life is resolving the influence of environmental change on biodiversity. Simulated annealing and genetic algorithms were used to synthesize data from 11,000 marine fossil species, collected from more than 3000 stratigraphic sections, to generate a new Cambrian to Triassic biodiversity curve with an imputed temporal resolution of 26 ± 14.9 thousand years. This increased resolution clarifies the timing of known diversification and extinction events. Comparative analysis suggests that partial pressure of carbon dioxide (Pco2) is the only environmental factor that seems to display a secular pattern similar to that of biodiversity, but this similarity was not confirmed when autocorrelation within that time series was analyzed by detrending. These results demonstrate that fossil data can provide the temporal and taxonomic resolutions necessary to test (paleo)biological hypotheses at a level of detail approaching those of long-term ecological analyses.

8.
Carbohydr Polym ; 232: 115693, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952621

RESUMO

In order to improve the mechanical properties of alginate fiber and enrich its application properties, the metal-alginate fibers were produced with wet spinning in the coagulation bath of Zn2+, Ba2+, Cu2+, Al3+ ions blended with Ca2+ ions. FT-IR and 13C NMR were used to characterize the binding mode of alginic acid with metal ions and the arrangement of G and M groups in the molecular chain. The flame retardancy, mechanical and antibacterial properties of metal-alginate fiber were improved, while its water absorption was decreased. The results of Thermogravimetric (TG) and Limiting oxygen index (LOI) showed that the flame retardancy of metal-alginate fibers was better than that of calcium alginate fibers. The combination of metal ions and alginic acid has different improvement effect of mechanical strength and antimicrobial activity against Escherichia coli and Staphylococcus aureus. The multi-functional fiber is expected to be used in medical textiles and new textile fibers.

9.
Cancer Med ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953927

RESUMO

OBJECTIVE: Controversy still exists regarding the volume of radiation for head and neck cancer of unknown primary (HNCUP). Theoretically, elective mucosal irradiation (EMI) should achieve a balance between survival and toxicity. This prospective study was conducted to evaluate the long-term benefit of EMI in Chinese HNCUP patients. METHODS: A phase II, single-arm trial was performed at two centers in China. HNCUP patients with pathologically confirmed metastatic squamous cell carcinoma or poorly differentiated carcinoma were enrolled. Patients with metastatic lymph nodes limited to level IV and/or the supraclavicular fossa were excluded. The EMI approach was specifically customized to Chinese patients by differentiating HNCUP as putative nasopharyngeal carcinoma (NPC) or non-putative NPC. The primary endpoint was 3-year mucosal recurrence-free survival (MRFS). RESULTS: A total of 48 patients were enrolled between 02/02/2010 and 08/01/2018; 46 patients were analyzed, including 24 putative NPC and 22 non-putative NPC patients. No primary recurrence was observed during a median follow-up period of 70 months, and only 1 patient experienced out of field recurrence in the contralateral neck. The 3-year MRFS was 90.6% (95%CI: 76.4%-96.4%). The 5-year MRFS, regional-recurrence free survival (RRFS) and overall survival (OS) were 90.6% (95%CI: 76.4%-96.4%), 86.0% (95%CI: 71.1%-93.7%), and 90.6% (95%CI: 76.4%-96.4%), respectively. No grade 4 acute or late toxicities occurred, and the most frequent grade 3 acute toxicity was oral mucositis (45.7%). CONCLUSION: To the best of our knowledge, this is the first prospective study to evaluate the long-term outcomes of EMI in Chinese HNCUP patients. Excellent MRFS and OS rates were observed. Further randomized studies are warranted.

