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1.
Plant Physiol ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38850036

RESUMO

Water transportation to developing tissues relies on the structure and function of plant xylem cells. Plant microtubules govern the direction of cellulose microfibrils and guide secondary cell wall formation and morphogenesis. However, the relevance of microtubule-determined xylem wall thickening patterns in plant hydraulic conductivity remains unclear. In the present study, we identified a maize (Zea mays) semi-dominant mutant, designated drought-overly-sensitive1 (ZmDos1), the upper leaves of which wilted even when exposed to well-watered conditions during growth; the wilting phenotype was aggravated by increased temperatures and decreased humidity. Protoxylem vessels in the stem and leaves of the mutant showed altered thickening patterns of the secondary cell wall (from annular to spiral), decreased inner diameters, and limited water transport efficiency. The causal mutation for this phenotype was found to be a G-to-A mutation in the maize gene α-tubulin4, resulting in a single amino acid substitution at position 196 (E196K). Ectopic expression of the mutant α-tubulin4 in Arabidopsis (Arabidopsis thaliana) changed the orientation of microtubule arrays, suggesting a determinant role of this gene in microtubule assembly and secondary cell wall thickening. Our findings suggest that the spiral wall thickenings triggered by the α-tubulin mutation are stretched during organ elongation, causing a smaller inner diameter of the protoxylem vessels and affecting water transport in maize. This study underscores the importance of tubulin-mediated protoxylem wall thickening in regulating plant hydraulics, improves our understanding of the relationships between protoxylem structural features and functions, and offers candidate genes for the genetic enhancement of maize.

2.
Mol Cancer ; 23(1): 144, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004737

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents a prevalent malignant tumor, with approximately 40% of patients encountering treatment challenges or relapse attributed to rituximab resistance, primarily due to diminished or absent CD20 expression. Our prior research identified PDK4 as a key driver of rituximab resistance through its negative regulation of CD20 expression. Further investigation into PDK4's resistance mechanism and the development of advanced exosome nanoparticle complexes may unveil novel resistance targets and pave the way for innovative, effective treatment modalities for DLBCL. METHODS: We utilized a DLBCL-resistant cell line with high PDK4 expression (SU-DHL-2/R). We infected it with short hairpin RNA (shRNA) lentivirus for RNA sequencing, aiming to identify significantly downregulated mRNA in resistant cells. Techniques including immunofluorescence, immunohistochemistry, and Western blotting were employed to determine PDK4's localization and expression in resistant cells and its regulatory role in phosphorylation of Histone deacetylase 8 (HDAC8). Furthermore, we engineered advanced exosome nanoparticle complexes, aCD20@ExoCTX/siPDK4, through cellular, genetic, and chemical engineering methods. These nanoparticles underwent characterization via Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM), and their cellular uptake was assessed through flow cytometry. We evaluated the nanoparticles' effects on apoptosis in DLBCL-resistant cells and immune cells using CCK-8 assays and flow cytometry. Additionally, their capacity to counteract resistance and exert anti-tumor effects was tested in a resistant DLBCL mouse model. RESULTS: We found that PDK4 initiates HDAC8 activation by phosphorylating the Ser-39 site, suppressing CD20 protein expression through deacetylation. The aCD20@ExoCTX/siPDK4 nanoparticles served as effective intracellular delivery mechanisms for gene therapy and monoclonal antibodies, simultaneously inducing apoptosis in resistant DLBCL cells and triggering immunogenic cell death in tumor cells. This dual action effectively reversed the immunosuppressive tumor microenvironment, showcasing a synergistic therapeutic effect in a subcutaneous mouse tumor resistance model. CONCLUSIONS: This study demonstrates that PDK4 contributes to rituximab resistance in DLBCL by modulating CD20 expression via HDAC8 phosphorylation. The designed exosome nanoparticles effectively overcome this resistance by targeting the PDK4/HDAC8/CD20 pathway, representing a promising approach for drug delivery and treating patients with Rituximab-resistant DLBCL.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Exossomos , Linfoma Difuso de Grandes Células B , Nanopartículas , Rituximab , Humanos , Exossomos/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Rituximab/farmacologia , Rituximab/uso terapêutico , Animais , Camundongos , Nanopartículas/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
3.
Br J Haematol ; 204(5): 1999-2006, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38438264

