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1.
PLoS One ; 16(10): e0257505, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34597300

RESUMEN

In this paper, we assume that the supply chain for new energy vehicles (NEVs) consists of a manufacturer and N parts suppliers, considering that the R&D investment of both manufacturer and suppliers will affect the market demand of NEVs and NEVs credit, we construct decentralized and centralized decision-making models under the dual-credit policy to study the R&D investment strategy of supply chain enterprises. Furthermore, considering that suppliers can form alliances, we establish bargaining game models under the conditions of the non-alliance and alliance of suppliers, and discuss the coordination strategy for the NEVs supply chain. It is found that, under the dual-credit policy, the higher the credit coefficient of technology improvement, the higher the transaction price of credits, and the higher the R&D investment of supply chain. Dual-credit policy can effectively encourage NEVs supply chain to increase R&D investment, improve NEV technology level, and improve the profit of supply chain. Under the dual-credit policy, the increment profit distribution strategy based on a bargaining game model can coordinate the NEVs supply chain. When suppliers separately negotiate with the manufacturer, bringing the negotiation sequence forward, the supplier can get more profits. However, as the manufacturer has the right to determine the negotiation sequence, the supplier can only get the profit of the last round of negotiation, and the manufacturer can get excess profit. Forming a suppliers alliance can solve this problem effectively, and increase the profit of all suppliers when the alliance`s negotiating power is improved to a certain threshold.

2.
Biosci Rep ; 41(10)2021 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-34633445

RESUMEN

To clarify the effect of retinoid X receptor-α/γ (RXR-α/γ) genes functional genetic variants (RXR-α rs4842194 G>A, RXR-γ rs100537 A>G and rs2134095 T>C) on the risk of gestational diabetes mellitus (GDM), a case-control study with 573 GDM patients and 740 pregnant women with normal glucose tolerance was performed in Guangxi area of China. An odds ratio (OR) with its corresponding 95% confidence interval (CI) was used to assess the strengths of the association between genetic variation and GDM. After adjustment of age and pre-BMI, the logistic regression analysis showed that the rs2134095 was significantly associated with GDM risk (CC vs. TT/TC: adjusted OR = 0.71, 95% CI = 0.56-0.90) in all subjects, and this result remained highly significant after Bonferroni's correction for multiple testing (P=0.004). The stratified analysis showed that rs2134095 was significantly associated with the risk of GDM among age > 30 years (adjusted OR = 0.61, 95% CI = 0.39-0.97), BMI > 22 kg/m2 (adjusted OR = 0.46, 95% CI = 0.30-0.70), systolic blood pressure (SBP) > 120 mmHg (adjusted OR = 1.96, 95% CI = 1.14-3.36), glycosylated hemoglobin A1c (HbA1c) < 6.5% (adjusted OR = 1.41, 95% CI = 1.11-1.78), TG ≤ 1.7 mmol/l (adjusted OR = 2.57, 95% CI = 1.45-4.53), TC ≤ 5.18 mmol/l (adjusted OR = 1.58, 95% CI = 1.13-2.22), high-density lipoprotein cholesterol (HDL-c) ≤ 1.5 mmol/l (adjusted OR = 1.70, 95% CI = 1.16-2.49) and low-density lipoprotein cholesterol (LDL-c) > 3.12 mmol/l (adjusted OR = 1.47, 95% CI = 1.08-2.00) subjects, under the recessive genetic model. We also found that rs2134095 interacted with age (Pinteraction=0.039), pre-BMI (Pinteraction=0.040) and TG (Pinteraction=0.025) influencing individual's genetic susceptibility to GDM. The rs2134095 T>C is significantly associated with the risk of GDM by effect of a single locus and/or complex joint gene-gene and gene-environment interactions. Larger sample-size and different population studies are required to confirm the findings.