10.
Theranostics ; 10(3): 1136-1150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31938056

RESUMO

Development of small-sized nanoformulations for effective tumor penetration, particularly for those tumors with dense stroma is a major challenge in cancer nanomedicine. It is even more challenging to achieve effective co-loading of both hydrophobic and hydrophilic anticancer agents through a small-sized nanocarrier. In this work, we designed a novel redox-responsive gemcitabine (GEM)-conjugated polymer POEG-co-PVDGEM (PGEM) as a small-sized nanocarrier to co-deliver hydrophilic GEM and hydrophobic paclitaxel (PTX). Methods: The in vitro physicochemical and biological properties of PTX/PGEM NPs were characterized. The efficiency of the PGEM carrier in selective codelivery of GEM and PTX in two murine tumor models as well as a patient derived xenograft model (PDX) was also evaluated. In addition, we investigated the changes in tumor immune microenvironment after treatment with PTX/PGEM nanoparticles. Results: We discovered that GEM conjugation could significantly decrease the nanoparticle size from 160 nm to 13 nm. Moreover, different from most reported GEM-conjugated polymers, PGEM polymer could serve as a prodrug carrier to load a wide variety of hydrophobic agents with high drug loading capacity and excellent stability. More importantly, our strategy could be extended to various nucleotides-based drugs such as azacytidine, decitabine and cytarabine, suggesting a new platform for co-delivery of various first line hydrophilic and hydrophobic anticancer agents. Imaging showed that our small-sized carrier was much more effective in tumor accumulation and penetration compared to the relatively large-sized drug carrier. The PGEM prodrug-based carrier not only well retained the pharmacological activity of GEM, but also boosted T-cell immune response. Furthermore, delivery of PTX via PGEM led to significantly improved antitumor activity in several murine cancer models and a PDX model of colon cancer. Conclusion: This work not only provided a small-sized carrier platform that was able to load multiple hydrophilic and hydrophobic drugs with high loading capacity, but also provided an effective regimen for enhanced tumor penetration and improved anti-tumor immunity.

11.
Br J Nutr ; : 1-31, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31928547

RESUMO

The effect of holly polyphenols (HP) on intestinal inflammation and microbiota composition was evaluated in a piglet model of lipopolysaccharide (LPS)-induced intestinal injury. A total of 24 piglets were used in a 2 × 2 factorial design including diet type and LPS challenge. After 16 d of feeding with a basal diet supplemented with or without 250 mg/kg HP, pigs were challenged with LPS (100 µg/kg BW) or an equal volume of saline for 4 h, followed by analysis of disaccharidase activities, gene expression levels of several representative tight junction proteins and inflammatory mediators, the short-chain fatty acid (SCFA) concentrations, and microbiota composition in intestinal contents as well as proinflammatory cytokine levels in plasma. Our results indicated that HP enhanced intestinal disaccharidase activities and reduced plasma proinflammatory cytokines including tumor necrosis factor-α and interleukin-6 in LPS-challenged piglets. Moreover, HP upregulated mRNA expression of intestinal tight junction proteins such as claudin-1 and occludin. In addition, bacterial 16S rRNA gene sequencing showed that HP altered hindgut microbiota composition by enriching Prevotella and enhancing SCFA production following LPS challenge. These results collectively suggest that HP is capable of alleviating LPS-triggered intestinal injury by improving intestinal disaccharidase activities, barrier function, and SCFA production, while reducing intestinal inflammation.

12.
Small ; : e1905572, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943732

RESUMO

Cancer spheroids have structural, functional, and physiological similarities to the tumor, and have become a low-cost in vitro model to study the physiological responses of single cells and therapeutic efficacy of drugs. However, the tiny spheroid, made of a cluster of high-density cells, is highly scattering and absorptive, which prevents light microscopy techniques to reach the depth inside spheroids with high resolution. Here, a method is reported for super-resolution mapping of single nanoparticles inside a spheroid. It first takes advantage of the self-healing property of a "nondiffractive" doughnut-shaped Bessel beam from a 980 nm diode laser as the excitation, and further employs the nonlinear response of the 800 nm emission from upconversion nanoparticles, so that both excitation and emission at the near-infrared can experience minimal loss through the spheroid. These strategies lead to the development of a new nanoscopy modality with a resolution of 37 nm, 1/26th of the excitation wavelength. This method enables mapping of single nanoparticles located 55 µm inside a spheroid, with a resolution of 98 nm. It suggests a solution to track single nanoparticles and monitor their release of drugs in 3D multicellar environments.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31944101

