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1.
Immunity ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31471107

RESUMO

Although recent progress provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), rare anti-PF therapeutics show definitive promise for treating this disease. Repeated lung epithelial injury results in injury-repairing response and inflammation, which drive the development of PF. Here, we report that chronic lung injury inactivated the ubiquitin-editing enzyme A20, causing progressive accumulation of the transcription factor C/EBPß in alveolar macrophages (AMs) from PF patients and mice, which upregulated a number of immunosuppressive and profibrotic factors promoting PF development. In response to chronic lung injury, elevated glycogen synthase kinase-3ß (GSK-3ß) interacted with and phosphorylated A20 to suppress C/EBPß degradation. Ectopic expression of A20 or pharmacological restoration of A20 activity by disturbing the A20-GSK-3ß interaction accelerated C/EBPß degradation and showed potent therapeutic efficacy against experimental PF. Our study indicates that a regulatory mechanism of the GSK-3ß-A20-C/EBPß axis in AMs may be a potential target for treating PF and fibroproliferative lung diseases.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31471691

RESUMO

Matriptase is a type II transmembrane serine protease, which has been suggested to play critical roles in numerous pathways of biological developments. Matriptase is the activator of several oncogenic proteins, including urokinase-type plasminogen activator (uPA), hepatocyte growth factor (HGF) and protease-activated receptor 2 (PAR-2). The activations of these matriptase substrates subsequently lead to the generation of plasmin, matrix metalloproteases (MMPs), and the triggers for many other signaling pathways related to cancer proliferation and metastasis. Accordingly, matriptase is considered an emerging target for the treatments of cancer. Thus far, inhibitors of matriptase have been developed as potential anti-cancer agents, which include small-molecule inhibitors, peptide-based inhibitors, and monoclonal antibodies. This review covers established literature to summarize the chemical and biochemical aspects, especially the inhibitory mechanisms and structure-activity relationships (SARs) of matriptase inhibitors with the goal of proposing the strategies for their future developments in anti-cancer therapy.

3.
Phys Rev Lett ; 123(7): 073001, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31491105

RESUMO

We generate high-fidelity massively entangled states in an antiferromagnetic spin-1 Bose-Einstein condensate (BEC) by utilizing multilevel oscillations. Combining the multilevel oscillations with additional adiabatic drives, we greatly shorten the necessary evolution time and relax the requirement on the control accuracy of quadratic Zeeman splitting, from microgauss to milligauss, for a ^{23}Na spinor BEC. The achieved high fidelities over 96% show that two kinds of massively entangled states, the many-body singlet state and the twin-Fock state, are almost perfectly generated. The generalized spin squeezing parameter drops to a value far below the standard quantum limit even with the presence of atom number fluctuations and stray magnetic fields, illustrating the robustness of our protocol under real experimental conditions. The generated many-body entangled states can be employed to achieve the Heisenberg-limit quantum precision measurement and to attack nonclassical problems in quantum information science.

4.
Viruses ; 11(9)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487941

RESUMO

Adenoviral viral vectors have been widely used for gene-based therapeutics, but commonly used serotype 5 shows poor transduction efficiency into hematopoietic cells. In this study, we aimed to generate a recombinant adenovirus serotype 5 (rAd5) vector that has a high efficiency in gene transfer to megakaryocytic leukemic cells with anticancer potential. We first modified the rAd5 backbone vector with a chimeric fiber gene of Ad5 and Ad11p (rAd5F11p) to increase the gene delivery efficiency. Then, the nonstructural protein NS1 of human parvovirus B19 (B19V), which induces cell cycle arrest at the G2/M phase and apoptosis, was cloned into the adenoviral shuttle vector. As the expression of parvoviral NS1 protein inhibited Ad replication and production, we engineered the cytomegalovirus (CMV) promoter, which governs NS1 expression, with two tetracycline operator elements (TetO2). Transfection of the rAd5F11p proviral vectors in Tet repressor-expressing T-REx-293 cells produced rAd in a large quantity. We further evaluated this chimeric rAd5F11p vector in gene delivery in human leukemic cells, UT7/Epo-S1. Strikingly, the novel rAd5F11p-B19NS1-GFP vector, exhibited a transduction efficiency much higher than the original vector, rAd5-B19NS1-GFP, in UT7/Epo-S1 cells, in particular, when they were transduced at a relatively low multiplicity of infection (100 viral genome copies/cell). After the transduction of rAd5F11p-B19NS1-GFP, over 90% of the UT7/Epo-S1 cells were arrested at the G2/M phase, and approximately 40%-50% of the cells were undergoing apoptosis, suggesting the novel rAd5F11P-B19NS1-GFP vector holds a promise in therapeutic potentials of megakaryocytic leukemia.