RESUMO

Prolonged coagulation times, such as activated partial thromboplastin time (APTT) and thrombin time (TT), are common in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV) and have been confirmed to be related to patient's poor outcome by previous studies. To find out the reason for prolonged coagulation time in patients with SFTSV infection, and whether it predicts haemorrhagic risk or not. Seventy-eight consecutive patients with confirmed SFTSV infection were enrolled in this prospective, single-centre, observational study. Several global and specific coagulation parameters of these patients on admission were detected, and the haemorrhagic events during hospitalization and their outcomes were recorded. Most of the enrolled patients had prolonged APTT (82.1%) and TT (80.8%), normal prothrombin time (83.3%) and intrinsic coagulation factors above haemostatic levels (97.4%). The heparin-like effect was confirmed by a protamine neutralization test and anti-Xa activity detection in most patients. Interestingly, the APTT and TT results were significantly positively correlated with the levels of endothelial markers and viral load, respectively. The APTT was independently associated with the haemorrhage of patients. The prolonged APTT and TT of SFTS patients may mainly be attributed to endogenous heparinoids and are associated with increased haemorrhagic risk.


Assuntos
Hemorragia , Febre Grave com Síndrome de Trombocitopenia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Tempo de Tromboplastina Parcial , Hemorragia/sangue , Hemorragia/etiologia , Estudos Prospectivos , Febre Grave com Síndrome de Trombocitopenia/sangue , Heparina/uso terapêutico , Adulto , Tempo de Trombina , Phlebovirus , Coagulação Sanguínea , Fatores de Risco , Idoso de 80 Anos ou mais
4.
Small ; 20(13): e2306068, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37963834

RESUMO

Optoelectronic synapses are currently drawing significant attention as fundamental building blocks of neuromorphic computing to mimic brain functions. In this study, a two-terminal synaptic device based on a doped PdSe2 flake is proposed to imitate the key neural functions in an optical pathway. Due to the wavelength-dependent desorption of oxygen clusters near the intrinsic selenide vacancy defects, the doped PdSe2 photodetector achieves a high negative photoresponsivity of -7.8 × 103 A W-1 at 473 nm and a positive photoresponsivity of 181 A W-1 at 1064 nm. This wavelength-selective bi-direction photoresponse endows an all-optical pathway to imitate the fundamental functions of artificial synapses on a device level, such as psychological learning and forgetting capability, as well as dynamic logic functions. The underpinning photoresponse is further demonstrated on a flexible platform, providing a viable technology for neuromorphic computing in wearable electronics. Furthermore, the p-type doping results in an effective increase of the channel's electrical conductivity and a significant reduction in power consumption. Such low-power-consuming optical synapses with simple device architecture and low-dimensional features demonstrate tremendous promise for building multifunctional artificial neuromorphic systems in the future.