3.
Int J Epidemiol ; 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34632511

RESUMEN

BACKGROUND: Exercise may increase the inhalation and deposition of air pollutants, which may counteract its beneficial effects. We thus examined the combined effects of chronic exposure to fine particulate matter (PM2.5) and habitual exercise on the risk of death from cancer in Taiwan. PATIENTS AND METHODS: A total of 384 128 adults (≥18 years of age) were recruited for a medical screening programme between 2001 and 2016, yielding 842 384 medical-examination records. All participants were followed up until 31 May 2019. Vital data were obtained from the National Death Registry of Taiwan and the ambient PM2.5 exposure was estimated using a satellite-based spatiotemporal model. Information on habitual exercise was collected using a standard self-administered questionnaire. The time-dependent Cox-regression model was used to evaluate the combined effects. RESULTS: A greater amount of habitual exercise was associated with lower risk of death from cancer, whilst a higher level of PM2.5 exposure was associated with a higher risk of death from cancer. The inverse associations of habitual exercise with death from cancer were not modified by chronic exposure to PM2.5. The participants in the group with a high level of exercise and a low level of PM2.5 exposure exhibited a 35% lower risk of death from cancer than those in the group with a low level of exercise and a high level of PM2.5 exposure (95% confidence interval: 28%, 42%). CONCLUSIONS: Increased levels of exercise and reduced exposure levels of PM2.5 are associated with a lower risk of death from cancer. Habitual exercise reduces the risk of death from cancer regardless of the levels of chronic PM2.5 exposure. Our results indicate that habitual exercise is a suitable health-promotion strategy even for people who reside in moderately polluted regions.

4.
Materials (Basel) ; 14(19)2021 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-34640018

RESUMEN

Optimizing the mechanical properties of composites through microstructural design has been a long-standing issue in materials science. In this study, we reinforced a typical polymer, i.e., polyethylene-terephthalate-woven fabric, with a type of Fe-based metallic glassy fiber (MGF) with an extremely large Young's moduli. The MGF-reinforced fabrics, with three different fiber bundle orientations (0°, 45°, and 90°), were investigated by in situ electron-microscopy mechanical testing techniques in conjunction with a digital image correlation (DIC) technique. The fabrics exhibited a pronounced anisotropic mechanical response, and the associated characteristics were verified to depend on the fiber bundle orientation relative to the external load. Furthermore, localized strains near the intersections of the fiber bundles were found to be much higher than the global strain. It is confirmed that the restriction from warp to weft is the dominant factor influencing strain localization during deformation. Our results are enlightening for understanding the fracture mechanisms of composites.

5.
Oxid Med Cell Longev ; 2021: 8542809, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34650665

RESUMEN

Patients with metabolic syndrome have a higher risk of type II diabetes and cardiovascular disease. The metabolic syndrome has become an urgent public health problem. Insulin resistance is the common pathophysiological basis of metabolic syndrome. The higher incidence of insulin resistance in obese groups is due to increased levels of inflammatory factors during obesity. Therefore, developing a therapeutic strategy for insulin resistance has great significance for the treatment of the metabolic syndrome. Dihydromyricetin, as a bioactive polyphenol, has been used for anti-inflammatory, antitumor, and improving insulin sensitivity. However, the target of DHM and molecular mechanism of DHM for preventing inflammation-induced insulin resistance is still unclear. In this study, we first confirmed the role of dihydromyricetin in inflammation-induced insulin resistance in vivo and in vitro. Then, we demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance by activating Ca2+-CaMKK-AMPK using signal pathway blockers, Ca2+ probes, and immunofluorescence. Finally, we clarified that dihydromyricetin activated Ca2+-CaMKK-AMPK signaling pathway by interacting with the phospholipase C (PLC), its target protein, using drug affinity responsive target stability (DARTS) assay. Our results not only demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance via the PLC-CaMKK-AMPK signal pathway but also discovered that the target protein of dihydromyricetin is the PLC. Our results provided experimental data for the development of dihydromyricetin as a functional food and new therapeutic strategies for treating or preventing PLC.

