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1.
Ital J Pediatr ; 50(1): 87, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38659062

RESUMO

The Peabody Developmental Motor Scales-2 (PDMS-2) has been used to assess the gross and fine motor skills of children (0-6 years); however, the measurement properties of the PDMS-2 are inconclusive. Here, we aimed to systematically review the measurement properties of PDMS-2, and synthesize the quality of evidence using the Consensus-based Standards for the Selection of Health Measurements Instruments (COSMIN) methodology. Electronic databases, including PubMed, EMBASE, Web of Science, CINAHL and MEDLINE, were searched for relevant studies through January 2023; these studies used PDMS-2. The methodological quality of each study was assessed by the COSMIN risk-of-bias checklist, and the measurement properties of PDMS-2 were evaluated by the COSMIN quality criteria. Modified GRADE was used to evaluate the quality of the evidence. We included a total of 22 articles in the assessment. Among the assessed measurement properties, the content validity of PDMS-2 was found to be sufficient with moderate-quality evidence. The structural validity, internal consistency, test-retest reliability and interrater reliability of the PDMS-2 were sufficient for high-quality evidence, while the intrarater reliability was sufficient for moderate-quality evidence. Sufficient high-quality evidence was also found for the measurement error of PDMS-2. The overall construct validity of the PDMS-2 was sufficient but showed inconsistent quality of evidence. The responsiveness of PDMS-2 appears to be sufficient with low-quality evidence. Our findings demonstrate that the PDMS-2 has sufficient content validity, structural validity, internal consistency, reliability and measurement error with moderate to high-quality evidence. Therefore, PDMS-2 is graded as 'A' and can be used in motor development research and clinical settings.


Assuntos
Destreza Motora , Humanos , Pré-Escolar , Criança , Reprodutibilidade dos Testes , Lactente , Destreza Motora/fisiologia , Desenvolvimento Infantil/fisiologia , Recém-Nascido , Psicometria
2.
Metabolites ; 14(4)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38668344

RESUMO

Rhubarb (RR), Chinese name Dahuang, is commonly used in the treatment of ischemic stroke (IS). However, its potential mechanism is not fully elucidated. This study intended to verify the effect of RR on IS and investigate the possible mechanism of RR in preventing IS. IS in male rats was induced by embolic middle cerebral artery occlusion (MCAO) surgery, and drug administration was applied half an hour before surgery. RR dramatically decreased the neurological deficit scores, the cerebral infarct volume, and the cerebral edema rate, and improved the regional cerebral blood flow (rCBF) and histopathological changes in the brain of MCAO rats. The 16S rRNA analysis showed the harmful microbes such as Fournierella and Bilophila were decreased, and the beneficial microbes such as Enterorhabdus, Defluviitaleaceae, Christensenellaceae, and Lachnospira were significantly increased, after RR pretreatment. 1H-nuclear magnetic resonance (1H-NMR) was used to detect serum metabolomics, and RR treatment significantly changed the levels of metabolites such as isoleucine, valine, N6-acetyllysine, methionine, 3-aminoisobutyric acid, N, N-dimethylglycine, propylene glycol, trimethylamine N-oxide, myo-inositol, choline, betaine, lactate, glucose, and lipid, and the enrichment analysis of differential metabolites showed that RR may participate in the regulation of amino acid metabolism and energy metabolism. RR exerts the role of anti-IS via regulating gut bacteria and metabolic pathways.