5.
J Virol ; 97(3): e0001623, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36794935

RESUMO

Viruses require host cell metabolic reprogramming to satisfy their replication demands; however, the mechanism by which the Newcastle disease virus (NDV) remodels nucleotide metabolism to support self-replication remains unknown. In this study, we demonstrate that NDV relies on the oxidative pentose phosphate pathway (oxPPP) and the folate-mediated one-carbon metabolic pathway to support replication. In concert with [1,2-13C2] glucose metabolic flow, NDV used oxPPP to promote pentose phosphate synthesis and to increase antioxidant NADPH production. Metabolic flux experiments using [2,3,3-2H] serine revealed that NDV increased one-carbon (1C) unit synthesis flux through the mitochondrial 1C pathway. Interestingly, methylenetetrahydrofolate dehydrogenase (MTHFD2) was upregulated as a compensatory mechanism for insufficient serine availability. Unexpectedly, direct knockdown of enzymes in the one-carbon metabolic pathway, except for cytosolic MTHFD1, significantly inhibited NDV replication. Specific complementation rescue experiments on small interfering RNA (siRNA)-mediated knockdown further revealed that only a knockdown of MTHFD2 strongly restrained NDV replication and was rescued by formate and extracellular nucleotides. These findings indicated that NDV replication relies on MTHFD2 to maintain nucleotide availability. Notably, nuclear MTHFD2 expression was increased during NDV infection and could represent a pathway by which NDV steals nucleotides from the nucleus. Collectively, these data reveal that NDV replication is regulated by the c-Myc-mediated 1C metabolic pathway and that the mechanism of nucleotide synthesis for viral replication is regulated by MTHFD2. IMPORTANCE Newcastle disease virus (NDV) is a dominant vector for vaccine and gene therapy that accommodates foreign genes well but can only infect mammalian cells that have undergone cancerous transformation. Understanding the remodeling of nucleotide metabolic pathways in host cells by NDV proliferation provides a new perspective for the precise use of NDV as a vector or in antiviral research. In this study, we demonstrated that NDV replication is strictly dependent on pathways involved in redox homeostasis in the nucleotide synthesis pathway, including the oxPPP and the mitochondrial one-carbon pathway. Further investigation revealed the potential involvement of NDV replication-dependent nucleotide availability in promoting MTHFD2 nuclear localization. Our findings highlight the differential dependence of NDV on enzymes for one-carbon metabolism, and the unique mechanism of action of MTHFD2 in viral replication, thereby providing a novel target for antiviral or oncolytic virus therapy.


Assuntos
Metilenotetra-Hidrofolato Desidrogenase (NADP) , Doença de Newcastle , Vírus da Doença de Newcastle , Replicação Viral , Animais , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Doença de Newcastle/enzimologia , Doença de Newcastle/fisiopatologia , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/genética , Vírus da Doença de Newcastle/metabolismo , Nucleotídeos/metabolismo , Serina/metabolismo , Replicação Viral/genética , Linhagem Celular , Células A549 , Humanos , Mesocricetus , Técnicas de Silenciamento de Genes , Transporte Proteico/genética , Mitocôndrias/enzimologia , Regulação para Cima/fisiologia
6.
Nat Mater ; 22(7): 853-859, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37349395

RESUMO

III-nitride wide bandgap semiconductors are promising materials for modern optoelectronics and electronics. Their application has progressed greatly thanks to the continuous quality improvements of heteroepitaxial films grown on large-lattice-mismatched foreign substrates. But compared with bulk single crystals, there is still tremendous room for the further improvement of the material quality. Here we show a paradigm to achieve high-quality III-nitride heteroepitaxial films by the controllable discretization and coalescence of columns. By adopting nano-patterned AlN/sapphire templates with regular hexagonal holes, discrete AlN columns coalesce with uniform out-of-plane and in-plane orientations guaranteed by sapphire nitridation pretreatment and the ordered lateral growth of cleavage facets, which efficiently suppresses the regeneration of threading dislocations during coalescence. The density of dislocation etch pits in the AlN heteroepitaxial film reaches 3.3 × 104 cm-2, close to the present available AlN bulk single crystals. This study facilitates the growth of bulk-class quality III-nitride films featuring low cost and scalability.


Assuntos
Óxido de Alumínio , Eletrônica , Semicondutores , Software
7.
Semin Thromb Hemost ; 50(4): 592-604, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38395068

RESUMO

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare, acquired coagulopathy syndrome. Here, we aim to summarize the clinical features of LAHPS to improve the understanding of the disease. The clinical data of 52 patients with LAHPS retrieved through PubMed from 2019 to 2023, supplemented with a local case of a child with LAHPS, were retrospectively analyzed, and the clinical characteristics were summarized. 56.6% of LAHPS patients were female, the median age at onset was 13.0 years (range, 1.2-85 years), and the median activity of factor II was 18.0% (range, 0.1-69%). 64.2% of LAHPS patients experienced hemorrhage, with 29.4% having multisite hemorrhage and 20.6% experiencing both nonsevere and severe hemorrhage. Most of the reported cases were secondary to autoimmune diseases (60.6%), followed by infections (33.3%). Corticosteroids were administered to 79.3% of patients with hemorrhage, and 90.6% of patients with LAHPS showed improvement. In conclusion, LAHPS is most commonly observed in female patients, particularly those under 18 years of age. LAHPS is characterized by hemorrhage, occurring at various sites and with varying degrees of severity, but the majority of patients improve with appropriate treatment and management.


