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1.
Proc Natl Acad Sci U S A ; 121(7): e2318970121, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38315838

RESUMEN

Solar-driven photocatalytic CO2 reduction is an energy-efficient and sustainable strategy to mitigate CO2 levels in the atmosphere. However, efficient and selective conversion of CO2 into multi-carbon products, like C2H4, remains a great challenge due to slow multi-electron-proton transfer and sluggish C-C coupling. Herein, a two-dimensional thin-layered hybrid perovskite is fabricated through filling of oxygen into iodine vacancy in pristine DMASnI3 (DMA = dimethylammonium). The rational-designed DMASnI3(O) induces shrinkage of active sites distance and facilitates dimerization of C-C coupling of intermediates. Upon simulated solar irradiation, the DMASnI3(O) photocatalyst achieves a high selectivity of 74.5%, corresponding to an impressive electron selectivity of 94.6%, for CO2 to C2H4 conversion and an effective C2H4 yield of 11.2 µmol g-1 h-1. In addition, the DMASnI3(O) inherits excellent water stability and implements long-term photocatalytic CO2 reduction to C2H4 in a water medium. This work establishes a unique paradigm to convert CO2 to C2+ hydrocarbons in a perovskite-based photocatalytic system.

2.
Development ; 150(9)2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37073949

RESUMEN

De novo root regeneration (DNRR) is a developmental process that regenerates adventitious roots from wounded tissues. Phytohormone signaling pathways involved in microbial resistance are mobilized after cutting and influence de novo root regeneration. Microbes may positively or negatively influence the development and stress responses of a plant. However, most studies on the molecular mechanisms of de novo organogenesis are performed in aseptic conditions. Thus, the potential crosstalk between organ regeneration and biotic stresses is underexplored. Here, we report the development of a versatile experimental system to study the impact of microbes on DNRR. Using this system, we found that bacteria inhibited root regeneration by activation of, but not limited to, pathogen-associated molecular pattern (PAMP)-triggered immunity. Sensing bacteria-derived flagellin 22 peptide (flg22) inhibited root regeneration by interfering with the formation of an auxin maximum at the wound site. This inhibition relies on the receptor complex that recognizes microbial patterns but may bypass the requirement of salicylic acid signaling.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
3.
PLoS Genet ; 19(3): e1010636, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36857386

RESUMEN

Plants can regenerate new organs from damaged or detached tissues. In the process of de novo root regeneration (DNRR), adventitious roots are frequently formed from the wound site on a detached leaf. Salicylic acid (SA) is a key phytohormone regulating plant defenses and stress responses. The role of SA and its acting mechanisms during de novo organogenesis is still unclear. Here, we found that endogenous SA inhibited the adventitious root formation after cutting. Free SA rapidly accumulated at the wound site, which was accompanied by an activation of SA response. SA receptors NPR3 and NPR4, but not NPR1, were required for DNRR. Wounding-elevated SA compromised the expression of AUX1, and subsequent transport of auxin to the wound site. A mutation in AUX1 abolished the enhanced DNRR in low SA mutants. Our work elucidates a role of SA in regulating DNRR and suggests a potential link between biotic stress and tissue regeneration.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácido Salicílico/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo , Hojas de la Planta/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
4.
Biochem Biophys Res Commun ; 719: 150096, 2024 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-38749091

