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1.
J Natl Compr Canc Netw ; 17(9): 1100-1108, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31487686

RESUMO

BACKGROUND: Population-based studies suggest that patients with multiple myeloma (MM) have better outcomes when treated at high-volume facilities, but the relative contribution of provider expertise and hospital resources to improved outcomes is unknown. This study explored how treating facility, individual provider volume, and patient-sharing between MM specialists and community providers influenced outcomes for patients with MM. PATIENTS AND METHODS: A state cancer registry linked to public and private insurance claims was used to identify a cohort of patients diagnosed with MM in 2006 through 2012. Three multivariable Cox models were used to examine how the following factors impacted overall survival: (1) evaluation at an NCI-designated Comprehensive Cancer Center (NCICCC), (2) the primary oncologist's volume of patients with MM, and (3) patient-sharing between MM specialists and community oncologists. RESULTS: A total of 1,029 patients diagnosed with MM in 2006 through 2012 were identified. Patients who were not evaluated at an NCICCC had an increased risk of mortality compared with those evaluated at an NCICCC (hazard ratio [HR], 1.50; 95% CI, 1.21-1.86; P<.001). Compared with patients treated by NCICCC MM specialists, those treated by both low-volume community providers (HR, 1.47; 95% CI, 1.14-1.90; P<.01) and high-volume community providers (HR, 1.29; 95% CI, 1.04-1.61; P<.05) had a higher risk of mortality. No difference in mortality was seen between patients treated by NCICCC MM specialists and those treated by the highest-volume community oncologists in the ninth and tenth deciles (HR, 1.08; 95% CI, 0.84-1.37; P=.5591). Patients treated by community oncologists had a higher risk of mortality regardless of patient-sharing compared with patients treated by MM specialists (eg, community oncologist with a history of sharing vs NCICCC MM specialist: HR, 1.49; 95% CI, 1.10-2.02; P<.05). CONCLUSIONS: Findings of this study add to the accumulating evidence showing that patients with MM benefit from care at high-volume facilities, and suggest that similar outcomes can be achieved by the highest-volume providers in the community.

2.
Vet Microbiol ; 235: 220-228, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383305

RESUMO

The highly virulent porcine epidemic diarrhea virus (PEDV) variants cause the death of mainly neonatal piglets, but how the viruses spread within the gastro-intestinal tract in a temporal and spatial manner has remained poorly characterized but is critical to understand the viral pathogenesis. In this study, we used the Chinese PEDV epidemic strain BJ2011C as a model organism and took advantage of the newly developed RNAscope in situ hybridization technology to investigate the tempo-spatial infection dynamics in neonatal piglets. We found that the PEDV strain BJ2011C could quickly colonize the small intestine, which occurred in just 6 h post infection, with virus shedding starting at 6 hpi and peaking at 24 hpi. Jejunum was the first target tissue for infection and then ileum, followed by infrequent infection of duodenum. In these tissues, the virus nucleic acids were mainly present in the villous epithelial cells but not in crypt cells. Interestingly, the viral RNAs were not detectable by RNAscope in large intestines although tissue damages could be discerned by H & E staining. Overall, our results provide useful information about spread dynamics and tissue preference of PEDV epidemic strain BJ2011C.