3.
Plant Physiol Biochem ; 210: 108589, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38593485

RESUMO

Carotenoids are important pigmented nutrients synthesized by tomato fruits during ripening. To reveal the molecular mechanism underlying carotenoid synthesis during tomato fruit ripening, we analyzed carotenoid metabolites and transcriptomes in six development stages of tomato fruits. A total of thirty different carotenoids were detected and quantified in tomato fruits from 10 to 60 DPA. Based on differential gene expression profiles and WGCNA, we explored several genes that were highly significant and negatively correlated with lycopene, all of which encode fasciclin-like arabinogalactan proteins (FLAs). The FLAs are involved in plant signal transduction, however the functional role of these proteins has not been studied in tomato. Genome-wide analysis revealed that cultivated and wild tomato species contained 18 to 22 FLA family members, clustered into four groups, and mainly evolved by means of segmental duplication. The functional characterization of FLAs showed that silencing of SlFLA1, 5, and 13 were found to contribute to the early coloration of tomato fruits, and the expression of carotenoid synthesis-related genes was up-regulated in fruits that changed phenotypically, especially in SlFLA13-silenced plants. Furthermore, the content of multiple carotenoids (including (E/Z)-phytoene, lycopene, γ-carotene, and α-carotene) was significantly increased in SlFLA13-silenced fruits, suggesting that SlFLA13 has a potential inhibitory function in regulating carotenoid synthesis in tomato fruits. The results of the present study broaden the idea of analyzing the biological functions of tomato FLAs and preliminary evidence for the inhibitory role of SlFLA13 in carotenoid synthesis in fruit, providing the theoretical basis and a candidate for improving tomato fruit quality.

5.
Chemosphere ; 354: 141720, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38493999

RESUMO

The release of organic dyes, such as Rhodamine B (RhB), into industrial wastewater has led to significant issues with color pollution in aquatic environments. Herein, we prepared a cobalt nanoparticles (NPs)-based catalyst with the nitrogen-doped carbon-support (Co@N-C) for effective PMS activation. The Co@N-C/PMS system demonstrated the excellent catalytic activity of Co@N-C for activating PMS, achieving nearly 100% degradation of RhB. Singlet oxygen (1O2) and sulfate radicals (SO4•-) were dominant reactive oxygen species for RhB degradation. Density functional theory (DFT) calculations substantiated that the production of 1O2 commenced with the initial generation of *OH through hydrogen abstraction from PMS, culminating in the direct release of oxygen to form 1O2 (PMS→*OH→O*→1O2). The generation of SO4•- was attributed to electron transfer to PMS from the surface of Co NPs (Co0→Co2+→Co3+) and the C-N shell (Co2+→Co3+). The research findings provided new insights into the development of Co-based heterogeneous catalysis for advanced oxidation of refractory organic pollutants in wastewater treatment.


Assuntos
Nanopartículas , Peróxidos , Espécies Reativas de Oxigênio , Carbono , Oxigênio
6.
Opt Lett ; 49(6): 1449-1452, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489422

RESUMO

AlGaInP-based light-emitting diodes (LEDs) suffer from a low external quantum efficiency (EQE), which is mainly restrained by the poor light extraction efficiency. Here, we demonstrate AlGaInP-based vertical miniaturized-LEDs (mini-LEDs) with a porous n-AlGaInP surface using a wet etching process to boost light extraction. We investigated the effects of etching time on the surface morphology of the porous n-AlGaInP surface. We found that as the etching time is prolonged, the density of pores increases initially and decreases subsequently. In comparison with the vertical mini-LED with a smooth n-AlGaInP surface, the vertical mini-LEDs with the porous n-AlGaInP surface reveal improvement in light output power and EQE, meanwhile, without the deterioration of electrical performance. The highest improvement of 38.9% in EQE measured at 20 mA is observed from the vertical mini-LED with the maximum density of the pores. Utilizing a three-dimensional finite-difference time-domain method, we reveal the underlying mechanisms of improved performance, which are associated with suppressed total internal reflection and efficient light scattering effect of the pores.

