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1.
J Cell Commun Signal ; 18(2): e12021, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38946718

RESUMEN

lncRNA ZFAS1 was identified to facilitate thyroid cancer, but its role in medullary thyroid carcinoma (MTC) remains unknown. This study aimed to unravel the potential function of this lncRNA in MTC by investigating the involvement of the lncRNA ZFAS1 in a ceRNA network that regulates MTC invasion. Proliferation, invasion, and migration of cells were evaluated using EdU staining and Transwell assays. Immunoprecipitation (IP) assays, dual-fluorescence reporter, and RNA IP assays were employed to examine the binding interaction among genes. Nude mice were used to explore the role of lncRNA ZFAS1 in MTC in vivo. ZFAS1 and EPAS1 were upregulated in MTC. Silencing ZFAS1 inhibited MTC cell proliferation and invasion under hypoxic conditions, which reduced EPAS1 protein levels. UCHL1 knockdown increased EPAS1 ubiquitination. ZFAS1 positively regulated UCHL1 expression by binding to miR-214-3p. Finally, silencing ZFAS1 significantly repressed tumor formation and metastasis in MTC. LncRNA ZFAS1 promotes invasion of MTC by upregulating EPAS1 expression via the miR-214-3p/UCHL1 axis.

2.
BMC Neurol ; 24(1): 179, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802755

RESUMEN

BACKGROUND: Accumulating neuroimaging evidence indicates that patients with cervical dystonia (CD) have changes in the cortico-subcortical white matter (WM) bundle. However, whether these patients' WM structural networks undergo reorganization remains largely unclear. We aimed to investigate topological changes in large-scale WM structural networks in patients with CD compared to healthy controls (HCs), and explore the network changes associated with clinical manifestations. METHODS: Diffusion tensor imaging (DTI) was conducted in 30 patients with CD and 30 HCs, and WM network construction was based on the BNA-246 atlas and deterministic tractography. Based on the graph theoretical analysis, global and local topological properties were calculated and compared between patients with CD and HCs. Then, the AAL-90 atlas was used for the reproducibility analyses. In addition, the relationship between abnormal topological properties and clinical characteristics was analyzed. RESULTS: Compared with HCs, patients with CD showed changes in network segregation and resilience, characterized by increased local efficiency and assortativity, respectively. In addition, a significant decrease of network strength was also found in patients with CD relative to HCs. Validation analyses using the AAL-90 atlas similarly showed increased assortativity and network strength in patients with CD. No significant correlations were found between altered network properties and clinical characteristics in patients with CD. CONCLUSION: Our findings show that reorganization of the large-scale WM structural network exists in patients with CD. However, this reorganization is attributed to dystonia-specific abnormalities or hyperkinetic movements that need further identification.


Asunto(s)
Imagen de Difusión Tensora , Tortícolis , Sustancia Blanca , Humanos , Tortícolis/diagnóstico por imagen , Tortícolis/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Femenino , Masculino , Imagen de Difusión Tensora/métodos , Persona de Mediana Edad , Adulto , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/patología , Anciano
3.
BMC Neurol ; 24(1): 174, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789945

RESUMEN

BACKGROUND: The thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD); however, the nature of alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD. METHODS: Structural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analysed in patients with iCD. RESULTS: Compared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group. CONCLUSION: This study highlights the neurobiological mechanisms of iCD related to thalamic volume changes.


Asunto(s)
Imagen por Resonancia Magnética , Tálamo , Tortícolis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Tortícolis/diagnóstico por imagen , Tortícolis/patología , Imagen por Resonancia Magnética/métodos , Tálamo/diagnóstico por imagen , Tálamo/patología , Adulto , Anciano , Núcleos Talámicos/diagnóstico por imagen , Núcleos Talámicos/patología
4.
Brain Commun ; 6(2): fcae117, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638150

RESUMEN

The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.