3.
Shanghai Kou Qiang Yi Xue ; 28(2): 184-186, 2019.
Artigo em Chinês | MEDLINE | ID: mdl-31384906

RESUMO

PURPOSE: This study was to explore the role of Er, Cr:YSGG water laser in relieving endodontic interappointment pain (EIAP) during root canal therapy. METHODS: A total of 272 cases with chronic pulpitis and chronic periapical periodontitis were selected from the Department of Endodontics of our hospital from June 2015 to June 2017, they were randomly divided into 2 groups, 136 cases in each group. After routine root canal preparation, the teeth in group A were sealed with calcium hydroxide paste after Er, Cr : YSGG water laser treatment, while teeth in group B were sealed with calcium hydroxide paste. Caviton (GC company, Japan) was used for temporary fillings in both groups, occurrence and outcomes of postoperative EIAP were recorded and compared. SPSS 17.0 software package was used for statistical analysis. RESULTS: Among the two groups, there was no significant differences in EIAP (P>0.05) immediately and 1 week after surgery, but there was significant difference in the occurrence of EIAP between the first day, the second day and the third day after surgery (P<0.05). Group A had the lowest incidence of EIAP. CONCLUSIONS: Er, Cr: YSGG water laser can effectively reduce pain after root canal therapy, and can effectively shorten pain duration for patients; therefore, it is worthy of wide clinical application.

4.
Mult Scler Relat Disord ; 35: 246-252, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31425902

RESUMO

BACKGROUND: Several immunosuppressants or monoclonal antibodies have been used as preventive treatment for neuromyelitis optica spectrum disorders (NMOSD); however, the optimal therapies have not been clarified. In this study, we aimed to compare and rank the effectiveness and tolerability of all preventive therapies for NMOSD. METHODS: Qualified studies were identified in a search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases. We combined direct and indirect evidence via meta-analyses. The annualized relapse rate (ARR) was defined as the primary outcome. Secondary outcomes included the Expanded Disability Status Scale (EDSS) score and hazard ratios (HR) for the counts of adverse events (AEs). RESULTS: We identified one randomized controlled trial (RCT) and five observational studies including a total 631 patients with NMOSD. Among these, the follow-up time ranged from 12 to 40 months. For the primary outcome, rituximab (RTX) was hierarchically superior, with the significant standardized mean difference versus azathioprine (-0.86; 95% confidence interval: -1.60, -0.11). Mycophenolate mofetil (MMF) was ranked the most tolerable therapy, whereas cyclophosphamide was the least tolerable. CONCLUSION: RTX and MMF may be recommended as optimal treatments to prevent relapse in NMOSD. Low-dose cyclosporine A could be a promising alternative therapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31430942

RESUMO

Village resettlement communities (VRCs) are a special type of urban community that the government has promoted considerably during China's rapid urbanization. This study uses the theory of the production of space as a basis to explore the processes and mechanisms of the physical and social space evolution of VRCs through a case study of Qunyi Community, one of the largest VRCs in Kunshan. Questionnaires and semi-structured interviews were employed in this study. Results indicate that the coupling relationship between local government power and diversified capital is the fundamental reason that promotes the production of macrophysical space. Moreover, the economic and social relationships among residents promote the reproduction of microsocial space. Landless farmers are the most important spatial producers in the microsocial space. The individual needs and cultural differences of immigrant workers also have significant effects on microspatial production. Furthermore, the production and reproduction of the physical and social spaces, respectively, of VRCs deduce the adjustment relationship among the urbanization processes of land, population, and individuals. Results also indicate that the urbanization of individuals appears to lag behind the previous two processes. This study can provide a theoretical basis for the spatial renovation and management optimization of VRCs, as well as the promotion of a new type of "people-centered" urbanization.

6.
Hepatology ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31469916

RESUMO

Most tumor cells use aerobic glycolysis (the Warburg effect) to support anabolic growth and promote tumorigenicity and drug resistance. Intriguingly, the molecular mechanisms underlying this phenomenon are not well understood. In this work, using gain- and loss-of-function in vitro studies in patient-derived organoid and cell cultures as well as in vivo PET-MRI animal models, we showed that PRMT6 regulates aerobic glycolysis in human hepatocellular carcinoma (HCC) through nuclear relocalization of pyruvate kinase M2 isoform (PKM2), a key regulator of the Warburg effect. We found PRMT6 to methylate CRAF at arginine 100, interfere with its RAS/RAF binding potential and as a result alter ERK-mediated PKM2 translocation into the nucleus. This altered PRMT6-ERK-PKM2 signaling axis was further confirmed in both a HCC mouse model with endogenous knockout of PRMT6 as well as in HCC clinical samples. We also identified PRMT6 as a novel target of hypoxia via the transcriptional repressor REST, linking PRMT6 with hypoxia in driving glycolytic events. Finally, we showed as a proof-of-concept the therapeutic potential of using 2-deoxyglucose (2DG), a glycolysis inhibitor, to reverse tumorigenicity and sorafenib resistance mediated by PRMT6 deficiency in HCC. CONCLUSION: Our findings indicate that the PRMT6-ERK-PKM2 regulatory axis is an important determinant of the Warburg effect in tumor cells and provide a mechanistic link between tumorigenicity, sorafenib resistance and glucose metabolism. This article is protected by copyright. All rights reserved.