RESUMEN

Protein S-nitrosylation, which is defined by the covalent attachment of nitric oxide (NO) to the thiol group of cysteine residues, is known to play critical roles in plant development and stress responses. NO promotes seedling photomorphogenesis and NO emission is enhanced by light. However, the function of protein S-nitrosylation in plant photomorphogenesis is largely unknown. E3 ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and transcription factor ELONGATED HYPOCOTYL 5 (HY5) antagonistically regulate seedling photomorphogenesis. COP1 inhibits plant photomorphogenesis by targeting photomorphogenic promoters like HY5 for 26S proteasome degradation. Here, we report that COP1 is S-nitrosylated in vitro. Mass spectrometry analyses revealed that two evolutionarily well conserved residues, cysteine 425 and cysteine 607, in the WD40 domain of COP1 are S-nitrosylated. S-nitrosylated glutathione (GSNO) is an important physiological NO donor for protein S-nitrosylation. The Arabidopsis (Arabidopsis thaliana) gsnor1-3 mutant, which accumulates higher level of GSNO, accumulated higher HY5 levels than wildtype (WT), indicating that COP1 activity is inhibited. Protein S-nitrosylation can be reversed by Thioredoxin-h5 (TRXh5) in plants. Indeed, COP1 interacts directly with TRXh5 and its close homolog TRXh3. Moreover, catalase 3 (CAT3) acts as a transnitrosylase that transfers NO to its target proteins like GSNO reductase (GSNOR). We found that CAT3 interacts with COP1 in plants. Taken together, our data indicate that the activity of COP1 is likely inhibited by NO via S-nitrosylation to promote the accumulation of HY5 and photomorphogenesis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Óxido Nítrico , Ubiquitina-Proteína Ligasas , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Óxido Nítrico/metabolismo , Luz , Cisteína/metabolismo , Plantones/metabolismo , Plantones/crecimiento & desarrollo , Plantones/genética , Aldehído Oxidorreductasas/metabolismo , Aldehído Oxidorreductasas/genética , Regulación de la Expresión Génica de las Plantas
5.
Small ; 20(29): e2311661, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38597694

RESUMEN

Electronically conductive protein-based materials can enable the creation of bioelectronic components and devices from sustainable and nontoxic materials, while also being well-suited to interface with biological systems, such as living cells, for biosensor applications. However, as proteins are generally electrical insulators, the ability to render protein assemblies electroactive in a tailorable manner can usher in a plethora of useful materials. Here, an approach to fabricate electronically conductive protein nanowires is presented by aligning heme molecules in proximity along protein filaments, with these nanowires also possessing charge transfer abilities that enable energy harvesting from ambient humidity. The heme-incorporated protein nanowires demonstrate electron transfer over micrometer distances, with conductive atomic force microscopy showing individual nanowires having comparable conductance to other previously characterized heme-based bacterial nanowires. Exposure of multilayer nanowire films to humidity produces an electrical current, presumably through water molecules ionizing carboxyl groups in the filament and creating an unbalanced total charge distribution that is enhanced by the heme. Incorporation of heme and potentially other metal-center porphyrin molecules into protein nanostructures could pave the way for structurally- and electrically-defined protein-based bioelectronic devices.


Asunto(s)
Conductividad Eléctrica , Hemo , Nanocables , Nanocables/química , Hemo/química , Microscopía de Fuerza Atómica , Proteínas/química
6.
J Exp Bot ; 75(5): 1213-1216, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38416207

RESUMEN

This article comments on: Wu Y, Sexton WK, Zhang Q, Bloodgood D, Wu Y, Hooks C, Coker F, Vasquez A, Wei C-I, Xiao S. 2024. Leaf abaxial immunity to powdery mildew in Arabidopsis is conferred by multiple defense mechanisms. Journal of Experimental Botany 75, 1465-1478.


Asunto(s)
Arabidopsis , Botánica , Arabidopsis/genética , Hojas de la Planta
7.
Cancer Cell Int ; 24(1): 127, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580966