5.
J Med Chem ; 67(6): 4624-4640, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38483132

RESUMEN

Dynemicin A has been the sole prototypical anthraquinone-fused enediyne (AFE) explored since its discovery in 1989. This study investigates the distinct DNA binding and cleavage mechanisms of emerging AFEs, represented by tiancimycins and yangpumicins, along with semisynthetic analogues. Our findings reveal their potent cytotoxicity against various tumor cell lines, while 18-methoxy tiancimycin A treatment could significantly suppress breast tumor growth with minimal toxicity. One of the most potent AFEs, i.e., tiancimycin A, preferentially targets DNA sequences 5'-ATT, 5'-CTT, 5'-GAA, 5'-GAT, and 5'-TTA. Molecular dynamics simulations suggest that emerging AFEs intercalate deeper into AT-rich DNA base pairs compared to dynemicin A. Importantly, tiancimycin A may equilibrate between insertional and intercalative modes without deintercalation, enabling selective cleavage of T and A bases. This study underscores how subtle structural variations among AFEs significantly influence their DNA recognition and cleavage, facilitating future design of novel AFEs as potent and selective payloads for antibody-drug conjugates.


Asunto(s)
ADN , Enediinos , Enediinos/química , Antraquinonas/química , Antibióticos Antineoplásicos/química
6.
BMC Public Health ; 24(1): 64, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166746

RESUMEN

BACKGROUND: Discharged psychiatric patients are at higher risk of suicide due to various risk factors in their lives compared to the general population. However, specific problems and needs of these patients after discharge remain unclear. This research constitutes a segment of a broader implementation study designed to formulate an interventional strategy targeting post-discharge suicide among Chinese psychiatric patients. The present study seeks to qualitatively investigate the problems and needs from the perspectives of patients, their lay healthcare supporters (LHSs), and mental health professionals (MPs), aiming to enhance the efficacy of the interventional strategy. METHODS: This study is part of a larger implementation study based on Shenzhen Kangning Hospital (SKH) in Shenzhen, Guangdong, China. Under the community-based participatory research framework, we recruited discharged psychiatric patients, their LHSs, and MPs as a collaborative community team, and we conducted individual in-depth interviews for patients and LSHs and focus group interviews with MPs. We utilized a thematic analysis approach to identify sub-themes and themes from interviews through systematically coding and analyzing the data. RESULTS: A total of 45 participants were recruited for interviews, comprising 17 patients, 8 LHSs, and 20 MPs. We conducted 25 individual in-depth interviews and 3 focus group interviews. Through the interviews, we identified three themes of post-discharge problems: problems related to self, family-related problems, societal and community-related problems. We also identified four themes related to reducing post-discharge suicide: proactive self-management, multifunctional relatives, multifunctional MP group, and a warm society. The tangible support from LHSs and emotional support from MPs are strongly emphasized. Follow-up interventions were identified as the most significant way to addressing these unmet needs. Instrumental support from the community and a caring and non-discriminatory environment for individuals with mental disorders are essential for reducing suicide risk. CONCLUSIONS: Establishing an integrated mental health care service network that connects psychiatric patients, LHSs, and MPs cross community and societal sectors, with patient-centered follow-up care at its core, is a practical approach to better address patients' needs and reduce post-discharge suicide. TRIAL REGISTRATION: Registration number: NCT04907669. Date of registration: May 26th,2021.


Asunto(s)
Suicidio , Humanos , Alta del Paciente , Cuidados Posteriores , Salud Mental , Atención a la Salud , Investigación Cualitativa
7.
Environ Sci Technol ; 58(6): 2615-2626, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38291963

RESUMEN

The large-scale and cross-regional payment for ecosystem services (PES) contributes positively to ecology-economy balance and thus helps prevent environmental challenges such as "sand storm". However, existing PES programs often overlook the connection between service-providing areas (SPAs) and service-benefiting areas (SBAs). Here, we developed an interregional PES framework based on the theory of ecosystem services flow and applied it to the largest Chinese grassland nature reserve, Xilingol Prairie, to quantitatively identify SPAs, SBAs, and flow paths of the ecosystem wind erosion prevention service (WEPS). We showed that, from 2000 to 2020, the grassland ecosystem of Xilingol Prairie had brought an annual WEPS benefit of 1.21 × 108 t/a and economic value of 12.44 × 108 CNY/a, accounting for approximately 107.71% of the GDP in the same area and year and with a slightly increasing trend in most areas. We reveal obvious seasonal (over half in the spring) and interannual variations in the benefit and that Inner Mongolia, Hebei, and Northeast China are the most important beneficiaries of WEPS, rather than Beijing and Tianjin as traditionally thought. Our results warn that the WEPS supply capacity will not last long and call for finer spatial (e.g., among cities) and temporal (e.g., focus on the spring) resolution for PES policy design.


