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1.
Plant Physiol ; 194(2): 684-697, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37850874

RESUMO

The molecular mechanisms controlling organ size during plant development ultimately influence crop yield. However, a deep understanding of these mechanisms is still lacking. UBIQUITIN-SPECIFIC PROTEASE14 (UBP14), encoded by DA3, is an essential factor determining organ size in Arabidopsis (Arabidopsis thaliana). Here, we identified two suppressors of the da3-1 mutant phenotype, namely SUPPRESSOR OF da3-1 1 and 2 (SUD1 and SUD2), which encode the E3 ligases MOS4-ASSOCIATED COMPLEX 3A (MAC3A) and MAC3B, respectively. The mac3a-1 and mac3b-1 mutations partially suppressed the high ploidy level and organ size phenotypes observed in the da3-1 mutant. Biochemical analysis showed that MAC3A and MAC3B physically interacted with and ubiquitinated UBP14/DA3 to modulate its stability. We previously reported that UBP14/DA3 acts upstream of the B-type cyclin-dependent kinase CDKB1;1 and maintains its stability to inhibit endoreduplication and cell growth. In this work, MAC3A and MAC3B were found to promote the degradation of CDKB1;1 by ubiquitinating UBP14/DA3. Genetic analysis suggests that MAC3A and MAC3B act in a common pathway with UBP14/DA3 to control endoreduplication and organ size. Thus, our findings define a regulatory module, MAC3A/MAC3B-UBP14-CDKB1;1, that plays a critical role in determining organ size and endoreduplication in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ligases/metabolismo , Tamanho do Órgão , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
2.
Plant Cell ; 34(4): 1308-1325, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-34999895

RESUMO

Endoreduplication, a process in which DNA replication occurs in the absence of mitosis, is found in all eukaryotic kingdoms, especially plants, where it is assumed to be important for cell growth and cell fate maintenance. However, a comprehensive understanding of the mechanism regulating endoreduplication is still lacking. We previously reported that UBIQUITIN-SPECIFIC PROTEASE14 (UBP14), encoded by DA3, acts upstream of CYCLIN-DEPENDENT KINASE B1;1 (CDKB1;1) to influence endoreduplication and cell growth in Arabidopsis thaliana. The da3-1 mutant possesses large cotyledons with enlarged cells due to high ploidy levels. Here, we identified a suppressor of da3-1 (SUPPRESSOR OF da3-1 6; SUD6), encoding CYCLIN-DEPENDENT KINASE G2 (CDKG2), which promotes endoreduplication and cell growth. CDKG2/SUD6 physically associates with CDKB1;1 in vivo and in vitro. CDKB1;1 directly phosphorylates SUD6 and modulates its stability. Genetic analysis indicated that SUD6 acts downstream of DA3 and CDKB1;1 to control ploidy level and cell growth. Thus, our study establishes a regulatory cascade for UBP14/DA3-CDKB1;1-CDKG2/SUD6-mediated control of endoreduplication and cell growth in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Ciclo Celular/genética , Quinases Ciclina-Dependentes/genética , Endorreduplicação/genética , Ubiquitina/genética
3.
J Anat ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690607

RESUMO

The human rotator cuff consists of four muscles, each with a complex, multipennate architecture. Despite the functional and clinical importance, the architecture of the human rotator cuff has yet to be clearly described in humans in vivo. The purpose of this study was to investigate the intramuscular, intermuscular, and interindividual variations in architecture and moment arms of the human rotator cuff. Muscle volumes, fascicle lengths, physiological cross-sectional areas (PCSAs), pennation angles, and moment arms of all four rotator cuff muscles were measured from mDixon and diffusion tensor imaging (DTI) scans of the right shoulders of 20 young adults. In accordance with the most detailed dissections available to date, we found substantial intramuscular variation in fascicle length (coefficients of variation (CVs) ranged from 26% to 40%) and pennation angles (CVs ranged from 56% to 62%) in all rotator cuff muscles. We also found substantial intermuscular and interindividual variations in muscle volumes, but relatively consistent mean fascicle lengths, pennation angles, and moment arms (CVs for all ≤17%). Moreover, when expressed as a proportion of total rotator cuff muscle volume, the volumes of individual rotator cuff muscles were highly consistent between individuals and sexes (CVs ≤16%), suggesting that rotator cuff muscle volumes scale uniformly, at least in a younger population without musculoskeletal problems. Together, these data indicate limited interindividual and intermuscular variability in architecture, which may simplify scaling routines for musculoskeletal models. However, the substantial intramuscular variation in architecture questions the validity of previously reported mean architectural parameters to adequately describe rotator cuff function.