RESUMEN

BACKGROUND: Cancer-associated fibroblasts (CAFs) drive cancer progression and treatment failure on one hand, while their tumor-restraining functions are also observed on the other. Recent single cell RNA sequencing (scRNA-seq) analyses demonstrates heterogeneity of CAFs and defines molecular subtypes of CAFs, which help explain their different functions. However, it remains unclear whether these CAF subtypes have the same or different biological/clinical implications in prostate cancer (PCa) or other malignancies. METHODS: PCa cells were incubated with supernatant from normal fibroblasts and CAFs to assess their effects on cell behaviors. Sequencing, genomic, and clinical data were collected from TCGA, MSKCC, CPGEA and GEO databases. CAF molecular subtypes and total CAF scores were constructed and grouped into low and high groups based on CAF-specific gene expression. Progression free interval (PFI), clinicopathological features, telomere length, immune cell infiltration, drug treatment and somatic mutations were compared among CAF molecular subtypes and low/high score groups. RESULTS: The PCa CAF-derived supernatant promoted PCa cell proliferation and invasion. Based on differentially expressed genes identified by scRNA-seq analyses, we classified CAFs into 6 molecular subtypes in PCa tumors, and each subtype was then categorized into score-high and low groups according to the subtype-specific gene expression level. Such score models in 6 CAF subtypes all predicted PFI. Telomeres were significantly shorter in high-score tumors. The total CAF score from 6 CAF subtypes was also associated with PFI in PCa patients inversely, which was consistent with results from cellular experiments. Immunosuppressive microenvironment occurred more frequently in tumors with a high CAF score, which was characterized by increased CTLA4 expression and indicated better responses to CTLA4 inhibitors. Moreover, this model can also serve as a useful PFI predictor in pan-cancers. CONCLUSION: By combining scRNA-seq and bulk RNA-seq data analyses, we develop a CAF subtype score system as a prognostic factor for PCa and other cancer types. This model system also helps distinguish different immune-suppressive mechanisms in PCa, suggesting its implications in predicting response to immunotherapy. Thus, the present findings should contribute to personalized PCa intervention.

8.
Prostaglandins Other Lipid Mediat ; 174: 106871, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38992854

RESUMEN

This mini-review addresses lipoxygenases and receptors for leukotrienes in hematological malignancies. Potential novel biomarkers and drug targets in leukemia and B-cell lymphoma are discussed.


Asunto(s)
Leucemia , Linfoma , Receptores de Leucotrienos , Humanos , Receptores de Leucotrienos/metabolismo , Receptores de Leucotrienos/genética , Leucemia/metabolismo , Leucemia/genética , Leucemia/patología , Linfoma/metabolismo , Linfoma/genética , Linfoma/patología , Lipooxigenasas/metabolismo , Animales
9.
Environ Sci Technol ; 58(6): 2774-2785, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38299516

RESUMEN

Wetlands have long been recognized as efficient nitrogen (N) processing systems. While widespread interest is in constructing wetlands to mitigate N pollution, there is a dearth of information about the environmental consequences following wetland dismantlement. This study elucidated the changing trajectories of water quality and N removal capacity in a headwater river that initially contained a series of constructed wetlands but later underwent wetland destruction. An estimated 17% surge in total N concentration has been reported since the wetlands' destruction. This adverse trend is primarily attributed to a weakened in-stream N removal capacity, which was reduced to a mere 25% of the levels observed when the wetlands were operational. Further analysis confirms that the presence of wetlands actively shapes desirable environmental settings for N processing. In stark contrast, wetland destruction leads to unfavorable environmental conditions, which not only restrain in-stream anaerobic metabolisms but also trigger algal proliferation and biological N fixation. Collectively, this research provides compelling evidence of the detrimental consequences associated with wetland destruction, emphasizing the need for remedial strategies to mitigate these negative effects.


Asunto(s)
Desnitrificación , Humedales , Ríos , Nitrógeno/análisis , Nitrógeno/metabolismo , Calidad del Agua
10.
Molecules ; 29(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38611806

RESUMEN

The recent global pandemic of coronavirus disease 2019 (COVID-19) has enormously promoted the development of diagnostic technology. To control the spread of pandemic diseases and achieve rapid screening of the population, ensuring that patients receive timely treatment, rapid diagnosis has become the top priority in the development of clinical technology. This review article aims to summarize the current rapid nucleic acid diagnostic technologies applied to pandemic disease diagnosis, from rapid extraction and rapid amplification to rapid detection. We also discuss future prospects in the development of rapid nucleic acid diagnostic technologies.