5.
Bioorg Med Chem ; : 114938, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31488358

RESUMO

4-Anilinoquinazoline derivatives function as tyrosine kinase inhibitors (TKIs). Novel TKIs are needed for cancer mutations and drug-resistant cells. We designed and synthesized 4-anilinoquinazoline derivatives with substitutions at quinazoline positions 6, 7 and 4 using a binding model with multi-target receptor tyrosine kinases, and assessed their antitumor activity against five human tumor cell lines (HepG2, A549, MCF-7, DU145, SH-SY5Y). The majority of the compounds inhibited the proliferation of all the cancer cell types, with some compounds displaying selective inhibition. Compounds 21, 25, 27, and 37 displayed IC50 values of 7.588, 8.619, 6.936, and 8.516 µM, respectively, for A549 cells, which were much lower than that of Gefitinib (14.803 µM). Compound 32 displayed an IC50 value of 2.756 µM for DU145 cells. The representative compound 40 had unexceptionable broad-spectrum inhibition for all cancer cell types, and demonstrate inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFR-ß), and epidermal growth factor receptor (EGFR) with IC50 values of 46.4, 673.6 and 384.8 nM, respectively, which were similar to those of Sorafenib for VEGFR-2 and PDGFR-ß (140.6 and 582.7 nM, respectively). Molecular docking results supported the molecular level assay results. Data for production of reactive oxygen species and assessment of matrix metalloproteinase corroborated the strong anti-proliferative effect of compound 40. The compound also displayed robust antitumor efficacy and relativity lower toxicity in a xenograft model. These attributes were similar to those of Sorafenib. Compound 40 drug warrants further study as a candidate.

6.
J Invest Dermatol ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476315

RESUMO

Distant metastases are responsible for the majority of melanoma mortalities. As a critical barrier against metastasis, anoikis is a distinct programmed cell death induced by the integrated stress from extracellular matrix (ECM) detachment. In order to survive, tumor cells employ various strategies for overcoming this barrier. Recently, Sestrin2(Sesn2) has been reported to play a protective role against integrated stress. In this study, we found ECM detachment triggered the up-regulation of Sesn2 in metastatic melanoma cells. Knockdown of Sesn2 impaired not only the cell viability but also the tumor sphere formation of melanoma cells in suspension cultures. Moreover, an elevated oxidative stress level was detected in Sesn2-silencing melanoma cells in suspension cultures, accompanied with an increased apoptosis rate. Last of all, in vivo studies indicated that Sesn2-knockdown remarkably reduced the formation of distant metastasis. Taken together, our findings illustrated that the up-regulation of Sesn2 in response to suspension stress plays a protective role in melanoma against anoikis by detoxifying oxidative stress.

7.
Sci Rep ; 9(1): 13046, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506455

RESUMO

The fabella is a sesamoid bone of the knee that can degenerate in some patients with osteoarthritis. The purpose of this study was to examine the prevalence and degeneration grades of fabellae in the Chinese population and to analyse their relationships with subject ages and knee osteoarthritis grades. The anteroposterior and lateral knee roentgenograms of 1150 subjects were recruited from the institutional database. The Kellgren-Lawrence scoring system was used to evaluate knee osteoarthritis. The degeneration grades of fabellae were scored in lateral roentgenograms by screening their shapes, sizes, subchondral sclerosis and osteophyte formation. The prevalence and degeneration of fabellae among ages, genders and knee sides were analysed by the Pearson Chi-Square test, and their relationships with knee osteoarthritis were analysed by the Spearman nonparametric correlation test. The overall prevalence of fabellae was 48.6% in 1359 knees. There was no significant difference in fabellar prevalence between the two sides (χ² = 0.025, P = 0.87437) and genders (χ² = 3.647, P = 0.05617), while the prevalence increased with the increasing ages of the subjects (χ² = 213.868, P < 0.001). The fabellar degeneration grades were correlated with age (r = 0.5288, P < 0.001) and knee osteoarthritis scores (r = 0.6892, P < 0.001). These results suggested that the fabellar prevalence and degeneration grades were correlated with age and knee osteoarthritis scores.