7.
J Hazard Mater ; 467: 133638, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38354441

RESUMO

Peracetic acid (PAA) emerges as a promising disinfectant and oxidant applied worldwide, and its application has been broadened for advanced oxidation processes (AOPs) in wastewater treatment. Current studies on transition metal-activated AOPs utilized relatively high concentrations of catalysts, leading to potential secondary pollution concerns. This study boosts the understanding of reaction mechanism in PAA activation system under a low-level concentration. Herein, trace levels of Co(II) (1 µM) and practical dosages of PAA (50-250 µM) were employed, achieving noticeable ciprofloxacin (CIP) degradation efficiencies (75.8-99.0%) within 20 min. Two orders of magnitude of the CIP's antibacterial activity significantly decreased after Co(II)/PAA AOP treatment, which suggested the effective ecological risk control capability of the reaction system. The degradation performed well in various water matrices and the primary reactive species is proposed to be CoHPO4-OO(O)CCH3 complexes with scavenging tests and electron paramagnetic resonance tests. The degradation pathway of fluoroquinolones including piperazine ring-opening (dealkylation and oxidation), defluorination, and decarboxylation, were systematically elucidated. This study boosts a comprehensive and novel understanding of PAA-based AOP for CIP degradation.


Assuntos
Ciprofloxacina , Ácido Peracético , Oxidantes , Fosfatos , Estresse Oxidativo
8.
Nutrients ; 16(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38398859

RESUMO

The aim of the study was to explore the impact of both the macronutrient composition and snacking timing on the postprandial glycemic insulinemic responses and food intake. Seventeen healthy female volunteers completed the randomized crossover trials. The volunteers were provided a standard breakfast and lunch at 8:00 and 13:00, respectively, and an ad libitum dinner at 18:00. Provided at either 10:30 (midmorning) or 12:30 (preload), the glycemic effects of the three types of 70 kcal snacks, including chicken breast (mid-C and pre-C), apple (mid-A and pre-A), and macadamia nut (mid-M and pre-M), were compared with the non-snack control (CON), evaluated by continuous glucose monitoring (CGM). The mid-M showed increased insulin resistance after lunch compared with CON, while the pre-M did not. The pre-A stabilized the glycemic response in terms of all variability parameters after lunch, while the mid-A had no significant effect on postprandial glucose control. Both the mid-C and pre-C improved the total area under the glucose curve, all glycemic variability parameters, and the insulin resistance within 2 h after lunch compared with CON. The pre-C attained the lowest energy intake at dinner, while the mid-A and the mid-M resulted in the highest. In conclusion, the chicken breast snack effectively stabilized postprandial glycemic excursion and reduced insulin resistance while the macadamia snack did not, regardless of ingestion time. Only as a preload could the apple snack mitigate the glucose response after the subsequent meal.


Assuntos
Resistência à Insulina , Lanches , Humanos , Feminino , Lanches/fisiologia , Glicemia , Voluntários Saudáveis , Automonitorização da Glicemia , Refeições , Glucose/farmacologia , Nutrientes , Período Pós-Prandial/fisiologia , Estudos Cross-Over , Insulina/farmacologia
9.
J Am Soc Mass Spectrom ; 35(2): 357-364, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38252030

RESUMO

A novel tridentate-cyclometalating Pt(IV) complex, namely, Pt(IV)(C∧N∧C)(Cl)2(DMSO), is initially synthesized through a series of reactions using Pt(II) complexes. The optoelectronic properties of Pt(IV)(C∧N∧C)(Cl)2(DMSO) are fully studied by adequate characterizations.

10.
Adv Sci (Weinh) ; 11(12): e2307165, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38225747

RESUMO

Flexible and highly ultraviolet (UV) sensitive materials garner considerable attention in wearable devices, adaptive sensors, and light-driven actuators. Herein, a type of nanofilms with unprecedented fully reversible UV responsiveness are successfully constructed. Building upon this discovery, a new system for ultra-fast, sensitive, and reliable UV detection is developed. The system operates by monitoring the displacement of photoinduced macroscopic motions of the nanofilms based composite membranes. The system exhibits exceptional responsiveness to UV light at 375 nm, achieving remarkable response and recovery times of < 0.3 s. Furthermore, it boasts a wide detection range from 2.85 µW cm-2 to 8.30 mW cm-2, along with robust durability. Qualitative UV sensing is accomplished by observing the shape changes of the composite membranes. Moreover, the composite membrane can serve as sunlight-responsive actuators for artificial flowers and smart switches in practical scenarios. The photo-induced motion is ascribed to the cis-trans isomerization of the acylhydrazone bonds, and the rapid and fully reversible shape transformation is supposed to be a synergistic result of the instability of the cis-isomers acylhydrazone bonds and the rebounding property of the networked nanofilms. These findings present a novel strategy for both quantitative and qualitative UV detection.