4.
Radiol Med ; 129(5): 702-711, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38520649

RESUMO

PURPOSE: We to systematically evaluate the diagnostic performance of MRI radiomics in detecting extracapsular extension (EPE) of prostate cancer (PCa). METHODS: A literature search of online databases of PubMed, EMBASE, Cochrane Library, Web of Science, and Google Scholar online scientific publication databases was performed to identify studies published up to July 2023. The summary estimates were pooled with the hierarchical summary receiver-operating characteristic (HSROC) model. This study was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, the quality of included studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2) and the radiomics quality score (RQS). Meta-regression and subgroup analyses were performed to explore the impact of varying clinical settings. RESULTS: A total of ten studies met the inclusion criteria. The pooled sensitivity and specificity were 0.77 (95% CI 0.68-0.84, I2 = 83.5%) and 0.75 (95% CI 0.67-0.82, I2 = 83.5%), respectively, with an area under the HSROC curve of 0.88 (95% CI 0.85-0.91). Study quality was not high while assessing with the RQS. Substantial heterogeneity was observed between studies; however, meta-regression analysis did not reveal any significant contributing factors. CONCLUSIONS: MRI radiomics demonstrated moderate sensitivity and specificity, offering similar diagnostic performance with previous risk stratifications and models that primarily based on radiologists' subjective experience. However, all studies included were retrospective, thus the performance of radiomics needs to validate in prospective, multicenter studies.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Próstata , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Humanos , Masculino , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Valor Preditivo dos Testes , Radiômica
5.
Plant Physiol ; 190(4): 2217-2228, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36063458

RESUMO

Endoreduplication plays an important role in cell growth and differentiation, but the mechanisms regulating endoreduplication are still elusive. We have previously reported that UBIQUITIN-SPECIFIC PROTEASE14 (UBP14) encoded by DA3 interacts with ULTRAVIOLETB INSENSITIVE4 (UVI4) to influence endoreduplication and cell growth in Arabidopsis (Arabidopsis thaliana). The da3-1 mutant possesses larger cotyledons and flowers with higher ploidy levels than the wild-type. Here, we identify the suppressor of da3-1 (SUPPRESSOR OF da3-1 3; SUD3), which encodes SNW/SKI-INTERACTING PROTEIN (SKIP). Biochemical studies demonstrate that SUD3 physically interacts with UBP14/DA3 and UVI4 in vivo and in vitro. Genetic analyses support that SUD3 acts in a common pathway with UBP14/DA3 and UVI4 to control endoreduplication. Our findings reveal an important genetic and molecular mechanism by which SKIP/SUD3 associates with UBP14/DA3 and UVI4 to modulate endoreduplication.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Endorreduplicação , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição/metabolismo , Ciclo Celular
6.
Environ Sci Technol ; 57(20): 7867-7874, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37159911

RESUMO

Oxidative decomposition of polystyrene (PS) by insects has been previously demonstrated, yet little is known about the oxidation mechanism and its effect on the metabolism of plastics within the insect gut. Here, we demonstrate the generation of reactive oxygen species (ROS) in the gut of superworms (Zophobas atratus larvae) under different feeding trails, which in turn induced the oxidative decomposition of ingested PS. The ROS were commonly generated in the larva gut, and PS consumption resulted in a significant increase of ROS with a maximum ·OH of 51.2 µmol/kg, which was five times higher than in the bran feeding group. Importantly, scavenging of ROS significantly decreased the oxidative depolymerization of PS, indicating a vital role of ROS in effective PS degradation in the gut of superworms. Further investigation suggested that the oxidative depolymerization of PS was caused by the combinatorial effect of ROS and extracellular oxidases of gut microbes. These results demonstrate that ROS were extensively produced within the intestinal microenvironment of insect larvae, which greatly favored the digestion of ingested bio-refractory polymers. This work provides new insights into the underlying biochemical mechanisms of plastic degradation in the gut.