8.
J Phys Chem A ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31497961

RESUMO

Many-body dispersion has gained considerable attention over the past decade, particularly for condensed phase systems. However, quantitatively accurate studies of many-body dispersion have only recently become feasible due to challenges in reliability and accuracy. Currently available methodologies for calculating many-body dispersion have been challenged, with recent evidence suggesting, for example, that dispersion-corrected density functional theory (DFT) schemes cannot consistently predict many-body dispersion accurately. This study evaluates many-body dispersion energies using a composite approach that employs singles and doubles coupled cluster theory with perturbative/non-iterative triples, CCSD(T), combined with an extrapolation to the complete basis set (CBS) limit. The combined CCSD(T)/CBS approach is applied to Arn and (H2O)n, n=3-10, clusters, and a new dataset called S22(3), which includes trimers generated based on the S22 dataset. In these systems, the many-body dispersion provides a very small contribution to the total interaction energy of all of the systems studied, generally 3% or less of the total interaction energy. Two-body dispersion is the dominant dispersion contribution and many-body dispersion contributes no more than 5.7% of the total dispersion energy, generally staying below 2%. .

9.
Clin Cancer Res ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444250

RESUMO

PURPOSE: Anti-CD19 chimeric antigen receptor (CAR) T cells represent a novel immunotherapy and are highly effective in treating relapsed/refractory B-cell non- Hodgkin's lymphoma (B-NHL). How tumor microenvironment influences clinical response to CAR T therapy remains great interests. EXPERIMENTAL DESIGN: Aphase 1, first-in-human, dose-escalation studyof anti-CD19 JWCAR029was conductedinrefractory B-NHL (NCT03355859)and 10 patients received CAR T cells at an escalating dose of 2.5X107(n=3), 5X107(n=4), and 1X108(n=3) cells.Core needle biopsy was performed on tumor samples collected from diffuse large B-cell lymphomapatients onDay -6 (one day before lymphodepletion) and on Day 11 after CAR T cell infusion when adequate CAR T cell expansion was detected. RESULTS: The overall response rate was 100%, with 6 of 9 (66.7%) evaluable patients achieved complete remission. The most common adverse events of grade 3 or higher were neutropenia (10/10, 100%), anemia (3/10, 30%), thrombocytopenia (3/10, 30%), and hypofibrinogenemia (2/10, 20%). Grade 1 CRS occurred in all patientsand grade 3 neurotoxicity in one patient. The average peak levels of peripheral blood CAR T cells and cytokines were similar in three different dose levels,but CART cells were significantly higher in patients achieved CR on Day 29. Meanwhile, RNA sequencing identified gene expression signatures differentially enriched in complete and partial remission patients.Increased tumor-associated macrophage infiltration was negatively associated with remission status. CONCLUSIONS: JWCAR029was effective and safe in treating refractory B-NHL. The composition of the tumor microenvironment has a potential impact inCAR T therapy response.

10.
Nat Commun ; 10(1): 3751, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434894

RESUMO

Synthetic biology aims to develop programmable tools to perform complex functions such as redistributing metabolic flux in industrial microorganisms. However, development of protein-level circuits is limited by availability of designable, orthogonal, and composable tools. Here, with the aid of engineered viral proteases and proteolytic signals, we build two sets of controllable protein units, which can be rationally configured to three tools. Using a protease-based dynamic regulation circuit to fine-tune metabolic flow, we achieve 12.63 g L-1 shikimate titer in minimal medium without inducer. In addition, the carbon catabolite repression is alleviated by protease-based inverter-mediated flux redistribution under multiple carbon sources. By coordinating reaction rate using a protease-based oscillator in E. coli, we achieve D-xylonate productivity of 7.12 g L-1 h-1 with a titer of 199.44 g L-1. These results highlight the applicability of programmable protein switches to metabolic engineering for valuable chemicals production.