11.
An. bras. dermatol ; 99(1): 27-33, Jan.-Feb. 2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1527711

RESUMO

Abstract Background: Primary cutaneous CD4+ small/medium-sized pleomorphic T-Cell lymphoproliferative disorder (PC-SMTLD) has been considered as a controversial dermatological disease that has been included in cutaneous T-cell lymphoma group, presenting most commonly as a solitary nodule and/or plaque with a specific and characteristic head and neck predilection. Due to the considerable overlap between PC-SMTLD and pseudolymphoma (PL), the differential diagnosis is often challenging. Methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, it has rarely been studied in cutaneous lymphomas. Objectives: The authors aimed to explore the role of differential 5-hmC immunostaining as a useful marker to distinguish PC-SMTLD from PL. Methods: Retrospective case series study with immunohistochemical and immunofluorescence analysis of 5-hmC was performed in PL and PC-SMTLD. Results: Significant decrease of 5-hmC nuclear staining was observed in PC-SMTLD when compared with PL (p<0.0001). By semi-quantitative grade integration, there were statistical differences in the final 5-hmC scores in the two study groups. The IF co-staining of 5-hmC with CD4 revealed a decrease of 5-hmC in CD4+ lymphocytes of PC-SMTLD. Study limitations: The small clinical sample size of the study. Conclusions: The immunorreactivity of 5-hmC in CD4+ lymphocytes was highly suggestive of a benign process as PL. Furthermore, the decrease of 5-hmC nuclear staining in PC-SMTLD indicated its lymphoproliferative status and helped to make the differential diagnosis with PL. © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

12.
Nurse Educ Pract ; 75: 103874, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244336

RESUMO

AIM: To delineate the prevalence of smartphone addiction among nursing students. Further, to identify associated harms and underlying risk factors based on established theoretical models. BACKGROUND: Smartphones have become indispensable tools for students. However, excessive use can lead to smartphone addiction, causing physiological, psychological and social harm. Nursing students represent a unique population whose smartphone use may differ from other disciplines due to clinical training demands. METHODS: A scoping review was conducted following the Arksey and O'Malley framework. Seven databases were systematically searched from inception to August 2023. Inclusion criteria encompassed original research on smartphone addiction, harms and risks among nursing students. Data were extracted and thematically synthesized. RESULTS: Studies (n=39) met inclusion criteria, representing 15 countries. Rates of smartphone addiction among nursing students ranged from 19% to 72%, averaging 40-50%. Incorporated into Engel's biopsychosocial models, the harm is emphasized across individual inclinations, emotional aspects, cognitive processes and executive functions. Physiological harms include sleep disruption, vision concerns,other physiological concerns. psychologically, addiction correlated with increased anxiety and depression,decline in self-esteem, learning and attention and other psychological concerns. socially, it encompasses harms such as interpersonal relationships challenges, career development and decline in social abilities. The I-PACE model identifies various risk factors for smartphone addiction among nursing students, including personal factors such as interpersonal relationship anxiety and perceived academic pressure, affective factors like high stress and learning burnout, cognitive factors such as the need for online social interaction and low perception of social support, as well as executive factors like extended usage duration, poor self-control and usage before sleep. CONCLUSION: Smartphone addiction among nursing students presents tangible harms. A proposed theoretical model integrating established frameworks provides avenues to better comprehend addiction genesis and potential intervention strategies. Given addiction's multi-factorial nature, future research investigating harm mitigation through optimizing predisposing, precipitating and perpetuating factors is warranted.