Asunto(s)
COVID-19 , Ácidos Nucleicos , Humanos , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiología , Tecnología , Prueba de COVID-19
11.
Osteoarthritis Cartilage ; 31(12): 1644-1649, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37598744

RESUMEN

OBJECTIVES: To explore factors that were associated with meniscus volume in knees free of radiographic osteoarthritis (OA) features and symptoms of OA. METHODS: In the third Rotterdam Study cohort, clinical, radiographic, and magnetic resonance data were obtained at baseline (BL) and after 5 years of follow-up. Meniscus volumes and their change over time were calculated after semi-automatic segmentation on Magnetic Resonance Imaging. Knees with radiographic OA features (Kellgren and Lawrence>0) or clinical diagnosis of OA (American College of Rheumatology) at BL were excluded. Ten OA risk factors were adjusted in the multivariable analysis (generalized estimating equations), treating two knees within subjects as repeated measurements. RESULTS: From 1065 knees (570 subjects), the average (standard deviation) age and Body mass index (BMI) of included subjects were 54.3 (3.7) years and 26.5 (4.4) kg/m2. At BL, nine factors (varus alignment, higher BMI, meniscus pathologies, meniscus extrusion, cartilage lesions, injury, greater physical activity level, quadriceps muscle strength, and higher age) were significantly associated with greater meniscus volume. Five factors (injury, meniscus pathologies, meniscus extrusion, higher age, and change of BMI) were significantly associated with meniscus volume loss. CONCLUSIONS: Modifiable factors (varus alignment, BMI, physical activity level, and quadriceps muscle strength) and non-modifiable factors (higher age, injury, meniscus pathologies, meniscus extrusion, and cartilage lesions) were all associated with meniscus volume or meniscus volume loss over time.


Asunto(s)
Menisco , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/patología , Radiografía , Rodilla/patología , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Imagen por Resonancia Magnética/métodos , Meniscos Tibiales/diagnóstico por imagen , Meniscos Tibiales/patología , Menisco/patología
12.
Plant Cell Environ ; 46(4): 1278-1294, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35698268

RESUMEN

Glycerolipids are essential for rice development and grain quality but its genetic regulation remains unknown. Here we report its genetic base using metabolite-based genome-wide association study and metabolite-based quantitative traits locus (QTL) analyses based on lipidomic profiles of seeds from 587 Asian cultivated rice accessions and 103 chromosomal segment substitution lines, respectively. We found that two genes encoding phosphatidylcholine (PC):diacylglycerol cholinephosphotransferase (OsLP1) and granule-bound starch synthase I (Waxy) contribute to variations in saturated triacylglycerol (TAG) and lyso-PC contents, respectively. We demonstrated that allelic variation in OsLP1 sequence between indica and japonica results in different enzymatic preference for substrate PC-16:0/16:0 and different saturated TAG levels. Further evidence demonstrated that OsLP1 also affects heading date, and that co-selection of OsLP1 and a flooding-tolerant QTL in Aus results in the abundance of saturated TAGs associated with flooding tolerance. Moreover, we revealed that the sequence polymorphisms in Waxy has pleiotropic effects on lyso-PC and amylose content. We proposed that rice seed glycerolipids have been unintentionally shaped during natural and artificial selection for adaptive or import seed quality traits. Collectively, our findings provide valuable genetic resources for rice improvement and evolutionary insights into seed glycerolipid variations in rice.


