Pigs are considered as important hosts or “mixing vessels” for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.
Postmenopausal osteoporosis induced by estrogen deficiency causes inadequate new bone formation and affects millions of women worldwide. Melatonin can improve bone mineral density at the femoral neck in postmenopausal women with osteopenia. This study aimed to investigate the mechanism of melatonin in estrogen deficiency-induced osteoporosis by focusing on osteoblast differentiation. 12-week-old female C57BL/6J mice were ovariectomized (OVX) and intraperitoneally injected with 10 or 50 mg/kg of melatonin for 8 weeks. Micro-computerized tomography scanning demonstrated that melatonin alleviated OVX-induced bone loss in a dose-dependent manner. Serum levels of ALP and osteocalcin (OCN) were further increased, whereas tartrate-resistant acid phosphatase level was decreased by melatonin in OVX-treated mice. Melatonin promoted osteoblast differentiation in primary bone marrow mesenchymal stem cells from OVX mice. It also inhibited activation of NLRP3 inflammasome in femoral bone protein and in induced osteoblasts stimulated by OVX. Knockdown of NLRP3 attenuated OVX-induced repression of osteogenic differentiation. The NLRP3 inflammasome activator monosodium urate partly abrogated the effect of melatonin on the expression of osteoblastogenic markers, including Runx2 and OCN. Additionally, the results showed that melatonin suppressed NLRP3 inflammasome activation by regulating Wnt/β-catenin signaling, which was confirmed by the Wnt/β-catenin inhibitor recombinant DKK1. These results indicated that melatonin ameliorates estrogen deficiency-induced osteoporosis and impaired osteogenic differentiation potential by suppressing activation of the NLRP3 inflammasome via mediating the Wnt/β-catenin pathway.
Due to an altered expression of oncogenic factors and tumor suppressors, aggressive cancer cells have an intrinsic or acquired resistance to chemotherapeutic agents. This typically contributes to cancer recurrence after chemotherapy. microRNAs are short non-coding RNAs that are involved in both cell self-renewal and cancer development. Here we report that tumor cells transfected with miR-378 acquired properties of aggressive cancer cells. Overexpression of miR-378 enhanced both cell survival and colony formation, and contributed to multiple drug resistance. Higher concentrations of chemotherapeutic drugs were needed to induce death of miR-378-transfected cells than to induce death of control cells. We found that the biologically active component isolated from Ganoderma lucidum could overcome the drug-resistance conferred by miR-378. We purified and identified the biologically active component of Ganoderma lucidum as ergosterol peroxide. We demonstrated that ergosterol peroxide produced greater activity in inducing death of miR-378 cells than the GFP cells. Lower concentrations of ergosterol peroxide were needed to induce death of the miR-378-transfected cells than in the control cells. With further clinical development, ergosterol peroxide represents a promising new reagent that can overcome the drug-resistance of tumor cells.
The current study was to better understand the potential factors affecting aflatoxin B1 (AFB1) accumulation varies between different grains. The nutrient composition and contents of defatted substrates were determined; additionally, according to the nutrient content of the substrates, the effects of starch, soluble sugars, amino acids, and trace elements on AFB1 production and mycelial growth in Czapek-Dox medium were examined. These results verified that removal of lipids from ground substrates significantly reduced the substrate's potential for AFB1 production by Aspergillus flavus. Maltose, glucose, sucrose, arginine, glutamic acid, aspartic acid, and zinc significantly induced AFB1 production up to 1.7- to 26.6-fold. And stachyose more significantly promoted A. flavus growth than the other nutrients. Thus, this study demonstrated that, combined with the nutrients content of grains, in addition to lipids, sucrose, stachyose, glutamic acid, and zinc might play key roles in various grains that are differentially infected by A. flavus. Particularly, two new nutrients (arginine and stachyose) of the grains we found significantly stimulate AFB1 production and A. flavus growth, respectively. The results provide new concepts for antifungal methods to protect food and animal feed from AFB1 contamination.
Selenium (Se) is an essential trace element for animal and human. Supplementation of Se usually in livestock diet has been proved as effective element. This study was conducted to investigate the effect of different sources of selenium on growth performance, slaughter performance, immune trait, oxidation resistance, meat quality and selenium content in tissue of broilers to comprehensively evaluate the effect of selenium. A total of 324 1-day-old AA broilers were selected and randomly allocated to three treatments of six replicates with 18 broilers each. The trial period was 42 days and was divided into two periods. Our results showed that effect of different sources of selenium on growth performance, slaughter performance, the immune status, drip loss and flesh had not significant difference (p > 0.05); while the activities of serum glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), the abilities to inhibit hydroxyl radical (OH˙) and total antioxidant capacity (T-AOC) were significantly higher in selenium yeast than sodium selenite groups, and the contents of MDA of selenium yeast groups were significantly lower than that of sodium selenite. This study demonstrated that the different sources of selenium had no obvious effect on production performance of broilers, but significantly influenced the broiler oxidation resistance.
BackgroundInitial therapy for patients with acute promyelocytic leukemia most often involves the combination of all-trans-retinoic acid with anthracycline-based chemotherapy. The role of nonanthracycline drugs in induction and consolidation is less well-established and varies widely between different cooperative group protocols. Design and MethodsIn an attempt to minimize relapse and maximize survival for patients with newly diagnosed acute promyelocytic leukemia, the Australasian Leukaemia and Lymphoma Group utilized alltrans-retinoic acid and idarubicin as anti-leukemic therapy for both induction and consolidation. The protocol (known as APML3) was subsequently amended to incorporate maintenance with all-trans-retinoic acid, methotrexate and 6-mercaptopurine. ResultsEight (8%) of 101 patients died within 30 days, and 91 (90%) achieved complete remission. With a median estimated potential follow-up of 4.6 years, 4-year overall survival was 84%, and 71% of the patients remained in remission at 4 years. The cumulative incidence of all relapses was 28.1%, with 15 of the 25 relapses initially identified as an isolated molecular relapse. Both FLT3 mutations (internal tandem duplications and codon 835/836 kinase domain mutations) and increased white cell count at diagnosis were associated with inferior overall survival, but in multivariate analyses only FLT3 mutations remained significant (hazard ratio 6.647, P=0.005). Maintenance therapy was significantly associated with improved remission duration (hazard ratio 0.281, P<0.001) and disease-free survival (hazard ratio 0.290, P<0.001). ConclusionsThe combination of all-trans-retinoic acid and just two cycles of idarubicin followed by triple maintenance produced durable remissions in most patients, but patients with high-risk disease, especially those with FLT3 mutations, require additional agents or alternative treatment approaches. The significant reduction in relapse seen after the addition of maintenance to the protocol supports a role for maintenance in the context of relatively low chemotherapy exposure during consolidation. 2012;97(2):227-234. doi:10.3324/haematol.2011 This is an open-access paper. Results of the APML3 trial incorporating all-trans-retinoic acid and idarubicin in both induction and consolidation as initial therapy for patients with acute promyelocytic leukemia. Haematologica Results of the APML3 trial incorporating all-trans-retinoic acid and idarubicin in both induction and consolidation as initial therapy for patients with acute promyelocytic leukemia
Axillary lymph node metastasis was prone to happen in patients with US features of an irregular tumor shape and higher color Doppler flow imaging grades. Ultrasound imaging provides a promising tool for predicting axillary lymph node metastasis in patients with breast cancer.
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