Assuntos
Besouros , Microbioma Gastrointestinal , Animais , Larva/metabolismo , Poliestirenos , Espécies Reativas de Oxigênio/metabolismo , Biodegradação Ambiental , Besouros/metabolismo , Plásticos , Estresse Oxidativo
7.
Int J Mol Sci ; 24(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38068934

RESUMO

Cancer stem cells (CSCs) play a pivotal role in drug resistance and metastasis. Among the key players, Forkhead box O3a (FOXO3a) acts as a tumor suppressor. This study aimed to unravel the role of FOXO3a in mediating the inhibitory effect of metformin on cancer stemness derived from paclitaxel (PTX)-resistant non-small-cell lung cancer (NSCLC) cells. We showed that CSC-like features were acquired by the chronic induction of resistance to PTX, concurrently with inactivation of FOXO3a. In line with this, knockdown of FOXO3a in PTX-sensitive cells led to changes toward stemness, while overexpression of FOXO3a in PTX-resistant cells mitigated stemness in vitro and remarkably curbed the tumorigenesis of NSCLC/PTX cells in vivo. Furthermore, metformin suppressed the self-renewal ability of PTX-resistant cells, reduced the expression of stemness-related markers (c-MYC, Oct4, Nanog and Notch), and upregulated FOXO3a, events concomitant with the activation of AMP-activated protein kinase (AMPK). All these changes were recapitulated by silencing FOXO3a in PTX-sensitive cells. Intriguingly, the introduction of the AMPK dominant negative mutant offset the inhibitory effect of metformin on the stemness of PTX-resistant cells. In addition, FOXO3a levels were elevated by the treatment of PTX-resistant cells with MK2206 (an Akt inhibitor) and U0126 (a MEK inhibitor). Collectively, our findings indicate that metformin exerts its effect on FOXO3a through the activation of AMPK and the inhibition of protein kinase B (Akt) and MAPK/extracellular signal-regulated kinase (MEK), culminating in the suppression of stemness in paclitaxel-resistant NSCLC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metformina , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Linhagem Celular Tumoral , Quinases de Proteína Quinase Ativadas por Mitógeno , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos
8.
Mol Psychiatry ; 26(11): 6562-6577, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33963287

RESUMO

The establishment of neural circuits depends on precise neuronal positioning in the cortex, which occurs via a tightly coordinated process of neuronal differentiation, migration, and terminal localization. Deficits in this process have been implicated in several psychiatric disorders. Here, we show that the transcription factor Tcf4 controls neuronal positioning during brain development. Tcf4-deficient neurons become mispositioned in clusters when their migration to the cortical plate is complete. We reveal that Tcf4 regulates the expression of cell adhesion molecules to control neuronal positioning. Furthermore, through in vivo extracellular electrophysiology, we show that neuronal functions are disrupted after the loss of Tcf4. TCF4 mutations are strongly associated with schizophrenia and cause Pitt-Hopkins syndrome, which is characterized by severe intellectual disability. Thus, our results not only reveal the importance of neuronal positioning in brain development but also provide new insights into the potential mechanisms underlying neurological defects linked to TCF4 mutations.


Assuntos
Hiperventilação , Deficiência Intelectual , Adesão Celular , Fácies , Humanos , Hiperventilação/genética , Hiperventilação/metabolismo , Deficiência Intelectual/genética , Neurônios/metabolismo , Fator de Transcrição 4/genética , Fator de Transcrição 4/metabolismo
9.
FASEB J ; 34(8): 10443-10461, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32539222

RESUMO

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme involved in energy metabolism. Recently, GAPDH has been suggested to have extraglycolytic functions in DNA repair, but the underlying mechanism for the GAPDH response to DNA damage remains unclear. Here, we demonstrate that the tyrosine kinase Src is activated under DNA damage stress and phosphorylates GAPDH at Tyr41. This phosphorylation of GAPDH is essential for its nuclear translocation and DNA repair function. Blocking the nuclear import of GAPDH by suppressing Src signaling or through a GAPDH Tyr41 mutation impairs its response to DNA damage. Nuclear GAPDH is recruited to DNA lesions and associates with DNA polymerase ß (Pol ß) to function in DNA repair. Nuclear GAPDH promotes Pol ß polymerase activity and increases base excision repair (BER) efficiency. Furthermore, GAPDH knockdown dramatically decreases BER efficiency and sensitizes cells to DNA damaging agents. Importantly, the knockdown of GAPDH in colon cancer SW480 cells and xenograft models effectively enhances their sensitivity to the chemotherapeutic drug 5-FU. In summary, our findings provide mechanistic insight into the new function of GAPDH in DNA repair and suggest a potential therapeutic target in chemotherapy.