Asunto(s)
Ecosistema , Viento , Pradera , Conservación de los Recursos Naturales , China
8.
Appl Microbiol Biotechnol ; 108(1): 18, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38170317

RESUMEN

Exploration of high-yield mechanism is important for further titer improvement of valuable antibiotics, but how to achieve this goal is challenging. Tiancimycins (TNMs) are anthraquinone-fused enediynes with promising drug development potentials, but their prospective applications are limited by low titers. This work aimed to explore the intrinsic high-yield mechanism in previously obtained TNMs high-producing strain Streptomyces sp. CB03234-S for the further titer amelioration of TNMs. First, the typical ribosomal RpsL(K43N) mutation in CB03234-S was validated to be merely responsible for the streptomycin resistance but not the titer improvement of TNMs. Subsequently, the combined transcriptomic, pan-genomic and KEGG analyses revealed that the significant changes in the carbon and amino acid metabolisms could reinforce the metabolic fluxes of key CoA precursors, and thus prompted the overproduction of TNMs in CB03234-S. Moreover, fatty acid metabolism was considered to exert adverse effects on the biosynthesis of TNMs by shunting and reducing the accumulation of CoA precursors. Therefore, different combinations of relevant genes were respectively overexpressed in CB03234-S to strengthen fatty acid degradation. The resulting mutants all showed the enhanced production of TNMs. Among them, the overexpression of fadD, a key gene responsible for the first step of fatty acid degradation, achieved the highest 21.7 ± 1.1 mg/L TNMs with a 63.2% titer improvement. Our studies suggested that comprehensive bioinformatic analyses are effective to explore metabolic changes and guide rational metabolic reconstitution for further titer improvement of target products. KEY POINTS: • Comprehensive bioinformatic analyses effectively reveal primary metabolic changes. • Primary metabolic changes cause precursor enrichment to enhance TNMs production. • Strengthening of fatty acid degradation further improves the titer of TNMs.


Asunto(s)
Antibacterianos , Streptomyces , Antibacterianos/metabolismo , Streptomyces/metabolismo , Estreptomicina/farmacología , Perfilación de la Expresión Génica , Ácidos Grasos/metabolismo , Ingeniería Metabólica/métodos
9.
Biomacromolecules ; 24(11): 5381-5393, 2023 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-37908117

RESUMEN

A major challenge to make use of lignin as an antimicrobial material is the weak antimicrobial activity of industrial lignin. Inspired by the antimicrobial mechanism of actions of antimicrobial peptides, alkyldiamines were employed as lysine mimics for lignin modifications. Accordingly, aminoalkyl-modified lignins with different degrees of substitution of amino groups and different hydrophobicity were synthesized. The chemical structure, properties, and antimicrobial activities of the as-prepared aminoalkyl lignins were thoroughly characterized with state-of-the-art technologies. The results indicated that aminobutyl lignin showed enhanced antimicrobial activity against S. aureus and E. coli and performed even better than copper ions. The antimicrobial mechanism of action of the as-prepared aminobutyl lignin was similar to that of polylysine, which damaged the cell membrane, leading to the leakage of intracellular molecules and death of the cell. This study provides a feasible approach to afford modified lignin with enhanced antimicrobial performance, which would facilitate the high-value valorization of lignin as biological materials.