Assuntos
Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Transtorno de Adição à Internet , Ansiedade/epidemiologia , Habilidades Sociais , Smartphone , Fatores de Risco
13.
Med Biol Eng Comput ; 62(2): 551-561, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37945796

RESUMO

Three-dimensional (3D) reconstruction of computed tomography (CT) and magnetic resonance imaging (MRI) images is an important diagnostic method, which is helpful for doctors to clearly recognize the 3D shape of the lesion and make the surgical plan. In the study of medical image reconstruction, most researchers use surface rendering or volume rendering method to construct 3D models from image sequences. The watertightness of the algorithm-reconstructed surface will be affected by the segmentation precision or the thickness of the CT layer. The articular surfaces at femoral ends are often used in biomechanical simulation experiments. The model may not conform to its original shape due to the manual repair of non-watertight surfaces. To solve this problem, a 3D reconstruction method of leg bones based on deep learning is proposed in this paper. By deforming the convex hull of the target, comparing with state-of-the-art methods, our method can stably generate a watertight model with higher reconstruction accuracy. In the situation of target transition structures getting fuzzy and the layer spacing increasing, the proposed method can maintain better reconstruction performance and appear higher robustness. Also, the chamfer loss is optimized based on the rotational shape of the leg bones, and the weight of the loss function can be assigned according to the geometric characteristics of the target. Experiment results show that the optimization method improves the accuracy of the model. Furthermore, our research provides a reference for the application of deep learning in medical image reconstruction.


Assuntos
Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Imageamento Tridimensional/métodos , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Simulação por Computador , Fêmur/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos
14.
CNS Neurosci Ther ; 30(3): e14442, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37665118

RESUMO

BACKGROUND: Post-stroke dysphagia (PSD), a common and serious disease, affects the quality of life of many patients and their families. Electroacupuncture (EA) has been commonly used effectively in the treatment of PSD, but the therapeutic mechanism is still under exploration at present. We aim to investigate the effect of the nucleus tractus solitarus (NTS) on the treatment of PSD by EA at Lianquan (CV23) through the primary motor cortex (M1). METHODS: C57 male mice were used to construct a PSD mouse model using photothrombotic technique, and the swallowing function was evaluated by electromyography (EMG) recording. C-Fos-positive neurons and types of neurons in the NTS were detected by immunofluorescence. Optogenetics and chemical genetics were used to regulate the NTS, and the firing rate of neurons was recorded via multichannel recording. RESULTS: The results showed that most of the activated neurons in the NTS were excitatory neurons, and multichannel recording indicated that the activity levels of both pyramidal neurons and interneurons in the NTS were regulated by M1. This process was involved in the EA treatment. Furthermore, while chemogenetic inhibition of the NTS reduced the EMG signal associated with the swallowing response induced by activation of M1 in PSD mice, EA rescued this signal. CONCLUSION: Overall, the NTS was shown to participate in the regulation of PSD by EA at CV23 through M1.

15.
An Bras Dermatol ; 99(1): 27-33, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37657958

RESUMO

BACKGROUND: Primary cutaneous CD4+ small/medium-sized pleomorphic T-Cell lymphoproliferative disorder (PC-SMTLD) has been considered as a controversial dermatological disease that has been included in cutaneous T-cell lymphoma group, presenting most commonly as a solitary nodule and/or plaque with a specific and characteristic head and neck predilection. Due to the considerable overlap between PC-SMTLD and pseudolymphoma (PL), the differential diagnosis is often challenging. Methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, it has rarely been studied in cutaneous lymphomas. OBJECTIVES: The authors aimed to explore the role of differential 5-hmC immunostaining as a useful marker to distinguish PC-SMTLD from PL. METHODS: Retrospective case series study with immunohistochemical and immunofluorescence analysis of 5-hmC was performed in PL and PC-SMTLD. RESULTS: Significant decrease of 5-hmC nuclear staining was observed in PC-SMTLD when compared with PL (p < 0.0001). By semi-quantitative grade integration, there were statistical differences in the final 5-hmC scores in the two study groups. The IF co-staining of 5-hmC with CD4 revealed a decrease of 5-hmC in CD4+ lymphocytes of PC-SMTLD. STUDY LIMITATIONS: The small clinical sample size of the study. CONCLUSIONS: The immunorreactivity of 5-hmC in CD4+ lymphocytes was highly suggestive of a benign process as PL. Furthermore, the decrease of 5-hmC nuclear staining in PC-SMTLD indicated its lymphoproliferative status and helped to make the differential diagnosis with PL.