Assuntos
Núcleo Celular/genética , Núcleo Celular/metabolismo , Dano ao DNA/genética , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/genética , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Fosforilação/genética , Quinases da Família src/metabolismo , Transporte Ativo do Núcleo Celular/genética , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , DNA/genética , DNA Polimerase beta/genética , DNA Polimerase beta/metabolismo , Reparo do DNA/genética , Feminino , Células HEK293 , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mutação/genética , Transporte Proteico/genética , Transdução de Sinais/genética , Quinases da Família src/genética
10.
Cereb Cortex ; 30(5): 3102-3115, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31845732

RESUMO

The dentate gyrus (DG) of the hippocampal formation plays essential roles in learning and memory. Defective DG development is associated with neurological disorders. Here, we show that transcription factor 4 (Tcf4) is essential for DG development. Tcf4 expression is elevated in neural progenitors of the dentate neuroepithelium in the developing mouse brain. We demonstrate that conditional disruption of Tcf4 in the dentate neuroepithelium leads to abnormal neural progenitor migration guided by disorganized radial glial fibers, which further leads to hypoplasia in the DG. Moreover, we reveal that Wnt7b is a key downstream effector of Tcf4 in regulating neural progenitor migration. Behavioral analysis shows that disruption of integrity of the DG impairs the social memory highlighting the importance of proper development of the DG. These results reveal a critical role for Tcf4 in regulating DG development. As mutations in TCF4 cause Pitt-Hopkins syndrome (PTHS) characterized by severe intellectual disability, our data also potentially provide insights into the basis of neurological defects linked to TCF4 mutations.


Assuntos
Movimento Celular/fisiologia , Giro Denteado/crescimento & desenvolvimento , Giro Denteado/metabolismo , Células-Tronco Neurais/metabolismo , Fator de Transcrição 4/biossíntese , Animais , Giro Denteado/embriologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Gravidez , Fator de Transcrição 4/genética
11.
J Environ Manage ; 279: 111823, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33348187

RESUMO

Air pollution has been a major health concern worldwide, such that there is an urgent need for exposure assessments of human exposure to air pollutants. As children are more active and may experience more exposure events than adults, it is more challenging to conduct exposure assessments for children. To obtain a general understanding of the impact that children's activity, associated with their respiratory rate (IR), has on estimated exposure risks, we adopted a simple model to narrow down children's exposure behaviors to four categories, which integrated children's regular schedules and the indoor-outdoor ratio (rI/O) of air pollutants. Although outdoor play only occupies approximately 8.6% of the total weekly time, the results indicate that, in general, outdoor play contributes to over 50% of the total exposure to air pollutants when rI/O is less than 0.1, which is due to children's relatively large IR during high-intensity activities. When air pollutants mainly originate from indoor sources (i.e., rI/O=3.0), indoor sitting (28%) and sleeping (36%) account for the major portion of the total exposure due to the longer exposure duration while outdoor events, including playing, walking, and sitting, account for ~15% of the total exposure. In addition, we applied a ratio function (RM/C) to compare our simple model to a common basic model, revealing that our simulated results are consistent with the basic model, i.e., 0.94≤RM/C≤1.12, if the rI/O of air pollutants falls in the range between 0.5 and 1.5. The sensitivity analysis indicates that indoor or outdoor play has a larger impact on the output results than other activity-related variables because of the correspondingly largest IR. We also incorporated weather factors to adjust children's activity schedules for winter and non-winter days showing the change in the contributions of children's activities to total exposure. For example, the contribution differential of outdoor play to the total exposure between winter and non-winter days is ~8% for air pollutants with an rI/O value of 0.1. Although other factors, such as the activity intensity level and concentration of air pollutant in the microenvironment, must be refined in future studies, our simple model can be applied as a convenient approach to arrange children's activity schedules against possible air pollutant exposure.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Criança , Exercício Físico , Humanos , Estações do Ano , Fatores de Tempo
12.
Org Biomol Chem ; 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32459237

RESUMO

An interesting cascade reaction of N-(2-(4,5-dihydrooxazol-2-yl)phenyl)benzamide in the presence of an acid ion exchange resin is described. In this reaction, a range of substrates bearing various substituent groups are well compatible. This work provides a green and atom-economical alternative approach for the synthesis of quinazolin-4-ones in good yields.