6.
Front Med (Lausanne) ; 8: 690528, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34604250

RESUMEN

Purpose: To investigate the incidence, characteristics, and risk factors of sports-related eye injuries among athletes in Tianjin, China. Methods: A cross-sectional study was carried out from March 2018 to October 2018. In this study, the athletes from Tianjin University of Sports, Tianjin Vocational College of Sports, and Tianjin provincial sports teams were selected for general investigation. In total, 1,673 athletes were invited and 1,413 participated in the study (response rate of 84.5%). Results: In total, 1,413 athletes were enrolled; 151 had suffered from sports-related eye injuries, with an incidence of 10.7% (95% CI: 9.1-12.0%). Handball (38.5%) was the sport with the highest incidence of eye injuries, followed by water polo (36.4%) and diving (26.7%). Overall, 42.4% of the athletes were injured by ball and 22.5% of injuries came from teammates. The eye injuries usually occurred during training (64.2%) and competitions (14.6%). Adnexa wound (51.7%) was the most common type of injury. About 11.9% of the athletes with eye injuries had the impaired vision; 66.7% failed to see doctors on time. The athletes <18 years of age had a higher risk of eye injuries (odds ratio [OR] =1.60, 95% CI: 1.06-2.40). The athletes with lower family income (<1,000 RMB) were at risk population for sports-related eye injuries (OR = 3.91, 95% CI: 2.24-6.82). Training >4 h a day increased the risk of eye injuries (OR = 2.21, 95% CI: 1.42-3.43). Conclusion: The incidence of sports-related eye injuries among athletes was 10.7% in Tianjin, China. Handball, water polo, and diving were the most common activities of injury. Age, family income, and training time were the risk factors for sports-related eye injuries.

7.
Cancer Lett ; 523: 182-194, 2021 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-34627950

RESUMEN

Rab1A overexpression has been observed in several cancer types, however, its significance and the underlying mechanisms in non-small cell lung cancer (NSCLC) remain largely unexplored. This study demonstrated that Rab1A overexpression in NSCLC was significantly correlated to short survival and metastasis. Rab1A overexpression promoted cancer cell migration, invasion, and metastasis both in vitro and in vivo, by activating JAK1/STAT6 signaling through stabilizing IL-4Rα protein. Strikingly, high Rab1A level was associated with sensitivity to JAK1 inhibitor, and Rab1A overexpression rendered cancer cells vulnerable to JAK1-targeted agents. JAK1 inhibitor, Itacitinib adipate, dramatically inhibited high Rab1A NSCLC metastasis, in both cell line and patient derived xenograft models. Collectively, these findings demonstrated that Rab1A plays a critical role in the aggressive properties of NSCLC, revealing a unique mechanism by which it promotes metastasis. In addition, we found that Rab1A is a determinant of JAK1 inhibitor sensitivity, which could be explored for improving JAK1-targeted cancer therapy.

8.
Opt Express ; 29(18): 28406-28415, 2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34614972

RESUMEN

Deep neural networks (DNNs) have been used as a new method for nanophotonic inverse design. However, DNNs need a huge dataset to train if we need to select materials from the material library for the inverse design. This puts the DNN method into a dilemma of poor performance with a small training dataset or loss of the advantage of short design time, for collecting a large amount of data is time consuming. In this work, we propose a multi-scenario training method for the DNN model using imbalanced datasets. The imbalanced datasets used by our method is nearly four times smaller compared with other training methods. We believe that as the material library increases, the advantages of the imbalanced datasets will become more obvious. Using the high-precision predictive DNN model obtained by this new method, different multilayer nanoparticles and multilayer nanofilms have been designed with a hybrid optimization algorithm combining genetic algorithm and gradient descent optimization algorithm. The advantage of our method is that it can freely select discrete materials from the material library and simultaneously find the inverse design of discrete material type and continuous structural parameters of the nanophotonic devices.