Assuntos
Hipoprotrombinemias , Inibidor de Coagulação do Lúpus , Humanos , Hipoprotrombinemias/sangue , Hipoprotrombinemias/complicações , Feminino , Inibidor de Coagulação do Lúpus/sangue , Pré-Escolar , Criança , Adolescente , População do Leste Asiático
8.
New Phytol ; 241(3): 1115-1129, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37723553

RESUMO

The peptidoglycan (PG) layer, a core component of the bacterial cell wall, has been retained in the Physcomitrium patens chloroplasts. The PG layer entirely encompasses the P. patens chloroplast, including the division site, but how PG biosynthesis cooperates with the constriction of two envelope membranes at the chloroplast division site remains elusive. Here, focusing on the PG synthase penicillin-binding protein (PBP), we performed cytological and molecular analyses to dissect the mechanism of chloroplast division in P. patens. We showed that PBP, acting in the final step of PG biosynthesis, is likely a chloroplast inner envelope protein that can aggregate at mid-chloroplasts during chloroplast division. Physcomitrium patens had five orthologs of PLASTID DIVISION2 (PDV2), an outer envelope component of the chloroplast division complex. Our data indicated that PpPDV2 proteins interact with PpPBP and are responsible for recruiting PpPBP to the chloroplast division site, in addition to PpDRP5B. Furthermore, we found that PBP deletion and carbenicillin application restrain constriction of the chloroplast division complex, rather than its assembly. This work provides direct molecular evidence for a link between chloroplast division of P. patens and PG biosynthesis and indicates that PG biosynthesis is required for the constriction of the chloroplast division apparatus in P. patens.


Assuntos
Peptidoglicano , Plastídeos , Peptidoglicano/metabolismo , Plastídeos/metabolismo , Cloroplastos/metabolismo , Parede Celular/metabolismo
9.
New Phytol ; 242(1): 154-169, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38375601

RESUMO

Phloem sieve elements (PSE), the primary conduits collaborating with neighboring phloem pole pericycle (PPP) cells to facilitate unloading in Arabidopsis roots, undergo a series of developmental stages before achieving maturation and functionality. However, the mechanism that maintains the proper progression of these differentiation stages remains largely unknown. We identified a gain-of-function mutant altered phloem pole pericycle 1 Dominant (app1D), producing a truncated, nuclear-localized active form of NAC with Transmembrane Motif 1-like (NTL9). This mutation leads to ectopic expression of its downstream target CALLOSE SYNTHASE 8 (CalS8), thereby inducing callose accumulation, impeding SE differentiation, impairing phloem transport, and inhibiting root growth. The app1D phenotype could be reproduced by blocking the symplastic channels of cells within APP1 expression domain in wild-type (WT) roots. The WT APP1 is primarily membrane-tethered and dormant in the root meristem cells but entries into the nucleus in several cells in PPP near the unloading region, and this import is inhibited by blocking the symplastic intercellular transport in differentiating SE. Our results suggest a potential maintenance mechanism involving an APP1-CalS8 module, which induces CalS8 expression and modulates symplastic communication, and the proper activation of this module is crucial for the successful differentiation of SE in the Arabidopsis root.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Glucanos , Glucosiltransferases , Arabidopsis/metabolismo , Floema/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
10.
Respir Res ; 25(1): 253, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38902698