13.
J Immunol ; 192(8): 3765-77, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24646745

RESUMO

Resolvin D1 (7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) (RvD1), generated from ω-3 fatty docosahexaenoic acids, is believed to exert anti-inflammatory properties including inhibition of neutrophil activation and regulating inflammatory cytokines. In this study, we sought to investigate the effect of RvD1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. In vivo, RvD1 was injected i.v. (5 µg/kg) 8 h after LPS (20 mg/kg) administration, which markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema. In addition, rat lung tissue protein was isolated after intervention and we found RvD1 improved epithelial sodium channel (ENaC) α, γ, Na,K-adenosine triphosphatase (ATPase) α1, ß1 subunit protein expression and Na,K-ATPase activity. In primary rat alveolar type II epithelial cells stimulated with LPS, RvD1 not only upregulated ENaC α, γ and Na,K-ATPase α1 subunits protein expression, but also increased Na+ currents and Na,K-ATPase activity. Finally, protein kinase A and cGMP were not responsible for RvD1's function because a protein kinase A inhibitor (H89) and cGMP inhibitor (Rp-cGMP) did not reduce RvD1's effects. However, the RvD1 receptor (formyl-peptide receptor type 2 [FPR2], also called ALX [the lipoxin A4 receptor]) inhibitor (BOC-2), cAMP inhibitor (Rp-cAMP), and PI3K inhibitor (LY294002) not only blocked RvD1's effects on the expression of ENaC α in vitro, but also inhibited the AFC in vivo. In summary, RvD1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/cAMP/PI3K signaling pathway.


Assuntos
Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Células Epiteliais Alveolares/metabolismo , AMP Cíclico/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Receptores de Lipoxinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Lesão Pulmonar Aguda/genética , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/imunologia , Animais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ativação Enzimática/efeitos dos fármacos , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Ratos , ATPase Trocadora de Sódio-Potássio/genética
14.
AAPS PharmSciTech ; 15(3): 560-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24570374

RESUMO

The objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively.


Assuntos
Portadores de Fármacos , Flavanonas/administração & dosagem , Temperatura Alta , Plastificantes/química , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , Pirrolidinas/química , Tecnologia Farmacêutica/métodos , Compostos de Vinila/química , Água/química , Administração Oral , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Química Farmacêutica , Cristalografia por Raios X , Cães , Estabilidade de Medicamentos , Flavanonas/sangue , Flavanonas/química , Flavanonas/farmacocinética , Masculino , Modelos Químicos , Transição de Fase , Difração de Pó , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Int J Nurs Sci ; 11(1): 106-112, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38352293

RESUMO

Objective: This study aimed to translate and evaluate the psychometric properties of the Perinatal Missed Care Survey in China. Methods: The Perinatal Missed Care Survey was translated according to the guidelines of the cross-cultural debugging scale recommended by the American Academy of Orthopaedic Surgeons Evidence-Based Medicine Committee, including forward translation, back translation, cultural adaption, and content validation, and its Chinese version was used in a cross-sectional study conducted from February to April in 2023. A total of 491 midwives from 14 different level hospitals in southwest China were recruited through a convenience sampling method. The discrimination ability of the items was tested through item analysis, and construct validity was assessed through exploratory factory and confirmatory factor analyses. The content validity index and Cronbach's α coefficients evaluated content validity and reliability, respectively. Results: The Chinese version's item-total correlation coefficients ranged from 0.641 to 0.866 in part A and from 0.644 to 0.819 in part B (P < 0.001). Parts A and B's scale-level content validity indexes were 0.95, and the item-level content validity indexes were from 0.86 to 1.00. The three common factors of part A (necessary care, basic care, and postnatal care) and part B (communication, labor resources, and material resources) were extracted, accounting for 70.186% and 71.984% of the total variance, respectively. Confirmatory factor analysis indicated that the good fit of the three-factor models was acceptable. The Cronbach's α coefficients were 0.968 (part A) and 0.940 (part B). Conclusion: The Chinese version of the Perinatal Missed Care Survey is a reliable and valid instrument for assessing nursing care missed by midwives during labor and birth and the reasons it was missed. Studies with large sample sizes are needed to verify the instrument's applicability in China.