9.
Target Oncol ; 2021 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-34687398

RESUMEN

BACKGROUND: Relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis despite the availability of multiple treatment options. Preliminary evidence suggests that DLBCL may be responsive to programmed death ligand 1 (PD-L1)/programmed death 1 inhibitors. OBJECTIVE: The JAVELIN DLBCL study was conducted to assess whether a combination of agents could augment and sustain the antitumor immunity of avelumab, an anti-PD-L1 antibody, in R/R DLBCL. METHODS: This was a multicenter, randomized, open-label, parallel-arm study with a phase Ib and a phase III component. Reported here are the results from the phase Ib study, wherein 29 adult patients with DLBCL were randomized 1:1:1 to receive avelumab in combination with utomilumab (an immunoglobulin G2 4-1BB agonist) and rituximab (arm A), avelumab in combination with utomilumab and azacitidine (arm B), or avelumab in combination with bendamustine and rituximab (arm C). The primary endpoints were dose-limiting toxicities and objective response as assessed by the investigator per Lugano Response Classification criteria. RESULTS: Of the seven patients in arm A, one (14.3%) experienced two grade 3 dose-limiting toxicities (herpes zoster and ophthalmic herpes zoster); no dose-limiting toxicities were reported in arms B or C. No new safety concerns emerged for avelumab. One partial response was reported in arm A, three complete responses in arm C, and no responses in arm B. Given the insufficient antitumor activity in arms A and B and the infeasibility of expanding arm C, the study was discontinued before initiation of the phase III component. CONCLUSIONS: The low level of clinical activity suggests that PD-L1 inhibitor activity may be limited in R/R DLBCL. CLINICALTRIALS. GOV IDENTIFIER: NCT02951156.

10.
Q J Exp Psychol (Hove) ; : 17470218211052502, 2021 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-34609217

RESUMEN

Visual working memory (VWM) is responsible for the temporal retention and manipulation of visual information. It has been suggested that VWM employs an object-based encoding (OBE) manner to extract highly discriminable information from visual perception: Whenever one feature dimension of the objects is selected for entry into VWM, the other task-irrelevant highly discriminable dimension is also extracted into VWM involuntarily. However, the task-irrelevant feature in OBE studies might reflect a high capacity fragile VWM (FVWM) trace that stores maskable sensory representations. To directly compare the VWM storage hypothesis and the FVWM storage hypothesis, we used a unique characteristic of FVWM that the representations in FVWM could be erased by backward masks presented at the original locations of the memory array. We required participants to memorise the orientations of three coloured bars while ignoring their colours, and presented backward masks during the VWM maintenance interval. In four experiments, we consistently observed that the OBE occurs regardless of the presentation of the backward masks, except when even the task-relevant features in VWM were significantly interrupted by immediate backward masks, suggesting that the task-irrelevant features of objects are stored in VWM rather than in FVWM.

11.
Healthcare (Basel) ; 9(10)2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34682973

RESUMEN

The ongoing spread of coronavirus disease 2019 (COVID-19) in most South and Southeast Asian countries has led to severe health and economic impacts. Evaluating the performance of nonpharmaceutical interventions in reducing the number of daily new cases is essential for policy designs. Analysis of the growth rate of daily new cases indicates that the value (5.47%) decreased significantly after nonpharmaceutical interventions were adopted (1.85%). Vaccinations failed to significantly reduce the growth rates, which were 0.67% before vaccination and 2.44% and 2.05% after 14 and 28 d of vaccination, respectively. Stringent nonpharmaceutical interventions have been loosened after vaccination drives in most countries. To predict the spread of COVID-19 and clarify the implications to adjust nonpharmaceutical interventions, we build a susceptible-infected-recovered-vaccinated (SIRV) model with a nonpharmaceutical intervention module and Metropolis-Hastings sampling in three scenarios (optimistic, neutral, and pessimistic). The daily new cases are expected to decrease rapidly or increase with a flatter curve with stronger nonpharmaceutical interventions, and the peak date is expected to occur earlier (5-20 d) with minimum infections. These findings demonstrate that adopting stringent nonpharmaceutical interventions is the key to alleviating the spread of COVID-19 before attaining worldwide herd immunity.