RESUMO

The interfaces between 2D materials and silicon dioxide (SiO2)/silicon (Si) substrate, generally considered as a solid-solid mechanical contact, have been especially emphasized for the structure design and the property optimization in microsystems and nanoengineering. The basic understanding of interfacial structure and dynamics for 2D material-based systems still remains one of the inevitable challenges ahead. Here, an interfacial mobile water layer is indicated to insert into the interface of degraded black phosphorus (BP) flake and the SiO2/Si substrate owing to the induced hydroxyl groups during the ambient degradation. A super-slippery degraded BP/SiO2 interface was observed with the interfacial shear stress (ISS) experimentally evaluated as low as 0.029±0.004 MPa, being comparable to the ISS values of incommensurate rigid crystalline contacts. In-depth investigation of the interfacial structure through nuclear magnetic resonance spectroscopy and in-situ X-ray photoelectron spectroscopy depth profiling revealed that the interfacial liquid water was responsible for the super-slippery BP/SiO2 interface with extremely low shear stress. This finding clarifies the strong interactions between degraded BP and water molecules, which supports the potential wider applications of few-layer BP nanomaterial in biological lubrication.

14.
J Hazard Mater ; 387: 122015, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31927356

RESUMO

The ultra-low density AlCl3-chitosan composite aerogel was prepared via a novel solution-freeze-drying technology. Then, the AlCl3-chitosan aerogel was carbonized or calcined to remove the chitosan template, yielding ultra-low density Al2O3-based aerogels with good formation ability. The density of Al2O3-based aerogels were about 9 mg/cm3 via this method. Moreover, the Al2O3-based aerogel obtained from the calcination of AlCl3-chitosan aerogel copied the open networks of thin flakes layered structure of chitosan template. The as-prepared Al2O3 aerogel had a low thermal conductivity of about 0.039 W/m K after high temperature treatment at 1000 °C, demonstrating its good thermal insulation property. The results of TG/DSC showed that the Al2O3-(0.2 wt% Pt) catalysts could decrease decomposition temperature of ammonium perchlorate (AP) by 51.1 °C and the exothermic heat was increased from 133.2 J/g to 1552.7 J/g. The maximum adsorption amounts for U(VI) of Al2O3 aerogel reached 769.9 mg/g, which was about 2 times higher than that of Al2O3 with other forms. Accordingly, the Al2O3 aerogel with thin flakes layered structure and ultra-low density possessed great potential application in thermal insulation, adsorption and catalyst supports. Meanwhile, the solution-freeze-drying technology is simple and easy to control, providing a new strategy for the preparation of ultra-low density metal oxide aerogels.

15.
Int Immunopharmacol ; 80: 106156, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31945609

RESUMO

OBJECTIVE: Recently, the function of microRNAs (miRNAs) has been clarified in human diseases, we aimed to identify the role of miR-185 in myocardial infarction (MI). METHODS: Bone marrow mesenchymal stem cells (BMSCs) were cultured, from which the exosomes were extracted. MI mice models were established by coronary artery ligation and injected with transfected BMSCs. The echocardiographic and ventricle indicators, and hemodynamics of mice were measured. Moreover, the ultrastructure and apoptosis of cardiomyocytes were determined, and expression of miR-185, suppressor of cytokine signaling 2 (SOCS2), collagens, and apoptotic proteins in myocardial tissues were evaluated. RESULTS: MiR-185 was poorly expressed in myocardial tissues of MI mice. BMSCs-Exo could shuttle miR-185 to promote cardiac function and attenuate myocardial injury of myocardial tissues in MI mice, and also could protect cardiomyocytes from apoptosis in MI mice by reducing the expression of SOCS2. SOCS2 was determined to be the direct target gene of miR-185. Overexpressed SOCS2 could block the cardioprotective effect of BMSCs-derived exosomal miR-185 in MI mice. CONCLUSION: We have found in this study that BMSCs-derived exosomal miR-185 could repress ventricular remolding of MI mice by inhibiting SOCS2. This study may provide new method for MI treatment.