16.
Comput Biol Med ; 157: 106712, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36907033

RESUMO

Multi-modal skin lesion diagnosis (MSLD) has achieved remarkable success by modern computer-aided diagnosis (CAD) technology based on deep convolutions. However, the information aggregation across modalities in MSLD remains challenging due to severity unaligned spatial resolution (e.g., dermoscopic image and clinical image) and heterogeneous data (e.g., dermoscopic image and patients' meta-data). Limited by the intrinsic local attention, most recent MSLD pipelines using pure convolutions struggle to capture representative features in shallow layers, thus the fusion across different modalities is usually done at the end of the pipelines, even at the last layer, leading to an insufficient information aggregation. To tackle the issue, we introduce a pure transformer-based method, which we refer to as "Throughout Fusion Transformer (TFormer)", for sufficient information integration in MSLD. Different from the existing approaches with convolutions, the proposed network leverages transformer as feature extraction backbone, bringing more representative shallow features. We then carefully design a stack of dual-branch hierarchical multi-modal transformer (HMT) blocks to fuse information across different image modalities in a stage-by-stage way. With the aggregated information of image modalities, a multi-modal transformer post-fusion (MTP) block is designed to integrate features across image and non-image data. Such a strategy that information of the image modalities is firstly fused then the heterogeneous ones enables us to better divide and conquer the two major challenges while ensuring inter-modality dynamics are effectively modeled. Experiments conducted on the public Derm7pt dataset validate the superiority of the proposed method. Our TFormer achieves an average accuracy of 77.99% and diagnostic accuracy of 80.03% , which outperforms other state-of-the-art methods. Ablation experiments also suggest the effectiveness of our designs. The codes can be publicly available from https://github.com/zylbuaa/TFormer.git.


Assuntos
Dermatopatias , Humanos , Diagnóstico por Computador , Processamento de Imagem Assistida por Computador , Dermatopatias/diagnóstico por imagem
17.
Food Chem ; 407: 135116, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36493480

RESUMO

As a popular vegetable, the unique and pleasant aroma is the key quality characteristic of Toona sinensis. To explore the sources and differences of aroma, the volatilomic profiling in the leaves and shoots of seven T. sinensis cultivars were investigated by chemometric analysis. The results indicated that aroma differences of each cultivar can be distinguished by W5S, W1S, W1W and W2S sensors during E-nose analysis. More than two thirds of all volatile organic compounds (VOCs) were derived from the leaves of most cultivars, except for Ximu toon. Notably, 2-mercapto-3,4-dimethyl-2,3-dihydrothiophene, 3,4-dimethyl thiophene, methyl thiirane, isocaryophyllene and hexanal were the major VOCs in both the leaves and shoots of T. sinensis. By constructing a weighted correlation network model, 5 modules and 11 hub VOCs were identified in the leaf samples of all cultivars. The data indicate that differential intracellular metabolic responses are responsible for the aroma formation of seven T. sinensis cultivars.


Assuntos
Odorantes , Compostos Orgânicos Voláteis , Odorantes/análise , Toona , Quimiometria , Compostos Orgânicos Voláteis/análise , Folhas de Planta/química
18.
Bioresour Technol ; 370: 128544, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36584721

RESUMO

The production of hydroxyl radicals (OH) has been documented during composting. However, the effect of OH on composting efficiency remains unclear. Here, iron mineral supplemented thermophilic composting (imTC) is proposed and demonstrated for enhancing OH production and accelerating the maturation of composting. The results indicated that the maximum OH production of imTC was 1922.74 µmol·kg-1, which increased by 1.39 times than that of ordinary thermophilic composting (oTC). Importantly, the increase of OH could greatly enhance organic matter degradation and humic substances formation during imTC, resulting in shorting the maturity time by 25 %. Enrichment of laccase-producing bacteria resulted in higher laccase activity (31.85 U·g-1) in imTC compared with oTC (23.82 U·g-1), which may have contributed to the higher level of humification in imTC treatment. This work, for the first time, proposes a feasible strategy for improving composting efficiency through the regulation of OH production during aerobic composting.