RESUMO

BACKGROUND: There is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC. METHODS: The data of our study was obtained from IMpower133 study. A total of 202 patients with SCLC received the treatment of placebo plus carboplatin plus etoposide (EC) while a total of 201 patients with SCLC received the treatment of atezolizumab plus EC. Overall survival (OS) was compared using Kaplan Meier analyses. Univariate and multivariate Cox regression analysis were used to determine independent prognostic variables affecting OS in patients with SCLC. RESULTS: We have demonstrated that a higher TMB adjusted by a lower neutrophil-to-lymphocyte ratio (NLR) is significantly correlated with improved OS, in patients with SCLC subject to either atezolizumab or placebo (P = 0.001 for atezolizumab and P = 0.034 for placebo). Moreover, Cox model showed that TMB < 10 mut/Mb adjusted by NLR ≥ median was an independent factor of OS for atezolizumab-treated SCLC patients (hazard ratio [HR], 2.82; 95% confidence interval; 1.52-5.24; P = 0.001). Both univariate and multivariate cox regression analysis showed that for patients with SCLC harboring low NLR and high TMB, survival is significantly longer in those treated with atezolizumab than those treated with placebo. Survival benefit is significantly higher in atezolizumab-treated patients with SCLC than those treated with placebo (P = 0.018 for TMB cutoff = 10 mut/Mb, P = 0.034 for TMB cutoff = 16 mut/Mb). CONCLUSION: Our findings provide a promising insight into the utility of NLR-adjusted TMB in the prognosis and immune responses in patients with SCLC.


Assuntos
Anticorpos Monoclonais Humanizados , Biomarcadores Tumorais , Neoplasias Pulmonares , Linfócitos , Neutrófilos , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Feminino , Linfócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Mutação , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Linfócitos , Método Duplo-Cego
11.
BMC Cancer ; 24(1): 361, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509471

RESUMO

BACKGROUND: Breast cancer is the most common female malignancy worldwide and a major cause of morbidity and mortality. Exercise during adjuvant treatment improves function and relieves symptoms in breast cancer survivors. However, it is unclear if an unsupervised exercise programme may be as effective as a supervised multimodal group. We investigated the feasibility and efficacy of a centre-based multidimensional rehabilitation (MDR) programme for breast cancer survivors undergoing adjuvant treatment and compared it to an unsupervised home-based exercise (HE) programme. METHODS: Participants were self-allocated to either MDR or HE group. MDR participants underwent 24 supervised exercise classes and 10 education classes over 12 weeks. HE participants were instructed on a home exercise regime. Outcome measures, including the 6-min walk test (6MWT) and Frenchay Activities Index (FAI), FACT-Cognitive Function scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, were conducted at baseline (W0), post-intervention (W12) and 6-months post-intervention (M6). Variance between time points and the 2 groups were analysed using a linear mixed model (unstructured covariance matrix) and adjusted with Bonferroni. RESULT: Twenty-five participants attended at least half of the MDR interventions, while 21 completed the HE interventions. The former showed significant improvement in 6MWT, from 406.88 m (W0) to 443.34 m (W12) to 452.81 m (M6), while the improvement in the HE group was not significant (407.67 m (W0) to 433.14 m (W12) to 430.96 m (M6)). Both groups showed a significant improvement in FAI, with earlier significant improvement noted at W12 in the MDR group (22.71 (W0) to 27.65 (W12) to 28.81 (M6)) compared to the HE group (23.16 (W0) to 26.47 (W12) to 29.85 (M6)). Dropout rate was 16% in the MDR group and 34% in HE group. Overall satisfaction with the MDR programme was high. CONCLUSION: Both MDR and HE programmes were feasible. MDR was superior in improving endurance and earlier return to instrumental activities for those who completed at least half of the sessions. Future studies could explore use of technology to improve adherence to exercise. TRIAL REGISTRATION: The study was registered with ClinicalTrial.gov on 01/04/2022 with the registration number NCT05306808.


Assuntos
Neoplasias da Mama , Qualidade de Vida , Sulfonamidas , Humanos , Feminino , Neoplasias da Mama/terapia , Terapia por Exercício , Exercício Físico
12.
Environ Sci Technol ; 58(18): 8053-8064, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38662987

RESUMO

The aggregation behavior of ubiquitous dissolved black carbon (DBC) largely affects the fate and transport of its own contaminants and the attached contaminants. However, the photoaging processes and resulting effects on its colloidal stability remain yet unknown. Herein, dissolved biochars (DBioCs) were extracted from common wheat straw biochar as a proxy for an anthropogenic DBC. The influences of UV radiation on their aggregation kinetics were systematically investigated under various water chemistries (pH, electrolytes, and protein). The environmental stability of the DBioCs before and after radiation was further verified in two natural water samples. Hamaker constants of pristine and photoaged DBioCs were derived according to Derjaguin-Landau-Verwey-Overbeek (DLVO) prediction, and its attenuation (3.19 ± 0.15 × 10-21 J to 1.55 ± 0.07 × 10-21 J after 7 days of radiation) was described with decay kinetic models. Pearson correlation analysis revealed that the surface properties and aggregation behaviors of DBioCs were significantly correlated with radiation time (p < 0.05), indicating its profound effects. Based on characterization and experimental results, we proposed a three-stage mechanism (contended by photodecarboxylation, photo-oxidation, and mineral exposure) that DBioCs might experience under UV radiation. These findings would provide an important reference for potential phototransformation processes and relevant behavioral changes that DBC may encounter.