12.
Front Plant Sci ; 12: 752584, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34691129

RESUMEN

Land plants live in a crisis-filled environment and the fluctuation of sunlight intensity often causes damage to photosynthetic apparatus. Phyto-melatonin is an effective bioactive molecule that helps plants to resist various biotic and abiotic stresses. In order to explore the role of melatonin under high light stress, we investigated the effects of melatonin on anti-oxidative system and photosynthesis of Arabidopsis thaliana under high light. Results showed that exogenous melatonin increased photosynthetic rate and protected photosynthetic proteins under high light. This was mainly owing to the fact that exogenous melatonin effectively decreased the accumulation of reactive oxygen species and protected integrity of membrane and photosynthetic pigments, and reduced cell death. Taken together, our study promoted more comprehensive understanding in the protective effects of exogenous melatonin under high light.

13.
Sci Total Environ ; 792: 148329, 2021 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-34465047

RESUMEN

The emission factor (EF), the weight of potentially toxic elements (PTEs) per unit energy or weight of sinter produced were evaluated for coal-fired boilers and sintering furnaces integrated in a steel plant. From three coal-fired boilers, 15 samples were taken while 22 samples were taken from four sintering furnaces. Investigations were performed on the EF of lead, cadmium, mercury, arsenic and chromium (VI). The coefficient of variance for the first 3 samples from each PTE was used to decide whether 2 more samples were necessary for the investigation. Three samples were sufficient for Cr (VI), however, 5 samples were required for Pb, Cd, Hg, and As, since the variances in concentrations of the first three samples exceeded 20%. The ranges for the ratio of the laboratory-based EF to the default EF applied by the Environment Protection Administration (EPA Taiwan) for Pb, Cd, Hg, and As for the coal-fired boiler were 0.08-0.013, 0.014-0.017, 0.019-0.033, 0.047-0.066 and for the sintering furnaces were 0.059-0.232, 0.05-0.151, 0.05-0.364, and 0.067-0.824. The ratio for Cr (VI)- was constant at 0.005 for all the coal fired boilers while it ranged from 0.057-0.709 for the sintering furnaces. Whilst source identification, enrichment factors, and spatial distributions for PTEs are often studied, laboratory-based investigations on the EFs for PTEs from industrial plants are rarely performed. This study filled the information gap and compared the obtained EFs with the EPA default values. To avoid overcharging industrial plants equipped with the best available technology for emission control, the EPA should apply field investigations and laboratory-based EFs instead of the default EPA EFs to calculate air pollution fees. Insights from this investigation can be applied to promote the adoption of appropriate air pollution control devices to cut down the emission of PTEs.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Mercurio , Contaminantes Atmosféricos/análisis , Carbón Mineral/análisis , Centrales Eléctricas , Acero
14.
Carbohydr Polym ; 273: 118560, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34560971

RESUMEN

The film-forming process of chitosan composite films is an important issue because it affects their experimental design, chemicals used, and feasibility of large-scaled fabrication. In this work, electrophoresis is employed to produce chitosan composite films with significantly reduced processing time and environmentally friendly chemicals. With the addition of hydrogen peroxide and polyethylene glycol, the parasitic hydrogen bubble formation during the electrophoresis of chitosan and polydopamine is effectively inhibited that leads to the formation of a defectless chitosan/polyethylene glycol/polydopamine composite film which could be removed from the substrate readily. In addition, the chitosan/polyethylene glycol/polydopamine composite film reveals significantly improved tensile strength and a slower decomposition rate as compared to those of chitosan film and chitosan/polyethylene glycol composite film. This is attributed to the strong interaction between chitosan and polydopamine. Lastly, the chitosan/polyethylene glycol/polydopamine composite film exhibits excellent UV-shielding ability without compromising its visible transparency.