7.
Sci Rep ; 9(1): 11348, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383886

RESUMO

We aimed to compare the efficacy of percutaneous transhepatic biliary stenting (PTBS) and PTBS combined with 125I particles implantation in the treatment of advanced extrahepatic cholangiocarcinoma (EHC). A total of 184 advanced EHC patients, who received PTBS (PTBS group) or PTBS combined with 125I particles implantation (PTBS + 125I group) from January 2012 to April 2017 in our department, were retrospectively reviewed. The improvement of jaundice and liver function was observed in both groups. The postoperative complications, risk of biliary re-obstruction, and overall survival (OS) were compared between the two groups. Amongst, 71 cases received PTBS and 113 had the additional implantation of 125I particles. The jaundice and liver function were significantly improved in all patients, especially in PTBS + 125I group. There was no significant difference in the risk of postoperative complications between the two groups. However, the risk of biliary re-obstruction significantly reduced in PTBS + 125I group (19.5% vs. 35.2%, p = 0.017). Kaplan Meier analysis showed that patients in PTBS + 125I group had a significantly better OS, both for hilar and distal cholangiocarcinoma. Univariate analysis demonstrated that preoperative levels of carbohydrate antigen 19-9 (CA19-9), total bilirubin, neutrophil count, lymphocyte count, and different therapeutic method were significant factors affecting OS. Multivariate analysis further identified the treatment of PTBS combined with 125I particles implantation as an independent protective prognostic factor (HR = 0.26, 95% CI: 0.17-0.39, p < 0.001). In conclusion, for patients with advanced EHC, PTBS combined with 125I particles implantation is superior to PTBS alone in improving liver function, inhibiting biliary re-obstruction, and prolonging survival time.

8.
Biomed Pharmacother ; 117: 109181, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387196

RESUMO

BACKGROUND: Rosacea is a facial chronic inflammatory skin disease with dysfunction of immune and vascular system. Artemisinin (ART), an anti-malaria drug, was reported to have several effects including anti-inflammation and anti-angiogenesis activities. However, the role of ART on rosacea remains unclear. OBJECTIVES: To investigate the effects and molecular mechanism of ART on rosacea. METHOD: In rosacea-like mouse model, the phenotype of rosacea lesions was evaluated by redness score, the inflammatory biomarkers were analyzed by qPCR, and the infiltration of inflammatory cells were assessed by IHC analysis and immunofluorescence. In vitro, LL37-induced expression of inflammatory factors in HaCaT cells was detected by qPCR, potential signaling pathways were detected by Western blotting or immunofluorescence. Migration ability of human umbilical vein endothelial cells (HUVECs) was evaluated by cell scratch and transwell assays. RESULT: The skin erythema and histopathological alteration, as well as the elevated pro-inflammatory factors (IL-1ß, IL6, TNFα) and TLR2 were significantly ameliorated by ART treatment in LL37-induced rosacea-like mice. In addition, ART reduced the infiltration of CD4+ T cells, macrophages and neutrophils, and repressed the expression of immune cells related chemokines (CXCL10, CCL20, CCL2 and CXCL2) in mouse lesions. In HaCaT cells, ART significantly decreased the LL37-induced expression of inflammatory biomarkers. Moreover, we found that ART inhibited rosacea-like inflammation via NF-kB signaling pathways in HaCaT cells. Finally, for vascular dysregulation, ART repressed the angiogenesis in mouse model and inhibited the LL37-induced HUVECs migration in vitro. CONCLUSION: ART ameliorated rosacea-like dermatitis by regulating immune response and angiogenesis, indicating that it could represent an effective therapeutic option for patients with rosacea.