11.
Medicine (Baltimore) ; 98(34): e15852, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441836

RESUMO

BACKGROUND: The purpose of this study was to investigate the benefits and harm of combined administration of tranexamic acid (TXA) and dexamethasone (Dexa) in total knee arthroplasty (TKA). METHODS: A total of 88 consecutive patients undergoing TKA for knee osteoarthritis were stratified in 2 groups. All surgeries were performed under general anesthesia. Brief, patients in the TXA + Dexa group (n = 45) received 10 mg Dexa just after the anesthesia, and repeated at 24 hours after the surgery; and patients in the TXA group (n = 43) received 2 ml of normal saline solution at the same time. The measured outcomes were the C-reactive protein (CRP) and interleukin-6 (IL-6) from preoperatively to postoperatively, and postoperative nausea and vomiting (PONV), fatigue, range of motion (ROM), length of stay (LOS), and the analgesic and antiemetic rescue consumption RESULTS:: The level of CRP and IL-6 in the TXA + Dexa group were lower than that in the TXA group at 24 hours (P < .001, P < .001), 48 hours (P < .001, P < .001), and 72 hours (P < .001, P < .001) after the surgery. The pain scores in the TXA + Dexa group were lower during walking at 24 hours (P < .001), 48 hours (P < .001), and 72 hours (P < .001) and at rest at 24 hours (P = .022) after the surgery. Patients in the TXA + Dexa group had a lower nausea score, the incidence of PONV, fatigue, and the analgesic and antiemetic rescue consumption, and had a greater ROM than that in the TXA group. No significant differences were found in LOS and complications. CONCLUSION: The combined administration of TXA + Dexa significantly reduced the level of postoperative CRP and IL-6, relieve postoperative pain, ameliorate the incidence of POVN, provide additional analgesic and antiemetic effects, reduce postoperative fatigue, and improve ROM, without increasing the risk of complications in primary TKA.

12.
Sci Rep ; 9(1): 11871, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417129

RESUMO

Transport fluxes and properties of riverine organic carbon in the tropical monsoon region were the vital parameters in the global riverine organic carbon fluxes budget. The study focused on the riverine organic carbon in the Changhuajiang River (CHJR), locating at the mid-west of the Hainan Island, China. Dissolved organic carbon (DOC) concentrations in the CHJR ranged from 0.22 mg/L to 11.75 mg/L with an average of 1.75 mg/L, which was lower than the average of global rivers and had a significantly temporal and spatial variation. Output flux of riverine DOC was calculated as 0.55 t/km2/y, which could be revised up to 1.03 t/km2/y, considering that the riverine discharge before dam construction. A linear model of riverine DOC flux suitable in CHJR basin was established, which involved the factors, such as soil organic carbon, runoff depth and slope, etc. There was a large variation of POC concentrations in the CHJR where the average POC concentration in the dry season was 2.41 times of the wet season. Riverine POC flux in CHJR basin was calculated as 1.78 t/km2/y, higher than the average of global rivers and far lower than those in other domestic larger rivers. About 8.28 × 103 t POC were exported yearly in CHJR, of which, 7.15 × 103 t originated from terrestrial ecosystem and 1.13 × 103 t stemmed from aquatic ecosystem. Meanwhile, about 87.74% of terrestrial source happened in the wet season and 12.26% in the dry season. This research revealed that the riverine organic carbon mainly stemmed from the surface erosion processes in the drainage basin during the wet season.