Assuntos
Linfoma Cutâneo de Células T , Pseudolinfoma , Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Linfócitos T CD4-Positivos/patologia , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , Pseudolinfoma/patologia
16.
Front Public Health ; 11: 1232551, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38094228

RESUMO

Purpose: This study investigated the influence of parenting and grandparenting caregiving styles on fundamental motor skills (FMS) of preschool children. Method: A total of 1,326 preschool children (698 boys, 628 girls) aged 4-6 years were recruited from the kindergartens of Jinhua City, China. Locomotor skills (LM), ball skills (BS), and total fundamental movement skills (TS) of children were assessed by the Test of Gross Motor Development-3rd edition (TGMD-3). Results: There were 978 children in parenting and 348 children in grandparenting caregiving styles. The LM, BS and TS scores of children were considerably (p < 0.001) increased with age (irrespective of sex or caregiving style). For the sex comparisons, BS scores of boys were significantly higher than girls (p < 0.001), while LM and TS scores were not different between boys and girls. For the caregiving style comparison, parenting is superior to grandparenting in developing of children's FMS. Parenting boys of 4-, 5-, and 6-years old showed better BS compared to age-matched parenting girls, whereas boys of 5-years old in grandparenting only showed better BS compared to same-age grandparenting girls (p < 0.05). Furthermore, parenting boys of 6-years reported higher LM (p < 0.01), BS (p < 0.001), and TS (p < 0.001) scores compared to grandparenting boys, but girls' FMS at all ages were not significantly different between the caregiving styles. Conclusion: Parenting caregiving style is positively associated with proper development of FMS among children. Girl children with poor FMS in grandparenting may need a special care or intervention programs to promote their FMS.


Assuntos
Destreza Motora , Poder Familiar , Masculino , Feminino , Pré-Escolar , Humanos , Fatores Sexuais , Escolaridade , Instituições Acadêmicas
17.
J Med Internet Res ; 25: e45225, 2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37862061

RESUMO

BACKGROUND: The global pandemics of severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 have caused unprecedented crises for public health. Coronaviruses are constantly evolving, and it is unknown which new coronavirus will emerge and when the next coronavirus will sweep across the world. Knowledge graphs are expected to help discover the pathogenicity and transmission mechanism of viruses. OBJECTIVE: The aim of this study was to discover potential targets and candidate drugs to repurpose for coronaviruses through a knowledge graph-based approach. METHODS: We propose a computational and evidence-based knowledge discovery approach to identify potential targets and candidate drugs for coronaviruses from biomedical literature and well-known knowledge bases. To organize the semantic triples extracted automatically from biomedical literature, a semantic conversion model was designed. The literature knowledge was associated and integrated with existing drug and gene knowledge through semantic mapping, and the coronavirus knowledge graph (CovKG) was constructed. We adopted both the knowledge graph embedding model and the semantic reasoning mechanism to discover unrecorded mechanisms of drug action as well as potential targets and drug candidates. Furthermore, we have provided evidence-based support with a scoring and backtracking mechanism. RESULTS: The constructed CovKG contains 17,369,620 triples, of which 641,195 were extracted from biomedical literature, covering 13,065 concept unique identifiers, 209 semantic types, and 97 semantic relations of the Unified Medical Language System. Through multi-source knowledge integration, 475 drugs and 262 targets were mapped to existing knowledge, and 41 new drug mechanisms of action were found by semantic reasoning, which were not recorded in the existing knowledge base. Among the knowledge graph embedding models, TransR outperformed others (mean reciprocal rank=0.2510, Hits@10=0.3505). A total of 33 potential targets and 18 drug candidates were identified for coronaviruses. Among them, 7 novel drugs (ie, quinine, nelfinavir, ivermectin, asunaprevir, tylophorine, Artemisia annua extract, and resveratrol) and 3 highly ranked targets (ie, angiotensin converting enzyme 2, transmembrane serine protease 2, and M protein) were further discussed. CONCLUSIONS: We showed the effectiveness of a knowledge graph-based approach in potential target discovery and drug repurposing for coronaviruses. Our approach can be extended to other viruses or diseases for biomedical knowledge discovery and relevant applications.