9.
Food Chem ; 303: 125401, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31466031

RESUMO

Salt addition and thermal pretreatment were used to improve the freeze-thaw stability of Pickering emulsion gels (PEGs) stabilized by compound proteins. Thermal pretreatment with the presence of salt could promote the formation of gel-like structure and alter the interactions between the emulsion droplets of PEGs, sequentially increase the resistance of the PEGs to water separation, creaming, and oiling-off during freeze-thaw cycles (freeze at -20 °C for 22 h and thawing at 37 °C for 2 h), especially at higher salt levels (200 and 500 mM). Microstructures indicated that the presence of high salt concentration and heat pretreatment could help to maintain the gel-like structures of PEGs during freeze-thaw cycles. Overall, our results showed that novel viscoelastic food materials with good freeze-thaw stability can be produced by controlling the electrostatic interactions between the emulsion droplets and the gelation of emulsion gels. These materials may be useful for application in frozen food products.

10.
Biopolymers ; : e23328, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454076

RESUMO

Blood vessels play an important role in bone defect repair and growth, and a critical challenge of bone defect repair is the promotion of blood vessel formation. Most of the current methods promote vascularization by adding specific growth factors, which are costly and easy to inactivate. In this study, we developed a covalently cross-linked aminated bioactive glass nanoparticle-chondroitin sulfate methacrylate (ABGN-CSMA) organic-inorganic composite hydrogel with angiogenic properties. The amino groups of the ABGNs form covalent bonds with the carboxyl groups on CSMA. Surface amination modification of BGNs not only improved the dispersion of BGNs in CSMA but also significantly improved the mechanical properties of the composite hydrogel. The largest storage modulus (1200 Pa), the largest loss modulus (560 Pa) and the strongest resistance to deformation of the hydrogel are seen at 10% concentration of ABGNs. Simultaneously, the local pH stability and sustained ion release of the composite hydrogel are conducive to cell adhesion, proliferation, and angiogenesis. This work provides evidence for the development of covalently cross-linked organic-inorganic composite hydrogels with angiogenic properties.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31448499

RESUMO

Low-dimensional lead halide perovskite materials recently have drawn much attention owing to the intriguing broadband emissions, however, the toxicity of lead will hinder their future development. Herein we report a novel lead-free (C 4 H 14 N 2 ) 2 In 2 Br 10 single crystal with a unique zero-dimensional (0D) structure constituted by [InBr 6 ] 3- octahedral and [InBr 4 ] - tetrahedral units. The single crystal exhibits broadband photoluminescence (PL) almost spanning the whole visible spectrum with a lifetime of 3.2 µs. Computational and experimental studies unveil that an excited-state structural distortion in [InBr 6 ] 3- octahedral units enables the formation of intrinsic self-trapped excitons (STEs) and thus contributing the broad emission. Furthermore, femtosecond transient absorption (fs-TA) measurement reveals that the ultrafast STEs formation together with an efficient intersystem crossing has made a significant contribution to the long-lived and broad STE-based emission behavior. These results not only provide a novel lead-free luminescent material but also shed light on the relationship between structure and PL property.