Asunto(s)
Oryza , Oryza/genética , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo/genética , Fenotipo , Semillas/genética
13.
Environ Res ; 239(Pt 1): 117199, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37806479

RESUMEN

BACKGROUND: Old industrial areas have low quality and spatial differentiation of urban green space (UGS), which makes it difficult to meet the public's physical activity needs and leads to increased health risks. The purpose of this study is to explore the equity of UGS patterns in old industrial areas and its internal relationship with residents' health status. METHODS: This study selecteds relevant indicators to evaluate the equity of UGS patterns in the Harbin area and used linear regression analysis to explore the correlation between attributes of old industrial areas and UGS patterns. Additionally, this study explored the spatial correlation of UGSs using Moran's index and hotspot analysis. Finally, a report on residents' health was generated through a questionnaire survey, using linear regression analysis to explore the factors affecting residents' self-rated health and the significance of their correlation. RESULTS: The results showed that there is an excess supply around the core industrial zone in the west, while the rural areas in the south face a serious shortage of supply. The significance between the factors representing age and income in industrial attributes and UGS pattern was less than 0.05. We observed that residents' self-rated health was positively affected by the intensity of physical activity (low intensity B = 2.073, medium intensity B = 2.359, high intensity B = 2.512) and the frequency of physical activity (B = 1.174). Ages (B = -0.597) and three generations living together (B = -3.191), which represent the industrial attributes, had a negative impact on residents' self-rated health. CONCLUSION: To a certain extent, industrial attributes aggravate the mismatch of UGS patterns, leading to abnormal areas in spatial clustering. The quality of UGS in the old industrial zone is low and the movement is not strong; thus, the population characteristics and income have become the important factors affecting the health of residents.


Asunto(s)
Ejercicio Físico , Parques Recreativos , Estado de Salud , Renta , China
14.
Cell Mol Life Sci ; 79(2): 110, 2022 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-35098380

RESUMEN

The role of telomerase reverse transcriptase (TERT) induction and telomere maintenance in carcinogenesis including cervical cancer (CC) pathogenesis has been well established. However, it remains unclear whether they affect infection of high-risk human papillomavirus (hrHPV), an initiating event for CC development. Similarly, genetic variants at the TERT locus are shown to be associated with susceptibility to CC, but it is unclear whether these SNPs modify the risk for cervical HPV infection. Here we show that in CC-derived HeLa cells, TERT overexpression inhibits, while its depletion upregulates expression of Syndecan-1 (SDC-1), a key component for HPV entry receptors. The TCGA cohort of CC analyses reveals an inverse correlation between TERT and SDC-1 expression (R = -0.23, P = 0.001). We further recruited 1330 females (520 non-HPV and 810 hrHPV-infected) without CC or high-grade cervical intraepithelial neoplasia to analyze telomeres in cervical epithelial cells and SNPs at rs2736098, rs2736100 and rs2736108, previously identified TERT SNPs for CC risk. Non-infected females exhibited age-related telomere shortening in cervical epithelial cells and their telomeres were significantly longer than those in hrHPV-infected group (1.31 ± 0.62 vs 1.19 ± 0.48, P < 0.001). There were no differences in rs2736098 and rs2736100 genotypes, but non-infected individuals had significantly a higher C-allele frequency (associated with higher TERT expression) while lower T-allele levels at rs2736108 compared with those in the hrHPV group (P = 0.020). Collectively, appropriate telomere maintenance and TERT expression in normal cervical cells may prevent CC by modulating hrHPV infection predisposition, although they are required for CC development and progression.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Infecciones por Papillomavirus/genética , Telomerasa/genética , Telómero/genética , Neoplasias del Cuello Uterino/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Epitelio/metabolismo , Epitelio/virología , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células HeLa , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Polimorfismo de Nucleótido Simple , Telomerasa/metabolismo , Telómero/enzimología , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/metabolismo , Adulto Joven
15.
Sensors (Basel) ; 23(4)2023 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-36850908