Asunto(s)
Péptidos Antimicrobianos , Lignina , Lignina/farmacología , Lignina/química , Escherichia coli , Staphylococcus aureus
10.
Neuroscience ; 531: 50-59, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37709002

RESUMEN

Selective impairment in recognizing facial expressions of disgust was reported in patients with focal dystonia several years ago, but the basic neural mechanisms remain largely unexplored. Therefore, we investigated whether dysfunction of the brain network involved in disgust recognition processing was related to this selective impairment in blepharospasm. Facial emotion recognition evaluations and resting-state functional magnetic resonance imaging were performed in 33 blepharospasm patients and 33 healthy controls (HCs). The disgust processing network was constructed, and modularity analyses were performed to identify sub-networks. Regional functional indexes and intra- and inter-functional connections were calculated and compared between the groups. Compared to HCs, blepharospasm patients demonstrated a worse performance in disgust recognition. In addition, functional connections within the sub-network involved in perception processing rather than recognition processing of disgust were significantly decreased in blepharospasm patients compared to HCs. Specifically, decreased functional connections were noted between the left fusiform gyrus (FG) and right middle occipital gyrus (MOG), the left FG and right FG, and the right FG and left MOG. We identified decreased functional activity in these regions, as indicated by a lower amplitude of low-frequency fluctuation in the left MOG, fractional amplitude of low-frequency fluctuation in the right FG, and regional homogeneity in the right FG and left MOG in blepharospasm patients versus HCs. Our results suggest that dysfunctions of the disgust processing network exist in blepharospasm. A deficit in disgust emotion recognition may be attributed to disturbances in the early perception of visual disgust stimuli in blepharospasm patients.


Asunto(s)
Blefaroespasmo , Reconocimiento Facial , Humanos , Blefaroespasmo/diagnóstico por imagen , Emociones , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Mapeo Encefálico , Expresión Facial
11.
iScience ; 26(9): 107610, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37664597

RESUMEN

GFR reaches a new baseline, primarily correlating with nephron-mass preservation, 1-12 months after partial nephrectomy (PN). However, does the ipsilateral GFR experience subsequent decline, and does acute ischemic injury has long-term effect on the operated kidney? 319 patients with two kidneys and unilateral clamped PN were analyzed. All had preoperative, new-baseline, and latest follow-up imaging/serum creatinine levels. Annual ipsilateral GFR decline rate (AIGDR) was defined as new-baseline GFR minus latest follow-up GFR normalized by new-baseline GFR, per year. Spectrum score was used to reflect the degree of acute ischemic injury in the operated kidney. 100 subjects searching for health screening served as controls. Predictive factors for AIGDR were assessed. The median AIGDR was 2.25%, significantly higher than controls (0.88%, p = 0.036). With some contralateral hypertrophy, the global annual GFR decline was similar to that of controls (0.81% vs. 0.88%, p = 0.7). Spectrum score correlated significantly with AIGDR (p = 0.037). These results support that acute ischemic injury has long-term effect on the operated kidney.

12.
Sci Adv ; 9(32): eadf3166, 2023 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-37556542

RESUMEN

The impact of atmospheric vapor pressure deficit (VPD) on plant photosynthesis has long been acknowledged, but large interactions with air temperature (T) and soil moisture (SM) still hinder a complete understanding of the influence of VPD on vegetation production across various climate zones. Here, we found a diverging response of productivity to VPD in the Northern Hemisphere by excluding interactive effects of VPD with T and SM. The interactions between VPD and T/SM not only offset the potential positive impact of warming on vegetation productivity but also amplifies the negative effect of soil drying. Notably, for high-latitude ecosystems, there occurs a pronounced shift in vegetation productivity's response to VPD during the growing season when VPD surpasses a threshold of 3.5 to 4.0 hectopascals. These results yield previously unknown insights into the role of VPD in terrestrial ecosystems and enhance our comprehension of the terrestrial carbon cycle's response to global warming.