12.
J Am Chem Soc ; 141(34): 13434-13441, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31378058

RESUMO

Heterojunction engineering has played an indispensable role in the exploitation of innovative artificial materials with exceptional properties and has consequently triggered a new revolution in achieving high-performance optoelectronic devices. Herein, an intriguing halide perovskite (PVK) and metal dichalcogenide (MD) heterojunction, i.e., a lead-free Cs2SnI6 perovskite nanocrystal/SnS2 nanosheet hybrid, was fabricated in situ for the first time. Comprehensive investigations with experimental characterizations and theoretical calculations demonstrate that cosharing of the Sn atom enables intimate contact in the Cs2SnI6/SnS2 hybrid together with a type II band alignment structure. Additionally, ultrafast carrier separation between SnS2 and Cs2SnI6 has been observed in the Cs2SnI6/SnS2 hybrid by transient absorption measurements, which efficiently prolongs the lifetime of the photogenerated electrons in SnS2 (from 1290 to 3080 ps). The resultant spatial charge separation in the Cs2SnI6/SnS2 hybrid evidenced by Kelvin probe force microscopy (KPFM) significantly boosts the photocatalytic activity toward CO2 reduction and the photoelectrochemical performance, with 5.4-fold and 10.6-fold enhancements compared with unadorned SnS2. This work provides a facile and effective method for the in situ preparation of PVK-MD heterojunctions, which may significantly stimulate the synthesis of various perovskite-based hybrid materials and their further optoelectronic applications.

13.
Sci Immunol ; 4(37)2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300478

RESUMO

Immunological tolerance of tumors is characterized by insufficient infiltration of cytotoxic T lymphocytes (CTLs) and immunosuppressive microenvironment of tumor. Tumor resistance to immune checkpoint inhibitors due to immunological tolerance is an ongoing challenge for current immune checkpoint blockade (ICB) therapy. Here, we report the development of tumor microenvironment-activatable anti-PDL1 antibody (αPDL1) nanoparticles for combination immunotherapy designed to overcome immunological tolerance of tumors. Combination of αPDL1 nanoparticle treatment with near-infrared (NIR) laser irradiation-triggered activation of photosensitizer indocyanine green induces the generation of reactive oxygen species, which promotes the intratumoral infiltration of CTLs and sensitizes the tumors to PDL1 blockade therapy. We showed that the combination of antibody nanoparticles and NIR laser irradiation effectively suppressed tumor growth and metastasis to the lung and lymph nodes in mouse models. The nanoplatform that uses the antibody nanoparticle alone both for immune stimulation and PDL1 inhibition could be readily adapted to other immune checkpoint inhibitors for improved ICB therapy.

14.
Emerg Infect Dis ; 25(10)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31264568

RESUMO

We estimated the incubation period and serial interval for human-to-human-transmitted avian influenza A(H7N9) virus infection using case-patient clusters from epidemics in China during 2013-2017. The median incubation period was 4 days and serial interval 9 days. China's 10-day monitoring period for close contacts of case-patients should detect most secondary infections.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31268350

RESUMO

Osteoporosis (OP) is common with advancing age. Several studies have shown a strong correlation between OP and otosclerosis. However, no studies have investigated OP of the malleus, incus or stapes in the human middle ear, its effect on middle ear transfer function. Here, we investigate whether these three ossicles develop OP, and how this affects middle ear transfer function. The effect of OP on middle ear transfer function was investigated in simulations based on a finite element (FE) method. First, the FE model used in our previous study was refined, and optimized by introducing viscoelastic properties to selected soft tissues of the middle ear. Then, the FE model was used to simulate OP of the three ossicles and assess its influence on middle ear transfer function. Other possible age-related changes, such as stiffness of the joints or ligaments in the middle ear, were also investigated. The results indicated that OP of the ossicles could increase the high frequency displacement of both the umbo and stapes footplate (FP). However, the stiffness of the middle ear soft tissue can lead to the decrease of middle ear gain at lower frequencies. Furthermore, loosening of these joints or ligaments could increase displacement of the umbo and stapes FP. In conclusion, although age-related hearing loss is most commonly conceived of as sensorineural hearing loss (SNHL), we found that age-related changes may also include OP and changes in joint stiffness, but these will have little effect on middle ear transfer function in elderly people.