Assuntos
COVID-19 , Reposicionamento de Medicamentos , Humanos , Reconhecimento Automatizado de Padrão , Bases de Conhecimento , Unified Medical Language System
18.
Int Immunopharmacol ; 124(Pt B): 110992, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37806106

RESUMO

Sepsis begins with vascular endothelial barrier breakdown and causes widespread organ failure. Protease-activated receptor 1 (PAR1) is an important target for modulating vascular endothelial permeability; however, little research has been undertaken in sepsis, and its putative molecular mechanism remains unknown. The vascular endothelial permeability was examined by detecting FITC-dextran flux. F-actin was examined by immunofluorescence (IF). PAR1, ERM phosphorylation, and RhoA/ROCK signaling pathway expression in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) line were examined by IF and Western blot. To develop the sepsis model, cecal ligation and puncture (CLP) were conducted. The PAR1 inhibitor SCH79797 was utilized to inhibit PAR1 expression in vivo. Vascular permeability in main organs weres measured by Evans blue dye extravasation. The pathological changes in main organs were examined by HE staining. The expression of PAR1, ERM phosphorylation, and the RhoA/ROCK signaling pathway was examined using IF, immunohistochemical and WB in CLP mice. In vitro, in response to LPS stimulation of HUVECs, PAR1 mediated the phosphorylation of ERM, promoted F-actin rearrangement, and increased endothelial hyperpermeability, all of which were prevented by inhibiting PAR1 or RhoA. Additionally, inhibiting PAR1 expression reduced RhoA and ROCK expression. In vivo, we showed that inhibiting PAR1 expression will reduce ezrin/radixin/moesin (ERM) phosphorylation to relieve vascular endothelial barrier dysfunction and thereby ameliorate multiorgan dysfunction syndrome (MODS) in CLP-induced septic mice. This study revealed that PAR1-mediated phosphorylation of ERM induced endothelial barrier dysfunction, which in turn led to MODS in sepsis, and that the RhoA/ROCK signaling pathway underlay these effects.


Assuntos
Receptor PAR-1 , Sepse , Humanos , Camundongos , Animais , Receptor PAR-1/metabolismo , Actinas/metabolismo , Fosforilação , Lipopolissacarídeos/farmacologia , Transdução de Sinais , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Sepse/metabolismo , Quinases Associadas a rho/metabolismo , Permeabilidade Capilar
20.
Plants (Basel) ; 12(15)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37570984

RESUMO

Alfin-like (AL) transcription factors are a family of plant-specific genes with a PHD-finger-like structural domain at the C-terminus and a DUF3594 structural domain at the N-terminus that play important roles in plant development and stress response. In the present study, genome-wide identification and analysis were performed of the AL protein family in cultivated tomato (Solanum lycopersicum) and three wild relatives (S. pennellii, S. pimpinellifolium, and S. lycopersicoides) to evaluate their response to different abiotic stresses. A total of 39 ALs were identified and classified into four groups and based on phylogenetic tree and evolutionary analysis were shown to have formed prior to the differentiation of monocotyledons and dicots. Moreover, cis-acting element analysis revealed that various phytohormone response and abiotic stress response elements were highly existed in tomato. In addition, further analysis of the SlAL3 gene revealed that its expression was induced by drought and salt stresses and localized to the nucleus. In conclusion, our findings concerning AL genes provide useful information for further studies on their functions and regulatory mechanisms and provide theoretical references for studying AL gene response to abiotic stresses in plants.

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