Assuntos
Compostagem , Solo , Espécies Reativas de Oxigênio , Esgotos , Ferro , Lacase , Substâncias Húmicas/análise , Minerais
19.
Comput Methods Programs Biomed ; 229: 107315, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36586177

RESUMO

BACKGROUND AND OBJECTIVE: Due to the complexity of skin lesion features, computer-aided diagnosis of skin diseases based on multi-modal images is considered a challenging task. Dermoscopic images and clinical images are commonly used to diagnose skin diseases in clinical scenarios, and the complementarity of their features promotes the research of multi-modality classification in the computer-aided diagnosis field. Most current methods focus on the fusion between modalities and ignore the complementary information within each of them, which leads to the loss of the intra-modality relation. Multi-modality models for integrating features both within single modalities and across multiple modalities are limited in the literature. Therefore, a multi-modality model based on dermoscopic and clinical images is proposed to address this issue. METHODS: We propose a Multi-scale Fully-shared Fusion Network (MFF-Net) that gathers features of dermoscopic images and clinical images for skin lesion classification. In MFF-Net, the multi-scale fusion structure combines deep and shallow features within individual modalities to reduce the loss of spatial information in high-level feature maps. Then Dermo-Clinical Block (DCB) integrates the feature maps from dermoscopic images and clinical images through channel-wise concatenation and using a fully-shared fusion strategy that explores complementary information at different stages. RESULTS: We validated our model on a four-class two-modal skin diseases dataset, and proved that the proposed multi-scale structure, the fusion module DCBs, and the fully-shared fusion strategy improve the performance of MFF-Net independently. Our method achieved the highest average accuracy of 72.9% on the 7-point checklist dataset, outperforming the state-of-the-art single-modality and multi-modality methods with an accuracy boost of 7.1% and 3.4%, respectively. CONCLUSIONS: The multi-scale fusion structure demonstrates the significance of intra-modality relations between clinical images and dermoscopic images. The proposed network combined with the multi-scale structure, DCBs, and the fully-shared fusion strategy, can effectively integrate the features of the skin lesions across the two modalities and achieved a promising accuracy among different skin diseases.


Assuntos
Dermatopatias , Humanos , Dermatopatias/diagnóstico por imagem , Pele/diagnóstico por imagem , Clorobenzenos , Diagnóstico por Computador
20.
J Diabetes Sci Technol ; 17(5): 1212-1225, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37162011

RESUMO

OBJECTIVE: Dietary self-management is one key component to achieve optimal glycemic control. Advances in mobile health (mHealth) technology have reduced the burden of diabetes self-management; however, limited evidence has been known regarding the status of the current body of research using mHealth technology for dietary management for adults with type 2 diabetes. METHODS: Literature searches were conducted electronically using PubMed, CINAHL (EBSCO), Web of Science Core Collection, PsycINFO (Ovid), EMBASE (Ovid), and Scopus. Keywords and subject headings covered dietary management, type 2 diabetes, and mHealth. Inclusion criteria included studies that applied mHealth for dietary self-management for adults with type 2 diabetes and were published in English as full articles. RESULTS: This review (N = 15 studies) revealed heterogeneity of the mHealth-based dietary self-management or interventions and reported results related to physiological, dietary behavioral, and psychosocial outcomes. Twelve studies applied smartphone apps with varied functions for dietary management or intervention, while three studies applied continuous glucose monitoring (CGM) to guide dietary changes. Among 15 reviewed studies, only three of them were two-arm randomized clinical trial (RCT) with larger sample and 12-month study duration and 12 of them were pilot testing. Nine of 12 pilot studies showed improved HbA1c; most of them resulted in varied dietary changes; and few of them showed improved diabetes distress and depression. CONCLUSION: Our review provided evidence that the application of mHealth technology for dietary intervention for adults with type 2 diabetes is still in pilot testing. The preliminary effects are inconclusive on physiological, dietary behavioral, and psychosocial outcomes.


Assuntos
Diabetes Mellitus Tipo 2 , Aplicativos Móveis , Autogestão , Telemedicina , Humanos , Adulto , Autogestão/métodos , Diabetes Mellitus Tipo 2/terapia , Telemedicina/métodos , Tecnologia , Ensaios Clínicos Controlados Aleatórios como Assunto
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