13.
PLoS Negl Trop Dis ; 13(8): e0007634, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31369553

RESUMO

BACKGROUND: Oral cholera vaccine (OCV) containing killed Vibrio cholerae O1 and O139 organisms (Bivalent-OCV; Biv-OCV) are playing a central role in global cholera control strategies. OCV is currently administered in a 2-dose regimen (day 0 and 14). There is a growing body of evidence that immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae mediate protection against cholera. There are limited data on anti-OSP responses in recipients of Biv-OCV. We assessed serum antibody responses against O1 OSP, as well as antibody secreting cell (ASC) responses (a surrogate marker for mucosal immunity) and memory B cell responses in blood of adult recipients of Biv-OCV in Dhaka, Bangladesh. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 30 healthy adults in this study and administered two doses of OCV (Shanchol) at days 0 and 14. Blood samples were collected before vaccination (day 0) and 7 days after each vaccination (day 7 and day 21), as well as on day 44. Serum responses were largely IgA with minimal IgG and IgM responses in this population. There was no appreciable boosting following day 14 vaccination. There were significant anti-OSP IgA ASC responses on day 7 following the first vaccination, but none after the second immunization. Anti-OSP IgA memory B cell responses were detectable 30 days after completion of the vaccination series, with no evident induction of IgG memory responses. In this population, anti-Ogawa OSP responses were more prominent than anti-Inaba responses, perhaps reflecting impact of previous exposure. Serum anti-OSP responses returned to baseline within 30 days of completing the vaccine series. CONCLUSION: Our results call into question the utility of the 2-dose regimen separated by 14 days in adults in cholera endemic areas, and also suggest that Biv-OCV-induced immune responses targeting OSP are largely IgA in this highly endemic cholera area. Studies in children in cholera-endemic areas need to be performed. Protective efficacy that extends for more than a month after vaccination presumably is mediated by direct mucosal immune response which is not assessed in this study. Our results suggest a single dose of OCV in adults in a cholera endemic zone may be sufficient to mediate at least short-term protection.

14.
Metab Eng ; 56: 60-68, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31470116

RESUMO

Acetyl-CoA is the central metabolic node connecting glycolysis, Krebs cycle and fatty acids synthase. Plant-derived polyketides, are assembled from acetyl-CoA and malonyl-CoA, represent a large family of biological compounds with diversified bioactivity. Harnessing microbial bioconversion is considered as a feasible approach to large-scale production of polyketides from renewable feedstocks. Most of the current polyketide production platform relied on the lengthy glycolytic steps to provide acetyl-CoA, which inherently suffers from complex regulation with metabolically-costly cofactor/ATP requirements. Using the simplest polyketide triacetic acid lactone (TAL) as a testbed molecule, we demonstrate that acetate uptake pathway in oleaginous yeast (Yarrowia lipolytica) could function as an acetyl-CoA shortcut to achieve metabolic optimality in producing polyketides. We identified the metabolic bottlenecks to rewire acetate utilization for efficient TAL production in Y. lipolytica, including generation of the driving force for acetyl-CoA, malonyl-CoA and NADPH. The engineered strain, with the overexpression of endogenous acetyl-CoA carboxylase (ACC1), malic enzyme (MAE1) and a bacteria-derived cytosolic pyruvate dehydrogenase (PDH), affords robust TAL production with titer up to 4.76 g/L from industrial glacier acetic acid in shake flasks, representing 8.5-times improvement over the parental strain. The acetate-to-TAL conversion ratio (0.149 g/g) reaches 31.9% of the theoretical maximum yield. The carbon flux through this acetyl-CoA metabolic shortcut exceeds the carbon flux afforded by the native glycolytic pathways. Potentially, acetic acid could be manufactured in large-quantity at low-cost from Syngas fermentation or heterogenous catalysis (methanol carbonylation). This alternative carbon sources present a metabolic advantage over glucose to unleash intrinsic pathway limitations and achieve high carbon conversion efficiency and cost-efficiency. This work also highlights that low-cost acetic acid could be sustainably upgraded to high-value polyketides by oleaginous yeast species in an eco-friendly and cost-efficient manner.