16.
Sci Total Environ ; 692: 201-208, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31344571

RESUMO

The widespread occurrence of sulfonamides (SAs) in natural waters, wastewater, soil and sediment has raised increasing concerns about their potential risks to human health and ecological systems. Sulfate radical (SO4-)-based advanced oxidation processes (SR-AOPs) have become promising technologies to remove such contaminants in the environment. The present study systematically investigated the degradation of four selected SAs with different five-membered heterocyclic rings, namely, sulfamethoxazole (SMX), sulfisoxazole (SIX), sulfathiazole (STZ), and sulfamethizole (SMT), by thermo-activated persulfate (PS) process, and the role of heterocyclic rings was assessed particularly. The results revealed that all the selected SAs could be degraded efficiently by thermo-activated PS process and their decay rates were appreciably increased with increasing temperature. For instance, degradation rates of STZ increased from 0.3 × 10-3 to 19.5 × 10-3 min-1 as the temperature was increased from 30 to 60 °C. Under the same experimental conditions, the degradation rates of SAs followed the order of SIX > SMX ≈ STZ > SMT, which was in accordance with decay rates of their R-NH2 moieties. Kinetic results indicated that five-membered heterocyclic rings could serve as reactive moieties toward SO4- attack, which were confirmed by frontier electron density (FED) calculations. Based on the transformation products identified by high-resolution mass spectrometry (HR-MS), five different oxidation pathways, including hydroxylation, aniline moiety oxidation, dimerization, sulfonamide bond cleavage, and heterocyclic ring oxidation/cleavage were proposed. Moreover, the degradation efficiency in real surface water (RSW) was found to be slightly slower than that in artificial surface water (ASW), suggesting that SR-AOPs could be an efficient approach for remediation of soil and water contaminated by these SAs.

17.
J Mater Sci Mater Med ; 30(8): 87, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31325047

RESUMO

Previous studies have demonstrated the significant roles of simvastatin (SVA) and oxysterols in the osteogenesis process. In this study, we evaluate the effect of a combination of SVA and 20(S)-hydroxycholesterol (20(S)OHC) on the cell viability and osteogenic differentiation of bone marrow stromal cells (BMSCs). After treatment with a control vehicle, SVA (0.025, 0.10, 0.25 or 1.0 µM), 20(S)OHC (5 µM), or a combination of both (0.25 µM SVA + 5 µM 20(S)OHC), the proliferation, apoptosis, ALP activity, mineralization, osteogenesis-related gene expression and Raf/MEK/ERK signaling activity in BMSCs were measured. Our results showed that high concentrations of SVA (0.25 and 1.0 µM) enhanced osteogenesis-related genes expression while attenuating cell viability. The addition of 5 µM 20(S)OHC induced significantly higher proliferative activity, which neutralized the inhibitory effect of SVA on the viability of BMSCs. Moreover, compared to supplementation with only one of the additives, combined supplementation with both SVA and 20(S)OHC induced significantly enhanced ALP activity, calcium sedimentation, osteogenesis-related genes (ALP, OCN and BMP-2) expression and Raf/MEK/ERK signaling activity in BMSCs; these enhancements were attenuated by treatment with the inhibitor U0126, indicating a significant role of Raf/MEK/ERK signaling in mediating the synergistically enhanced osteogenic differentiation of BMSCs by combined SVA and 20(S)OHC treatment. Additionally, histological examination confirmed a synergistic effect of SVA and 20(S)OHC on enhancing bone regeneration in a rabbit calvarial defect model. This newly developed SVA/20(S)OHC formulation may be used as an osteoinductive drug to enhance bone healing.