16.
Sci Total Environ ; 713: 136565, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31954244

RESUMO

The stereoselective effects of chiral ibuprofen (IBU) were studied using lipidomics by exposing adult zebrafish (Danio rerio) to an environmental concentration of 5 µg/L for 28 days. After treatment with rac-/R-(-)-/S-(+)-IBU, the brain tissue of the zebrafish was harvested to analyze for lipid metabolites by using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Results showed that the six classes of lipids, namely, glycerophospholipids, sterol lipids, prenol lipids, fatty acyls, glycerolipids, and sphingolipids, including 46 biomarkers, were affected after exposure. The different influences on metabolites were observed in the rac-/R-(-)-/S-(+)-IBU-treated samples. The rac-IBU treatment remarkably affected nine lipids. The R-(-)-IBU and S-(+)-IBU treatments had remarkably effects on six and four lipids, respectively. According to the HMDB database and KEGG pathways, nine important lipids were successfully matched to the involved biochemical pathways, such as glycerophospholipid metabolism, arachidonic acid metabolism, and linoleic acid metabolism. Therefore, IBU can cause disorders in the metabolism of the brain lipids of adult zebrafish and affect the composition of biological membranes, inflammatory responses, and cardiovascular and cerebrovascular diseases. The significant difference in the effects of R-(-)-IBU and S-(+)-IBU on lipidomics indicated that chiral IBU has stereoselective toxicity to aquatic organisms. Our study provided new insights into the environmental toxicology and highlighted the hazard of pharmaceutical and personal care product pollution in aquatic environments.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31956954

RESUMO

PURPOSE: Compact master manipulators have inherent advantages, since they can have practical deployment within the general surgical environments easily and bring benefits to surgical training. To assess the advantages of compact master manipulators for surgical skills training and the performance of general robot-assisted surgical tasks, Hamlyn Compact Robotic Master (Hamlyn CRM) is built up and evaluated in this paper. METHODS: A compact structure for the master manipulator is proposed. A novel sensing system is designed while stable real-time motion tracking can be realized by fusing the information from multiple sensors. User studies were conducted based on a ring transfer task and a needle passing task to explore a suitable mapping strategy for the compact master manipulator to control a surgical robot remotely. The overall usability of the Hamlyn CRM is verified based on the da Vinci Research Kit (dVRK). The master manipulators of the dVRK control console are used as the reference RESULTS: Motion tracking experiments verified that the proposed system can track the operators' hand motion precisely. As for the master-slave mapping strategy, user studies proved that the combination of the position relative mapping mode and the orientation absolute mapping mode is suitable for Robot-Assisted Minimally Invasive Surgery (RAMIS), while key parameters for mapping are selected. CONCLUSION: Results indicated that the Hamlyn CRM can serve as a compact master manipulator for surgical training and has potential applications for RAMIS.

18.
Circulation ; 141(1): 42-66, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31887080

RESUMO

BACKGROUND: Sporadic aortic aneurysm and dissection (AAD), caused by progressive aortic smooth muscle cell (SMC) loss and extracellular matrix degradation, is a highly lethal condition. Identifying mechanisms that drive aortic degeneration is a crucial step in developing an effective pharmacologic treatment to prevent disease progression. Recent evidence has indicated that cytosolic DNA and abnormal activation of the cytosolic DNA sensing adaptor STING (stimulator of interferon genes) play a critical role in vascular inflammation and destruction. Here, we examined the involvement of this mechanism in aortic degeneration and sporadic AAD formation. METHODS: The presence of cytosolic DNA in aortic cells and activation of the STING pathway were examined in aortic tissues from patients with sporadic ascending thoracic AAD. The role of STING in AAD development was evaluated in Sting-deficient (Stinggt/gt) mice in a sporadic AAD model induced by challenging mice with a combination of a high-fat diet and angiotensin II. We also examined the direct effects of STING on SMC death and macrophage activation in vitro. RESULTS: In human sporadic AAD tissues, we observed the presence of cytosolic DNA in SMCs and macrophages and significant activation of the STING pathway. In the sporadic AAD model, Stinggt/gt mice showed significant reductions in challenge-induced aortic enlargement, dissection, and rupture in both the thoracic and abdominal aortic regions. Single-cell transcriptome analysis revealed that aortic challenge in wild-type mice induced the DNA damage response, the inflammatory response, dedifferentiation and cell death in SMCs, and matrix metalloproteinase expression in macrophages. These changes were attenuated in challenged Stinggt/gt mice. Mechanistically, nuclear and mitochondrial DNA damage in SMCs and the subsequent leak of DNA to the cytosol activated STING signaling, which induced cell death through apoptosis and necroptosis. In addition, DNA from damaged SMCs was engulfed by macrophages in which it activated STING and its target interferon regulatory factor 3, which directly induced matrix metalloproteinase-9 expression. We also found that pharmacologically inhibiting STING activation partially prevented AAD development. CONCLUSIONS: Our findings indicate that the presence of cytosolic DNA and subsequent activation of cytosolic DNA sensing adaptor STING signaling represent a key mechanism in aortic degeneration and that targeting STING may prevent sporadic AAD development.