Assuntos
Raios Ultravioleta , Água/química , Carvão Vegetal/química , Cinética , Poluentes Químicos da Água/química
13.
Environ Res ; 257: 119267, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38815718

RESUMO

Natural pyrethrins are widely used in agriculture because of their good insecticidal activity. Meanwhile, natural pyrethrins play an important role in the safety evaluation of pyrethroids as precursors for structural development of pyrethroid insecticides. However, there are fewer studies evaluating the neurological safety of natural pyrethrins on non-target organisms. In this study, we used SH-SY5Y cells and zebrafish embryos to explore the neurotoxicity of natural pyrethrins. Natural pyrethrins were able to induce SH-SY5Y cells damage, as evidenced by decreased viability, cycle block, apoptosis and DNA damage. The apoptotic pathway may be related to the involvement of mitochondria and the results showed that natural pyrethrins induced a rise in Capase-3 viability, Ca2+ overload, a decrease in adenosine triphosphate (ATP) and a collapse of mitochondrial membrane potential in SH-SY5Y cells. Natural pyrethrins may mediate DNA damage in SH-SY5Y cells through oxidative stress. The results showed that natural pyrethrins induced an increase in reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and catalase (CAT) activity, and induced a decrease in glutathione peroxidase (GPx) activity in SH-SY5Y cells. In vivo, natural pyrethrins induced developmental malformations in zebrafish embryos, which were mainly characterized by pericardial edema and yolk sac edema. Meanwhile, the results showed that natural pyrethrins induced damage to the Huc-GFP axis and disturbed lipid metabolism in the head of zebrafish embryos. Further results showed elevated ROS levels and apoptosis in the head of zebrafish embryos, which corroborated with the results of the cell model. Finally, the results of mRNA expression assay of neurodevelopment-related genes indicated that natural pyrethrins exposure interfered with their expression and led to neurodevelopmental damage in zebrafish embryos. Our study may raise concerns about the neurological safety of natural pyrethrins on non-target organisms.


Assuntos
Embrião não Mamífero , Piretrinas , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Piretrinas/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Inseticidas/toxicidade , Dano ao DNA/efeitos dos fármacos , Linhagem Celular Tumoral , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
14.
Plant Cell Rep ; 43(3): 79, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400858

RESUMO

KEY MESSAGE: High-frequency clonal seeds and near-normal fertility were obtained by engineering synthetic apomixis in hybrid rice. The one-line strategy, with the advantage of unnecessary seed production, is the final stage for the hybrid rice development and can be achieved through the fixation of heterosis via artificially inducing apomixis. Recently, synthetic apomixis has been generated in rice by combining MiMe (Mitosis instead of Meiosis) with either the ectopic expression of BABY BOOM (BBM1 or BBM4) or mutation of MATRILINEAL (MTL), resulting in over 95.00% of clonal seeds. However, the frequency of clonal seeds was only 29.20% when AtDD45 promoter was used to drive BBM1. In addition, achieving both a high frequency of clonal seeds and near-normal fertility simultaneously had been elusive in earlier strategies. In this study, using AtDD45 promoter to drive BBM1 expression in combination with the MiMe mutant resulted in the apomixis frequency as high as 98.70%. Even more, employing fusion promoters (AtMYB98_AtDD1_OsECA1-like1) to drive WUS expression in combination with pAtDD45:BBM1 and MiMe could produce clonal seeds at rates of up to 98.21%, the highest seed setting rate reached to 83.67%. Multiple-embryos were observed in clonal lines at a frequency ranging from 3.37% to 60.99%. Transmission of the high frequency of apomixis through skipped generations (atavism) was identified in two clonal lines, even though it remained stable in the majority of clonal lines. These findings significantly advance the pursuit of fixed heterosis in rice through synthetic apomixis, edging closer to its agricultural application.