Asunto(s)
Clima , Ecosistema , Presión de Vapor , Estaciones del Año , Suelo
13.
ACS Appl Mater Interfaces ; 15(29): 35251-35260, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37433129

RESUMEN

In the study to improve the light absorption range and intensity of dye sensitizers in the visible region and promote their photovoltaic performance, five novel polymeric metal complexes with sulfur coordination (BDTT-VBT-Ni, BDTT-VBT-Cu, BDTT-VBT-Zn, BDTT-VBT-Cd, and BDTT-VBT-Hg) to be used as D-A-π-A motif dye sensitizers were designed, synthesized, and characterized. In these polymeric metal complexes with sulfur coordination, the metal complexes with sulfur coordination of benzodithiophene derivatives are used as auxiliary electron acceptors, 8-quinolinol derivatives are used as π-bridge and electron acceptors, and thienylbenzene-[1,2-b:4,5-b'] dithiophene (BDTT) are used as electron donors. The effect of different metal complexes with sulfur coordination on the photovoltaic performance of dye sensitizers has been systematically studied. Under AM 1.5 irradiation (100 mW cm-2), the devices of dye-sensitized solar cells (DSSCs) based on five polymeric metal complexes with sulfur coordination exhibited a short-circuit current density (Jsc) of 13.43, 15.07, 18.00, 18.99, and 20.78 mA cm-2, respectively, and their power conversion efficiencies (PCEs) were 7.10, 8.59, 10.68, 11.23, and 12.89%, respectively, and their thermal decomposition temperatures (Td) were 251, 257, 265, 276, and 277 °C, respectively. The result shows that the Jsc and PCE of five polymeric metal complexes increase by degrees, and the PCE of BDTT-VBT-Hg is up to 12.89%, which is because of the strength of the coordination bonds between Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) and sulfur increases in turn so that the electron-withdrawing ability and electron-transfer ability of auxiliary electron acceptors is enhanced. These results provide a new way to develop stable and efficient metal complexes with sulfur coordination dye sensitizers in the future.

14.
Anal Chem ; 95(26): 9797-9804, 2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37327388

RESUMEN

DNA aptamers are single-stranded DNA oligonucleotide sequences that bind to specific targets with high affinity. Currently, DNA aptamers can be produced only by in vitro synthesis. It is difficult for DNA aptamers to have a sustained impact on intracellular protein activity, which limits their clinical application. In this study, we developed a DNA aptamer expression system to generate DNA aptamers with functional activity in mammalian cells by mimicking retroviruses. Using this system, DNA aptamers targeting intracellular Ras (Ra1) and membrane-bound CD71 (XQ2) were successfully generated in cells. In particular, the expressed Ra1 not only specifically bound to the intracellular Ras protein but also inhibited the phosphorylation of downstream ERK1/2 and AKT. Furthermore, by inserting the DNA aptamer expression system for Ra1 into a lentivirus vector, the system can be delivered into cells and stably produce Ra1 over time, resulting in the inhibition of lung cancer cell proliferation. Therefore, our study provides a novel strategy for the intracellular generation of DNA aptamers with functional activity and opens a new avenue for the clinical application of intracellular DNA aptamers in disease treatment.


Asunto(s)
Aptámeros de Nucleótidos , Animales , Aptámeros de Nucleótidos/genética , Retroviridae/genética , ADN de Cadena Simple , Lentivirus/genética , Técnica SELEX de Producción de Aptámeros/métodos , Mamíferos
15.
Plant J ; 115(2): 398-413, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37021636

RESUMEN

The potato's most devastating disease is late blight, which is caused by Phytophthora infestans. Whereas various resistance (R) genes are known, most are typically defeated by this fast-evolving oomycete pathogen. However, the broad-spectrum and durable R8 is a vital gene resource for potato resistance breeding. To support an educated deployment of R8, we embarked on a study on the corresponding avirulence gene Avr8. We overexpressed Avr8 by transient and stable transformation, and found that Avr8 promotes colonization of P. infestans in Nicotiana benthamiana and potato, respectively. A yeast-two-hybrid (Y2H) screen showed that AVR8 interacts with a desumoylating isopeptidase (StDeSI2) of potato. We overexpressed DeSI2 and found that DeSI2 positively regulates resistance to P. infestans, while silencing StDeSI2 downregulated the expression of a set of defense-related genes. By using a specific proteasome inhibitor, we found that AVR8 destabilized StDeSI2 through the 26S proteasome and attenuated early PTI responses. Altogether, these results indicate that AVR8 manipulates desumoylation, which is a new strategy that adds to the plethora of mechanisms that Phytophthora exploits to modulate host immunity, and StDeSI2 provides a new target for durable resistance breeding against P. infestans in potato.