RESUMEN

The zero-shot image classification (ZSIC) is designed to solve the classification problem when the sample is very small, or the category is missing. A common method is to use attribute or word vectors as a priori category features (auxiliary information) and complete the domain transfer from training of seen classes to recognition of unseen classes by building a mapping between image features and a priori category features. However, feature extraction of the whole image lacks discrimination, and the amount of information of single attribute features or word vector features of categories is insufficient, which makes the matching degree between image features and prior class features not high and affects the accuracy of the ZSIC model. To this end, a spatial attention mechanism is designed, and an image feature extraction module based on this attention mechanism is constructed to screen critical features with discrimination. A semantic information fusion method based on matrix decomposition is proposed, which first decomposes the attribute features and then fuses them with the extracted word vector features of a dataset to achieve information expansion. Through the above two improvement measures, the classification accuracy of the ZSIC model for unseen images is improved. The experimental results on public datasets verify the effect and superiority of the proposed methods.

16.
Plant J ; 106(1): 159-173, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33421204

RESUMEN

The phytohormone cytokinin plays a significant role in nearly all aspects of plant growth and development. Cytokinin signaling has primarily been studied in the dicot model Arabidopsis, with relatively little work done in monocots, which include rice (Oryza sativa) and other cereals of agronomic importance. The cytokinin signaling pathway is a phosphorelay comprised of the histidine kinase receptors, the authentic histidine phosphotransfer proteins (AHPs) and type-B response regulators (RRs). Two negative regulators of cytokinin signaling have been identified: the type-A RRs, which are cytokinin primary response genes, and the pseudo histidine phosphotransfer proteins (PHPs), which lack the His residue required for phosphorelay. Here, we describe the role of the rice PHP genes. Phylogenic analysis indicates that the PHPs are generally first found in the genomes of gymnosperms and that they arose independently in monocots and dicots. Consistent with this, the three rice PHPs fail to complement an Arabidopsis php mutant (aphp1/ahp6). Disruption of the three rice PHPs results in a molecular phenotype consistent with these elements acting as negative regulators of cytokinin signaling, including the induction of a number of type-A RR and cytokinin oxidase genes. The triple php mutant affects multiple aspects of rice growth and development, including shoot morphology, panicle architecture, and seed fill. In contrast to Arabidopsis, disruption of the rice PHPs does not affect root vascular patterning, suggesting that while many aspects of key signaling networks are conserved between monocots and dicots, the roles of at least some cytokinin signaling elements are distinct.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Citocininas/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Oryza/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética
17.
Bioorg Med Chem ; 74: 117052, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36288657

RESUMEN

Three types of 2-arylamino-4-(piperidin-4-yloxy)pyrimidines (I-III) were designed and synthesized as covalent EGFR(epidermal growth factor receptor)T790M/L858R inhibitors by replacement of the common reported 4-(3-amino)phenoxyl moiety with 4-(4-hydroxy)piperidine-4-oxyl, and the introduction of fused-thiophene or -pyrrole on the pyrimidine core to strategically achieve conformational restriction. According to our biological evaluation, it was found that compound 9i could potently suppress EGFRT790M/L858R kinase and H1975 cell proliferation, with IC50 values of 4.902 nM and 0.6210 µM, respectively. Further study showed that 9i not only demonstrated highly selective inhibitory effects toward EGFRT790M/L858R over wild-type EGFR (EGFRWT), but it also had low cytotoxicity against normal HBE(human bronchial epithelial) and L-02 cells. Action mechanism studies showed that 9i effectively hindered cell migration and promoted apoptosis by AO(Acridine Orange)/EB(Ethidium Bromide) staining. These data would provide important clues for the screening of novel covalent EGFRT790M/L858R inhibitors for non-small cell lung cancer (NSCLC) treatment.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Receptores ErbB , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Inhibidores de Proteínas Quinasas , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Línea Celular Tumoral , Mutación , Pirimidinas , Proliferación Celular
18.
Sensors (Basel) ; 22(15)2022 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-35898032

RESUMEN

With the wide application of social media, public opinion analysis in social networks has been unable to be met through text alone because the existing public opinion information includes data information of various modalities, such as voice, text, and facial expressions. Therefore multi-modal emotion analysis is the current focus of public opinion analysis. In addition, multi-modal emotion recognition of speech is an important factor restricting the multi-modal emotion analysis. In this paper, the emotion feature retrieval method for speech is firstly explored and the processing method of sample disequilibrium data is then analyzed. By comparing and studying the different feature fusion methods of text and speech, respectively, the multi-modal feature fusion method for sample disequilibrium data is proposed to realize multi-modal emotion recognition. Experiments are performed using two publicly available datasets (IEMOCAP and MELD), which shows that processing multi-modality data through this method can obtain good fine-grained emotion recognition results, laying a foundation for subsequent social public opinion analysis.