Assuntos
Apomixia , Oryza , Oryza/genética , Apomixia/genética , Sementes/genética , Vigor Híbrido/genética , Fertilidade/genética
15.
Plant Dis ; : PDIS09231880RE, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37858967

RESUMO

The fungus Coleosporium zanthoxyli causes leaf rust in Chinese pepper (Zanthoxylum armatum). To investigate the control effect of elicitor treatment on leaf rust in this species, the impact of salicylic acid (SA) on the spores and growth of C. zanthoxyli and the induced resistance to leaf rust by Z. armatum were analyzed, and the possible defense mechanisms involved in SA induction were evaluated. The results showed that SA had no effect on C. zanthoxyli spore germination and growth; however, rust resistance was induced in Z. armatum. The optimal SA treatment concentration was 0.4 mg/ml, and the relative cure effect reached 44.56%. SA-induced disease resistance was evident for up to 10 days, while the optimal induction interval was 48 h after stimulation. Consistent with the induced resistance, H2O2, total protein, total phenol, and lignin concentrations and polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia lyase (PAL), superoxide dismutase (SOD), and catalase (CAT) activities were significantly increased with the SA treatment, whereas the malondialdehyde content was significantly decreased. In addition, exogenous SA promoted defense-related enzyme activities, including those of POD, CAT, and PAL, and increased H2O2, lignin, and endogenous SA contents. Furthermore, SA induced the expression of SA signaling pathway genes such as ZaPR1 and ZaNPR1, and silencing ZaPR1 enhanced the sensitivity of Z. armatum to leaf rust. Our results demonstrated that 0.4 mg/ml SA priming increased the activities of CAT, POD, and PAL, elevated the contents of H2O2, lignin, and endogenous SA, and upregulated the expression of the SA-related gene ZaPR1, thereby enhancing the resistance of Z. armatum to leaf rust.

16.
Sensors (Basel) ; 24(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38474978

RESUMO

The synergistic effects on the 0.18 µm PPD CISs induced by neutron displacement damage and gamma ionization damage are investigated. The typical characterizations of the CISs induced by the neutron displacement damage and gamma ionization damage are presented separately. The CISs are irradiated by reactor neutron beams up to 1 × 1011 n/cm2 (1 MeV neutron equivalent fluence) and 60Co γ-rays up to the total ionizing dose level of 200 krad(Si) with different sequential order. The experimental results show that the mean dark signal increase in the CISs induced by reactor neutron radiation has not been influenced by previous 60Co γ-ray radiation. However, the mean dark signal increase in the CISs induced by 60Co γ-ray radiation has been remarkably influenced by previous reactor neutron radiation. The synergistic effects on the PPD CISs are discussed by combining the experimental results and the TCAD simulation results of radiation damage.

17.
Nano Lett ; 23(20): 9522-9528, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37823381

RESUMO

Constructing high-quality homojunctions plays a pivotal role for the advancement of two-dimensional transition metal sulfide (TMDC) based optoelectronic devices. Here, a lateral PdSe2 p-i-n homojunction is constructed by electrostatic doping. Electrical measurements reveal that the homojunction diode exhibits a strong rectifying characteristic with a rectification ratio exceeding 104 and an ideality factor approaching 1. When functioning in photovoltaic mode, the device achieves a high responsivity of 1.1 A/W under 1064 nm illumination, with a specific detectivity of 1.3 × 1011 Jones and a high linearity of 45 dB. Benefiting from the lateral p-i-n structure, the junction capacitance is significantly reduced, and an ultrafast response (3/6 µs) is obtained. Additionally, the photodiode has the capability of polarization distinction due to the unique in-plane anisotropic structure of PdSe2, exhibiting a dichroic ratio of 1.6 at a 1064 nm wavelength. This high-performance polarization-sensitive near-infrared photodetector exhibits great potential in the next-generation optoelectronic applications.