15.
J Fungi (Basel) ; 7(9)2021 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-34575775

RESUMEN

Ketol-acid reductoisomerase (ILVC) is the second enzyme in the branched-chain amino acid (BCAA) biosynthesis, which regulates many physiological activities in a variety of organisms from bacteria to fungi and plants. In this work, function mechanisms of ILVC in Metarhizium robertsii Metchnikoff (Hypocreales: Clavicipitaceae) were explored with site-directed mutagenesis, reductase activity assays and transcriptomics analysis. The reductase activity assays showed that ILVC from phytopathogenic fungi exhibited significantly higher activities than those from entomopathogenic fungi but lower than those from yeast. Site-directed mutagenesis and enzymatic activities of MrILVC with different active-site mutants (Arg-113, Ser-118, Asp-152, Asp-260, and Glu-264) confirmed that active sites of MrILVC are conserved with plant and bacterial ILVCs. Deleting MrilvC causes the complete failures of vegetative growth and conidial germination, feeding with branched-chain amino acids (BCAAs) recovers the fungal growth but not conidial germination, while both characteristics are restored when supplemented with yeast extract. Compared to ΔMrilvC cultured in czapek agar (CZA), plenty of genes involved in the biosynthesis of antibiotics and amino acids were up- or down-regulated in the wild type or ΔMrilvC feeding with either BCAAs or yeast extract. Further analysis showed some genes, such as catalase A, participate in mycelial growth and conidial germination was down-regulated in ΔMrilvC from CZA, revealing that MrILVC might control the fungal development by gene regulation and BCAAs or yeast extract could play partial roles of MrILVC. This study will advance our understanding of ILVC function mechanisms in fungi.

16.
Polymers (Basel) ; 13(18)2021 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-34578089

RESUMEN

In this work, the development and application of multicomponents obtained from recycled polyethylene terephthalate (r-PET) waste and monotropic liquid crystals as anticorrosion coatings are reported. The r-PET raw material was alcoholyzed and reproduced as a thermoplastic polyester elastomer (TPEE) with different amounts (n%, n = 0, 1, 3, and 5) of 1,6-hexanediamine (HDA). Then, a fluorine-containing liquid crystal (4-cyano-3-fluorophenyl 4-ethylbenzoate (4CFE)) was incorporated into the TPEE mixture via solvent blending to modify and enhance the water resistance. The adhesion behavior of the coating on glass and iron substrates was evaluated by cross-cut tests and immersion tests in aqueous NaCl. In the corrosion resistance measurements, all of the coating samples fabricated with 10 ± 1 mm thickness were less active toward electrochemical corrosion (PEF% > 99%) than the bare iron plate, indicating that our work provided better protection against corrosion of the iron plate.

17.
Chem Commun (Camb) ; 57(80): 10395-10398, 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-34542550

RESUMEN

A novel trimethylolethane (TME)-substituted polyoxovanadate (POV) was designed as a precursor to prepare ultrasmall vanadium carbide nanoparticles, which markedly promoted the hydrogen evolution reaction and oxygen evolution reaction of iridium (Ir)-based electrocatalysts. This work is the first example employing organic ligand-substituted POV as the precursor for metal carbide, and is also the first combination of Ir and vanadium carbide, providing new insights into the design of excellent electrocatalysts.

18.
Arch Virol ; 166(11): 3233-3237, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34535823

RESUMEN

The entomopathogenic fungus Beauveria bassiana is used worldwide for biological control of insects. Seven dsRNA segments were detected in a single B. bassiana strain, RCEF1446. High-throughput sequencing indicated the presence of three mycoviruses in RCEF1446. Two were identified as the known mycoviruses Beauveria bassiana victorivirus 1 and Beauveria bassiana polymycovirus 1, and the novel mycovirus was designated as "Beauveria bassiana bipartite mycovirus 1" (BbBV1). The complete sequence of the BbBV1 is described here. The mycovirus contains two dsRNA segments. The RNA 1 (dsRNA 4) of BbBV1 is 2,026 bp in length, encoding a RNA-dependent RNA polymerase (RdRp) (68.54 kDa), while the RNA 2 (dsRNA 6) is 1,810 bp in length, encoding a hypothetical protein (35.55 kDa) with unknown function. Moreover, the amino acid sequence of RdRp showed the highest sequence identity of 62.31% to Botryosphaeria dothidea bipartite mycovirus 1. Phylogenetic analysis based on RdRp sequences revealed that BbBV1 represents a distinct lineage of unassigned dsRNA mycoviruses infecting fungi.