18.
Virol Sin ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31347089

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is characterized by its genetic variation and limited cross protection among heterologous strains. Even though several viral structural proteins have been regarded as inducers of neutralizing antibodies (NAs) against PRRSV, the mechanism underlying limited cross-neutralization among heterologous strains is still controversial. In the present study, examinations of NA cross reaction between a highly pathogenic PRRSV (HP-PRRSV) strain, JXwn06, and a low pathogenic PRRSV (LP-PRRSV) strain, HB-1/3.9, were conducted with viral neutralization assays in MARC-145 cells. None of the JXwn06-hyperimmuned pigs' sera could neutralize HB-1/3.9 in vitro and vice versa. To address the genetic variation between these two viruses that are associated with limited cross-neutralization, chimeric viruses with coding regions swapped between these two strains were constructed. Viral neutralization assays indicated that variations in nonstructural protein 2 (nsp2) and structural proteins together contribute to weak cross-neutralization activity between JXwn06 and HB-1/3.9. Furthermore, we substituted the nsp2-, glycoprotein2 (GP2)-, GP3-, and GP4-coding regions together, or nsp2-, GP5-, and membrane (M) protein-coding regions simultaneously between these two viruses to construct chimeric viruses to test cross-neutralization reactivity with hyperimmunized sera induced by their parental viruses. The results indicated that the swapped nsp2 and GP5-M viruses increased the neutralization reactivity with the donor strain antisera in MARC-145 cells. Taken together, these results show that variations in nsp2 and GP5-M correlate with the limited neutralization reactivity between the heterologous strains HP-PRRSV JXwn06 and LP-PRRSV HB-1/3.9.

19.
Cancer Med ; 8(11): 5148-5157, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347292

RESUMO

PURPOSE: Notch signaling dysregulation is implicated in the development of pancreatic adenocarcinoma (PDAC). Tarextumab is a fully human IgG2 antibody that inhibits Notch2/3 receptors. PATIENTS AND METHODS: Aphase 2, randomized, placebo-controlled, multicenter trial evaluated the activity of tarextumab in combination with nab-paclitaxel and gemcitabine in patients with metastatic PDAC. Patients were stratified based on ECOG performance score and Ca 19-9 level and randomized 1:1 to nab-paclitaxel, gemcitabine with either tarextumab or placebo. Based on preclinical and phase Ib results suggesting a positive correlation between Notch3 gene expression and tarextumab anti-tumor activity, patients were also divided into subgroups of low, intermediate, and high Notch3 gene expression. Primary endpoint was overall survival (OS) in all and in patients with the three Notch3 gene expression subgroups (≥25th, ≥50% and ≥75% percentiles); secondary end points included progression-free survival (PFS), 12-month OS, overall response rate (ORR), and safety and biomarker investigation. RESULTS: Median OS was 6.4 months in the tarextumab group vs 7.9 months in the placebo group (HR = 1.34 [95% CI = 0.95, 1.89], P = .0985). No difference observed in OS in the Notch3 gene expression subgroups. PFS in the tarextumab-treated group (3.7 months) was significantly shorter compared with the placebo group (5.5 months) (hazard ratio was 1.43 [95% CI = 1.01, 2.01]; P = .04). Grade 3 diarrhea and thrombocytopenia were more common in the tarextumab group. CONCLUSIONS: The addition of tarextumab to nab-paclitaxel and gemcitabine did not improve OS, PFS, or ORR in first-line metastatic PDAC, and PFS was specifically statistically worse in the tarextumab-treated patients. CLINICAL TRIAL REGISTRY NO: NCT01647828.

20.
Epigenomics ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31290331

RESUMO

Aim: To assess the m6A methylome in mouse fatty liver induced by a high-fat diet (HFD). Materials & methods: MeRIP-seq was performed to identify differences in the m6A methylomes between the normal liver and fatty liver induced by an HFD. Results: As compared with the control group, the upmethylated coding genes upon feeding an HFD were primarily enriched in processes associated with lipid metabolism, while genes with downmethylation were enriched in processes associated with metabolism and translation. Furthermore, many RNA-binding proteins that potentially bind to differentially methylated m6A sites were mainly annotated in processes of RNA splicing. Conclusion: These findings suggest that differential m6A methylation may act on functional genes through RNA-binding proteins to regulate the metabolism of lipids in fatty liver disease.

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