18.
Nano Lett ; 23(24): 11485-11492, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38063397

RESUMO

The spin Hall effect (SHE) can generate a pure spin current by an electric current, which is promisingly used to electrically control magnetization. To reduce the power consumption of this control, a giant spin Hall angle (SHA) in the SHE is desired in low-resistivity systems for practical applications. Here, critical spin fluctuation near the antiferromagnetic (AFM) phase transition in chromium (Cr) is proven to be an effective mechanism for creating an additional part of the SHE, named the fluctuation spin Hall effect. The SHA is significantly enhanced when the temperature approaches the Néel temperature (TN) of Cr and has a peak value of -0.36 near TN. This value is higher than the room-temperature value by 153% and leads to a low normalized power consumption among known spin-orbit torque materials. This study demonstrates the critical spin fluctuation as a prospective way to increase the SHA and enriches the AFM material candidates for spin-orbitronic devices.

19.
Funct Integr Genomics ; 23(4): 334, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37962640

RESUMO

Glioma is the most common malignancy in the central nervous system. This study aims to disclose the impacts of Xihuang pill (XHP), a traditional Chinese formula, on glioma cell pyroptosis and relevant molecular mechanism. U251 and SHG-44 cells were treated with XHP alone or together with oe-POU4F1 and sh-STAT3. CCK8 assay detected the viability, flow cytometry evaluated pyroptosis, and microscopy observed cell morphology. LDH release was determined by the LDH kit and the levels of IL-1ß and IL-18 were detected by ELISA. Immunofluorescence showed NLRP3 expression in glioma cells and western blotting measured the levels of POU4F1, STAT3, NLRP3, ASC, cleaved caspase-1, and IL-1ß. The binding of POU4F1 to STAT3 was verified. Primary glioma model was established to observe tumor change by in vivo imaging, determine the levels of Ki67 and NLRP3 by immunochemistry, and detect relevant protein levels by western blotting. XHP treatment alone downregulated POU4F1 and STAT3 levels, aroused pyroptotic appearance in glioma cells such as ballooning swelling, reduced cell viability and number of pyroptotic cells, increased LDH release and IL-1ß and IL-18 levels, formed NLRP3 sports in cells, and elevated the levels of pyroptosis-related proteins. However, POU4F1 overexpression or STAT3 silencing suppressed XHP-promoted pyroptosis. Mechanistically, POU4F1 acted as a transcription factor of STAT3 and regulated its transcription. In primary glioma models, XHP enhanced glioma cell pyroptosis and blocked glioma growth. XHP facilitates glioma cell pyroptosis via the POU4F1/STAT3 axis.


Assuntos
Glioma , Interleucina-18 , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Glioma/tratamento farmacológico , Glioma/genética , Fator de Transcrição Brn-3A , Fator de Transcrição STAT3/genética
20.
Biomacromolecules ; 24(8): 3557-3567, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37458565

RESUMO

The application of flexible wearable sensing devices based on conductive hydrogels in human motion signal monitoring has been widely studied. However, conventional conductive hydrogels contain a large amount of water, resulting in poor mechanical properties and limiting their application in harsh environments. Here, a simple one-pot method for preparing conductive hydrogels is proposed, that is, polyvinyl alcohol (PVA), wheat protein (WP), and lithium chloride (LiCl) are dissolved in an ethylene glycol (EG)/water binary solvent. The obtained PVA/EG/WP (PEW) conductive organohydrogel has good mechanical properties, and its tensile strength and elongation at break reach 1.19 MPa and 531%, respectively, which can withstand a load of more than 6000 times its own weight without breaking. The binary solvent system composed of EG/water endows the hydrogel with good frost resistance and water retention. PEW organohydrogel as a wearable strain sensor also has good strain sensitivity (GF = 2.36), which can be used to detect the movement and physiological activity signals in different parts of the human body. In addition, PEW organohydrogels exhibit good degradability, reducing the environmental footprint of the flexible sensors after disposal. This research provides a new and viable way to prepare a new generation of environmentally friendly sensors.


Assuntos
Álcool de Polivinil , Triticum , Humanos , Glicóis , Solventes , Condutividade Elétrica , Hidrogéis
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