Asunto(s)
Phytophthora infestans , Solanum tuberosum , Fitomejoramiento , Inmunidad de la Planta , Solanum tuberosum/genética , Enfermedades de las Plantas
16.
Genes (Basel) ; 14(4)2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-37107592

RESUMEN

Functional linear regression models have been widely used in the gene association analysis of complex traits. These models retain all the genetic information in the data and take full advantage of spatial information in genetic variation data, which leads to brilliant detection power. However, the significant association signals identified by the high-power methods are not all the real causal SNPs, because it is easy to regard noise information as significant association signals, leading to a false association. In this paper, a method based on the sparse functional data association test (SFDAT) of gene region association analysis is developed based on a functional linear regression model with local sparse estimation. The evaluation indicators CSR and DL are defined to evaluate the feasibility and performance of the proposed method with other indicators. Simulation studies show that: (1) SFDAT performs well under both linkage equilibrium and linkage disequilibrium simulation; (2) SFDAT performs successfully for gene regions (including common variants, low-frequency variants, rare variants and mix variants); (3) With power and type I error rates comparable to OLS and Smooth, SFDAT has a better ability to handle the zero regions. The Oryza sativa data set is analyzed by SFDAT. It is shown that SFDAT can better perform gene association analysis and eliminate the false positive of gene localization. This study showed that SFDAT can lower the interference caused by noise while maintaining high power. SFDAT provides a new method for the association analysis between gene regions and phenotypic quantitative traits.


Asunto(s)
Variación Genética , Modelos Lineales , Estudios de Asociación Genética , Fenotipo , Simulación por Computador
17.
Acta Radiol ; 64(6): 2118-2125, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36912041

RESUMEN

BACKGROUND: Field-of-view optimized and constrained undistorted single-shot imaging (FOCUS) is a new sequence that shows enhanced anatomical details, improving the diffusion-weighted (DW) images. PURPOSE: To investigate the value of FOCUS diffusion-weighted imaging (DWI) in the evaluation of nasopharyngeal carcinoma (NPC) and compare it with the single-shot echo planner imaging (SS-EPI) DWI approach. MATERIAL AND METHODS: A total of 87 patients with NPC underwent magnetic resonance imaging, including FOCUS and SS-EPI DWI sequences. The signal-to-noise ratio (SNR), signal-intensity ratio (SIR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values of the nasopharyngeal lesions were measured and compared. According to the clinical stages of patients, T and N were divided into early and advanced stage groups, respectively. The mean ADC values of the two techniques were computed, and the area under the curve (AUC) was estimated to calculate the diagnostic efficiency. RESULTS: Subjective and objective image qualitative values of FOCUS were significantly higher than those of SS-EPI. The ADC values for FOCUS of early T and N stages were significantly lower than those of the advanced stages. CONCLUSION: FOCUS provides significantly better image quality in NPC compared to SS-EPI, with lower ADC values for early-stage disease than late-stage disease.


Asunto(s)
Imagen Eco-Planar , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Imagen Eco-Planar/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética , Relación Señal-Ruido , Neoplasias Nasofaríngeas/diagnóstico por imagen , Reproducibilidad de los Resultados
18.
Genet Sel Evol ; 55(1): 17, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36932324