19.
Eur J Pharmacol ; 868: 172874, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31866410

RESUMO

Airway remodeling in asthma is difficult to treat because of its complex pathophysiology that involves proinflammatory cytokines, as well as the arachidonic acid cytochrome P-450 (CYP) pathway; however, it has received little attention. In this study, we assessed the efficacy of a soluble epoxide hydrolase (sEH) on airway remodeling in a mouse model of chronic asthma. The expression of sEH and CYP2J2 and the level of 14,15-epoxyeicosatrienoic acid (14,15-EET), airway remodeling and hyperresponsiveness (AHR) were analyzed to determine the level of sEH inhibition. AUDA, a sEH inhibitor, was given daily for 9 weeks orally, which significantly increased the level of 14,15-EET by inhibiting the expression of sEH and increasing the expression of CYP2J2 in lung tissues. The inhibition of sEH reduced the expression of remodeling-related molecular markers, such as interleukin (IL)-13, IL-17, matrix metalloproteinase 9, N-cadherin, α-smooth muscle actin (α-SMA), S100A4, Twist, epithelial goblet cell metaplasia, and collagen deposition in bronchoalveolar lavage fluid (BAL fluid) and lung tissues. Moreover, remodeling-related eosinophil accumulation in the BAL fluid and infiltration into the lung tissue were improved by AUDA. Finally, AUDA alleviated AHR, which is a functional indicator of airway remodeling. The effect of AUDA on airway remodeling was related to the downregulation of extracellular-regulated protein kinases (Erk1/2), c-Jun N-terminal kinases (JNK) and signal transducer and activator of transcription 3 (STAT3). To our knowledge, this is the first report to demonstrate that inhibition of sEH exerts significant protective effects on airway remodeling in asthma.

20.
Genet Test Mol Biomarkers ; 23(12): 829-836, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31821092

RESUMO

Background: Pancreatic adenocarcinoma (PAAD) is an aggressive and invasive tumor with poor prognosis. Identifying prognostic biomarkers of PAAD will provide crucial information for developing treatment plans. Methods: In this analysis, a gene-expression dataset, containing RNA-sequencing data recalculated into transcripts per million, was obtained from the UCSC Xena platform. Three thousand nine hundred and seventy six differentially expressed genes were obtained with analysis of variance. Using these data a co-expression network was constructed using weighted gene co-expression network analysis, from which we obtained eight modules. Results: The blue module included 497 genes and demonstrated significant negative correlation with overall survival. Furthermore, pathway analyses demonstrated the involvement of many of these genes in the tight junction pathway, which plays a critical role in PAAD. In addition, we identified six genes in common (i.e., ANXA2 [annexin A2], EPHA2 [erythropoietin-producing hepatocellular class A2], ITGB4 [integrin beta 4], KRT19 [keratin type I cytoskeletal 19], LGALS3 [galectin-3], and S100A14 [S100 calcium binding protein A14]) between the protein-protein interaction and gene co-expression networks that may have critical functions in PAAD. These hub genes were not only highly expressed at the RNA level but also exhibited high expression in the immunohistological data in the Human Protein Atlas Database. Conclusion: Thus, this research clarified the framework of co-expressed gene modules in PAAD and highlighted potential prognostic biomarkers for the clinical diagnosis of PAAD.

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