Asunto(s)
Beauveria/virología , Virus ARN Bicatenario/genética , Virus Fúngicos/genética , Genoma Viral , Filogenia , Beauveria/patogenicidad , ARN Bicatenario , ARN Polimerasa Dependiente del ARN/genética , Proteínas Virales/genética
19.
Elife ; 102021 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-34550070

RESUMEN

Parkinson's disease (PD) is a common neurodegenerative disorder without effective disease-modifying therapeutics. Here, we establish a chemogenetic dopamine (DA) neuron ablation model in larval zebrafish with mitochondrial dysfunction and robustness suitable for high-content screening. We use this system to conduct an in vivo DA neuron imaging-based chemical screen and identify the Renin-Angiotensin-Aldosterone System (RAAS) inhibitors as significantly neuroprotective. Knockdown of the angiotensin receptor 1 (agtr1) in DA neurons reveals a cell-autonomous mechanism of neuroprotection. DA neuron-specific RNA-seq identifies mitochondrial pathway gene expression that is significantly restored by RAAS inhibitor treatment. The neuroprotective effect of RAAS inhibitors is further observed in a zebrafish Gaucher disease model and Drosophila pink1-deficient PD model. Finally, examination of clinical data reveals a significant effect of RAAS inhibitors in delaying PD progression. Our findings reveal the therapeutic potential and mechanisms of targeting the RAAS pathway for neuroprotection and demonstrate a salient approach that bridges basic science to translational medicine.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Antiparkinsonianos/farmacología , Neuronas Dopaminérgicas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Sistema Renina-Angiotensina/efectos de los fármacos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Animales Modificados Genéticamente , Antiparkinsonianos/uso terapéutico , Estudios de Casos y Controles , Bases de Datos Factuales , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/metabolismo , Proteínas de Drosophila/deficiencia , Proteínas de Drosophila/genética , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Enfermedad de Gaucher/tratamiento farmacológico , Enfermedad de Gaucher/genética , Enfermedad de Gaucher/metabolismo , Ensayos Analíticos de Alto Rendimiento , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Sistema Renina-Angiotensina/genética , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
20.
Am J Cancer Res ; 11(8): 3841-3856, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34522453

RESUMEN

Chemoresistance is a major cause of treatment failure in pancreatic cancer (PC). It has been demonstrated that epithelial-to-mesenchymal transition (EMT) is closely related to drug resistance in PC; however, the underlying mechanisms are not yet fully understood. Recently found evidence has suggested that nuclear-enriched abundant transcript 1 (NEAT1) is involved in the development of chemoresistance. However, the role and mechanism of NEAT1 in PC gemcitabine resistance remain unknown. In the present study, we first established two independent gemcitabine-resistant (GR) PC cell lines, PANC-1/GR and SW1990/GR. We found that GR cells displayed markedly enhanced migration and invasion abilities, decreased expression of E-cadherin, and upregulation of N-cadherin, Vimentin, Snail, ZEB1, and ZEB2. Our findings suggested that downregulation of NEAT1 enhanced the sensitivity of GR cells to gemcitabine by reversing the EMT process. Mechanistically, NEAT1 mediates ZEB2 mRNA expression through sponging miR-506-3p. Downregulation of NEAT1 can reverse the EMT process of GR PC cells by reducing the expression of ZEB2, thus enhancing the sensitivity of GR PC cells to gemcitabine. These findings were further confirmed in a nude mouse xenograft model. Taken together, downregulation of NEAT1 sensitized the GR PC cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis. These results provide the novel evidence for understanding the function and molecular mechanism of NEAT1, and a new direction for improving the chemotherapeutic effects in PC.

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