RESUMEN

BACKGROUND: Dairy cattle production systems are mostly based on purebreds, but recently the use of crossbreeding has received increased interest. For genetic evaluations including crossbreds, several methods based on single-step genomic best linear unbiased prediction (ssGBLUP) have been proposed, including metafounder ssGBLUP (MF-ssGBLUP) and breed-specific ssGBLUP (BS-ssGBLUP). Ideally, models that account for breed effects should perform better than simple models, but knowledge on the performance of these methods is lacking for two-way crossbred cattle. In addition, the differences in the estimates of genetic parameters (such as the genetic variance component and heritability) between these methods have rarely been investigated. Therefore, the aims of this study were to (1) compare the estimates of genetic parameters for average daily gain (ADG) and feed conversion ratio (FCR) between these methods; and (2) evaluate the impact of these methods on the predictive ability for crossbred performance. METHODS: Bivariate models using standard ssGBLUP, MF-ssGBLUP and BS-ssGBLUP for the genetic evaluation of ADG and FCR were investigated. To measure the predictive ability of these three methods, we estimated four estimators, bias, dispersion, population accuracy and ratio of population accuracies, using the linear regression (LR) method. RESULTS: The results show that, for both ADG and FCR, the heritabilities were low with the three methods. For FCR, the differences in the estimated genetic parameters were small between the three methods, while for ADG, those estimated with BS-ssGBLUP deviated largely from those estimated with the other two methods. Bias and dispersion were similar across the three methods. Population accuracies for both ADG and FCR were always higher with MF-ssGBLUP than with ssGBLUP, while with BS-ssGBLUP the population accuracy was highest for FCR and lowest for ADG. CONCLUSIONS: Our results indicate that in the genetic evaluation for crossbred performance in a two-way crossbred cattle production system, the predictive ability of MF-ssGBLUP and BS-ssGBLUP is greater than that of ssGBLUP, when the estimated variance components are consistent across the three methods. Compared with BS-ssGBLUP, MF-ssGBLUP is more robust in its superiority over ssGBLUP.


Asunto(s)
Genoma , Modelos Genéticos , Bovinos/genética , Animales , Genómica/métodos , Hibridación Genética , Polimorfismo de Nucleótido Simple , Genotipo , Fenotipo
19.
Environ Pollut ; 327: 121509, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36967005

RESUMEN

Ground-level fine particulate matter (PM2.5) and ozone (O3) are air pollutants that can pose severe health risks. Surface PM2.5 and O3 concentrations can be monitored from satellites, but most retrieval methods retrieve PM2.5 or O3 separately and disregard the shared information between the two air pollutants, for example due to common emission sources. Using surface observations across China spanning 2014-2021, we found a strong relationship between PM2.5 and O3 with distinct spatiotemporal characteristics. Thus, in this study, we propose a new deep learning model called the Simultaneous Ozone and PM2.5 inversion deep neural Network (SOPiNet), which allows for daily real-time monitoring and full coverage of PM2.5 and O3 simultaneously at a spatial resolution of 5 km. SOPiNet employs the multi-head attention mechanism to better capture the temporal variations in PM2.5 and O3 based on previous days' conditions. Applying SOPiNet to MODIS data over China in 2022, using 2019-2021 to construct the network, we found that simultaneous retrievals of PM2.5 and O3 improved the performance compared with retrieving them independently: the temporal R2 increased from 0.66 to 0.72 for PM2.5, and from 0.79 to 0.82 for O3. The results suggest that near-real time satellite-based air quality monitoring can be improved by simultaneous retrieval of different but related pollutants. The codes of SOPiNet and its user guide are freely available online at https://github.com/RegiusQuant/ESIDLM.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Aprendizaje Profundo , Ozono , Ozono/análisis , Monitoreo del Ambiente/métodos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Contaminación del Aire/análisis , China
20.
Mater Today Bio ; 18: 100520, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36590981

RESUMEN

Lignin is a natural aromatic polymer of p-hydroxyphenylpropanoids with various biological activities. Noticeably, plants have made use of lignin as biocides to defend themselves from pathogen microbial invasions. Thus, the use of isolated lignin as environmentally benign antimicrobial is believed to be a promising high value approach for lignin valorization. On the other hand, as green and sustainable product of plant photosynthesis, lignin should be beneficial to reduce the carbon footprint of antimicrobial industry. There have been many reports that make use of lignin to prepare antimicrobials for different applications. However, lignin is highly heterogeneous polymers different in their monomers, linkages, molecular weight, and functional groups. The structure and property relationship, and the mechanism of action of lignin as antimicrobial remains ambiguous. To show light on these issues, we reviewed the publications on lignin chemistry, antimicrobial activity of lignin models and isolated lignin and associated mechanism of actions, approaches in synthesis of lignin with improved antimicrobial activity, and the applications of lignin as antimicrobial in different fields. Hopefully, this review will help and inspire researchers in the preparation of lignin antimicrobial for their applications.

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