Asunto(s)
Opinión Pública , Voz , Emociones , Expresión Facial , Humanos , Red Social
19.
Nano Lett ; 21(13): 5859-5866, 2021 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-34152779

RESUMEN

RNA interference, which involves the delivery of small interfering RNA (siRNA), has been used to validate target genes, to understand and control cellular metabolic pathways, and to use as a "green" alternative to confer pest tolerance in crops. Conventional siRNA delivery methods such as viruses and Agrobacterium-mediated delivery exhibit plant species range limitations and uncontrolled DNA integration into the plant genome. Here, we synthesize polyethylenimine-functionalized gold nanoclusters (PEI-AuNCs) to mediate siRNA delivery into intact plants and show that these nanoclusters enable efficient gene knockdown. We further demonstrate that PEI-AuNCs protect siRNA from RNase degradation while the complex is small enough to bypass the plant cell wall. Consequently, AuNCs enable gene knockdown with efficiencies of up 76.5 ± 5.9% and 76.1 ± 9.5% for GFP and ROQ1, respectively, with no observable toxicity. Our data suggest that AuNCs can deliver siRNA into intact plant cells for broad applications in plant biotechnology.


Asunto(s)
Oro , Células Vegetales , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Polietileneimina , ARN Interferente Pequeño/genética
20.
Rheumatology (Oxford) ; 60(3): 1392-1399, 2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-32974683

RESUMEN

OBJECTIVE: To assess the association between meniscal volume, its change over time and the development of knee OA after 30 months in overweight/obese women. METHODS: Data from the PRevention of knee Osteoarthritis in Overweight Females study were used. This cohort included 407 women with a BMI ≥ 27 kg/m2, free of OA-related symptoms. The primary outcome measure was incident OA after 30 months, defined by one out of the following criteria: medial or lateral joint space narrowing (JSN) ≥ 1.0 mm, incident radiographic OA [Kellgren and Lawrence (K&L) ≥ 2], or incident clinical OA. The secondary outcomes were either of these items separately. Menisci at both baseline and follow-up were automatically segmented to obtain meniscal volume and delta-volumes. Generalized estimating equations were used to evaluate associations between the volume measures and the outcomes. RESULTS: Medial and lateral baseline and delta-volumes were not significantly associated to the primary outcome. Lateral meniscal baseline volume was significantly associated to lateral JSN [odds ratio (OR) = 0.87; 95% CI: 0.75, 0.99], while other measures were not. Medial and lateral baseline volume were positively associated to K&L incidence (OR = 1.32 and 1.22; 95% CI: 1.15, 1.50 and 1.03, 1.45, respectively), while medial and lateral delta-volume were negatively associated to K&L incidence (OR = 0.998 and 0.997; 95% CI: 0.997, 1.000 and 0.996, 0.999, respectively). None of the meniscal measures were significantly associated to incident clinical OA. CONCLUSION: Larger baseline meniscal volume and the decrease of meniscal volume over time were associated to the development of structural OA after 30 months in overweight and obese women.


Asunto(s)
Menisco/patología , Osteoartritis de la Rodilla/etiología , Artrografía , Índice de Masa Corporal , Femenino , Humanos , Imagen por Resonancia Magnética , Menisco/diagnóstico por imagen , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/patología , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/patología , Sobrepeso/complicaciones , Sobrepeso/patología
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