15.
BMC Nephrol ; 20(1): 287, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362703

RESUMO

BACKGROUND: Many patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) need dialysis at disease onset due to severe kidney injury. Determining whether they can become dialysis independent is an important clinical assessment. METHODS: Forty kidney biopsy-proved myeloperoxidase (MPO)-ANCA associated AAV patients who required dialysis at disease onset were enrolled. Relationships between laboratory and pathological characteristics and prognoses were analyzed. RESULTS: Twenty-five patients obtained dialysis independence within 3 months, while the other 15 patients remained dialysis dependent. No sclerotic class was identified among the 40 patients. Only two biopsies exhibited focal class diagnoses and both these patients recovered their renal function. The renal recovery rate of the 20 patients with mixed class was significantly lower than that of the 18 patients with crescentic class (40.0% vs. 83.3%, p = 0.006). Receiver operating characteristics (ROC) curves showed fibrous crescent+global glomerulosclerosis greater than 32.6% was a strong predictor of dialysis dependence with a sensitivity of 93.3% and specificity of 88.0%. When the percentage of fibrous crescent+global glomerulosclerosis exceeded 47.9%, dialysis independence was not possible. Correlation analysis indicated that platelet counts were negatively correlated with the percentage of fibrous crescent+global glomerulosclerosis (R = -0.448, p = 0.004). Most patients with increased platelets (84.62%) obtained renal recovery. Compared with methylprednisolone pulse therapy, plasma exchange accelerated renal recovery (29.4 ± 15.6 vs. 41.4 ± 11.7 days, p = 0.039). CONCLUSIONS: For MPO-ANCA AAV who required dialysis at disease onset, crescentic and mixed classes accounted for the majority of patients in our cohort. The renal outcome of mixed class patients was worse than that of crescentic class. A high proportion of fibrous crescent+global glomerulosclerosis is a predictor of dialysis dependence. Increased platelet count is associated with active and reversible renal lesions.

16.
Traffic Inj Prev ; 20(sup1): S27-S31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31381455

RESUMO

Objective: Fatal brain injuries result from physiological changes in brain tissues, subsequent to primary damage caused by head impact. Although efforts have been made in past studies to estimate the probability of brain injury, none of them involved prediction of such physiological changes. The goal of this study was to evaluate the fatality prediction capability of a novel approach that predicts an increase in intracranial pressure (ICP) due to primary head injury to estimate the fatality rate using clinical data that correlate ICP with fatality rate. Methods: A total of 12 sets of head acceleration time histories were used to represent no, severe, and fatal brain injury. They were obtained from the literature presenting head kinematics data in noninjurious volunteer sled tests or from accident reconstruction for severe and fatal injury cases. These were first applied to a Global Human Body Models Consortium (GHBMC) head-brain model to predict nodal displacement time histories of the brain, which were then fed into FEBio to predict ICP. A Weibull distribution was applied to the data for the relationship between fatality rate and ICP obtained from a clinical paper to estimate fatality rate from ICP (procedure A). Fatality rate was also estimated by applying the temporal and spatial maximum value of maximum principal strain (MPSmax) obtained from the GHBMC simulation to an injury probability function for MPSmax (procedure B). Estimated fatality rates were compared between the 2 procedures. Results: Both procedures estimated higher average fatality rate for higher injury severity. The average fatality rate for procedure A without ischemia representation and procedure B was 72.4 and 51.0% for the fatal injury group and 8.2 and 21.7% for the severe injury group, respectively, showing that procedure A provides more distinct classification between fatal and nonfatal brain injury. It was also found that representation of ischemia in procedure A provides results sensitive to injury severity and impact conditions, requiring further validation of the initial estimate for the relationship between brain compression and ischemic cell death. Conclusions: Prediction of the probability of fatality by means of a combination of simulations of the primary brain deformation and subsequent ICP increase was found to be more distinct compared to the prediction of primary injury alone combined with the injury probability function from a past study in the select 12 head impact cases.

17.
Chemosphere ; 237: 124509, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31400741

RESUMO

A novel system combined with photocatalytic fuel cell and electrochemical system assisted by reverse electrodialysis (PREC) is proposed for H2O2 production and electricity generation. Results demonstrated the H2O2 concentration increased gradually with time and reached around 940 mg/L at 24 h. The optimum air flow rate was 15 L/min. The current efficiency was 31.3%. The maximum short-circuit current density, maximum open-circuit voltage and maximum power density were 0.95 mA/cm2, 1.52 V and 68 W/m2. The salinity-driven potential, created with the five pairs of the HC and LC cells in the PREC, was calculated to be 0.72 V. Additionally, the energy efficiency (ηE) was 40.5%. The integrated system is confirmed to be serviced as an efficient technology for H2O2 electro-genneration and salinity-gradient energy utilization simultaneously.

18.
Trends Microbiol ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31421969

RESUMO

Rapid advances in DNA synthesis, genetic manipulation, and biosensors have greatly improved the ability to engineer microorganisms with complex functions. By accurately integrating quality biosensors and complex genetic circuits, recently emerged smart microorganisms have enabled exciting opportunities for dissecting complex signaling networks and making responses without artificial intervention. However, because of the lack of design principles, developing such smart microorganisms remains challenging. In this review, we propose the concept of smart microbial engineering (SME) and describe the general features of basic SME, including the circuit architecture, components, and design process. We also summarize the latest SME achievements, remaining challenges, and potential solutions in this growing field.

19.
Biomed Pharmacother ; 118: 109232, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31369987

RESUMO

Triptolide(T9) is a predominant bioactive component extracted from Chinese herb Tripterygium wilfordii Hook F. (TwHF), and has multiple pharmacological activities, such as immunosuppressive and anti-inflammatory activities, et al. However, severe adverse effects and toxicity, particularly nephrotoxicity, limit its clinical application. It has been demonstrated that the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway could alleviate T9-induced nephrocyte damage. The aim of this study was to investigate the potential protective role of triptriolide (T11) against T9-induced nephrocyte apoptosis in vitro and in vivo. Renal injury models were established in human kidney 2 (HK2) cells and BALB/c mice using T9, and the protective effects of T11 were probed in vitro and in vivo, respectively. T9 induced nephrocyte damage in HK2 cells and BALB/c mice by induction of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA) and glutathione (GSH) and reduction of superoxide dismutase (SOD), which resulted in the apoptosis of nephrocyte and injury of renal function. While, pretreatment of T11 effectively reversed these changes, resulting in the obvious decrease of oxidative stress and renal function parameters, ameliorated nephrocyte apoptosis, improved cell morphology, and higher increase of Nrf2, NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) protein levels in vitro and in vivo. Altogether, T11 protected against T9-induced nephrocyte apoptosis possibly via suppressing oxidative stress.

20.
Medicine (Baltimore) ; 98(31): e16543, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374016

RESUMO

BACKGROUND: Number of studies have been performed to investigate the relationship between the CYP1A1 rs4646903 polymorphism and male infertility risk, but the sample size was small and the results were conflicting. A meta-analysis was performed to assess these associations. METHODS: A systematic search was conducted to identify all relevant studies from Medline, Web of science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), WanFang and Weipu (VIP) databases up to June 30, 2018. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of associations. All of the statistical analyses were conducted using Revman 5.3 and Stata 14.0. RESULTS: Ten studies involved 3028 cases and 3258 controls. Overall, significant association was observed between the CYP1A1 rs4646903 polymorphism and male infertility (C vs T: OR = 1.42, 95%CI = 1.14-1.76; CC vs TT: OR = 2.13, 95%CI = 1.36-3.34; CC vs CT+TT: OR = 1.96, 95%CI = 1.30-2.95; CC+CT vs TT: OR = 1.51, 95%CI = 1.16-1.97). In subgroup analysis by ethnic group, a statistically significant association was observed in Asians (C vs T: OR = 1.59, 95%CI = 1.22-2.08), but not in Non-Asians (C vs T: OR = 1.01, 95%CI = 0.79-1.30). Additionally, none of the individual studies significantly affected the association between CYP1A1 rs4646903 polymorphism and male infertility, according to sensitivity analysis. CONCLUSION: Our meta-analysis supports that the CYP1A1 rs4646903 polymorphism might contribute to individual susceptibility to male infertility in Asians.


Assuntos
Citocromo P-450 CYP1A1/genética , Infertilidade Masculina/etiologia , Infertilidade Masculina/genética , Predisposição Genética para Doença , Humanos , Masculino , Razão de Chances
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