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1.
J Pediatr ; 273: 114133, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38838850

RESUMO

OBJECTIVE: To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T magnetic resonance imaging scan between 39 and 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. RESULTS: A total of 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5%-53%) higher brain abnormality scores than those without HDP exposure (P = .02), primarily driven by increased white matter injury/abnormality scores (P = .01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (P = .02) contributed to brain abnormality scores (22% of the total effect). CONCLUSIONS: Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

2.
J Chem Phys ; 159(16)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37902609

RESUMO

Researching ultrafast dynamics and creating coherent light sources will both benefit significantly from the establishment of polarization control in high-order harmonic generation (HHG). By employing the time-dependent density functional theory method, we investigate HHG of carbonyl sulfide molecules using a combination of a linear polarized infrared (IR) laser and a weaker orthogonal Terahertz (THz) field. Our findings show that by adjusting the amplitude of the THz field, the movement scale of electrons in the THz direction can be tuned, thereby one can control the harmonic intensity in the IR laser direction. This method allows for the creation of near-circularly polarized attosecond pulses. Furthermore, the ellipticity of the attosecond pulse may be changed by modifying the carrier-envelope phase of the IR laser pulse.

3.
Sci Rep ; 13(1): 15273, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37714903

RESUMO

Growth in preterm infants in the neonatal intensive care unit (NICU) is associated with increased global and regional brain volumes at term, and increased postnatal linear growth is associated with higher language scores at age 2. It is unknown whether these relationships persist to school age or if an association between growth and cortical metrics exists. Using regression analyses, we investigated relationships between the growth of 42 children born extremely preterm (< 28 weeks gestation) from their NICU hospitalization, standardized neurodevelopmental/language assessments at 2 and 4-6 years, and multiple neuroimaging biomarkers obtained from T1-weighted images at 4-6 years. We found length at birth and 36 weeks post-menstrual age had positive associations with language scores at 2 years in multivariable linear regression. No growth metric correlated with 4-6 year assessments. Weight and head circumference at 36 weeks post-menstrual age positively correlated with total brain volume and negatively with global cortical thickness at 4-6 years of age. Head circumference relationships remained significant after adjusting for age, sex, and socioeconomic status. Right temporal cortical thickness was related to receptive language at 4-6 years in the multivariable model. Results suggest growth in the NICU may have lasting effects on brain development in extremely preterm children.


Assuntos
Lactente Extremamente Prematuro , Unidades de Terapia Intensiva Neonatal , Recém-Nascido , Criança , Lactente , Humanos , Pré-Escolar , Antropometria , Encéfalo/diagnóstico por imagem , Idioma
4.
Opt Express ; 31(19): 30171-30183, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710565

RESUMO

The spectral features of high-order harmonic spectra can provide rich information for probing the structure and dynamics of molecules in intense laser fields. We theoretically study the high harmonic spectrum with the laser polarization direction perpendicular to the N2O molecule and find a minimum structure in the plateau region of the harmonic spectrum. Through analyzing the time-dependent survival probability of different electronic orbitals and the time-dependent wave packet evolution, it is found that this minimum position is caused by the harmonic interference of HOMO a, HOMO-1, and HOMO-3 a orbitals. Moreover, this interference minimum is discovered over a wide frequency range of 0.087 a.u. to 0.093 a.u., as well as a range of driving laser intensities with peak amplitudes between 0.056 a.u. and 0.059 a.u.. This study sheds light on the multi-electron effects and ultrafast dynamics of inner-shell electrons in intense laser pulses, which are crucial for understanding and controlling chemical reactions in molecules.

5.
Clin Perinatol ; 50(3): 643-652, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536769

RESUMO

Multicomponent fortification is the standard of care to support short-term growth in preterm infants receiving human milk. There is no consensus regarding the optimal timing, method, or products used to fortify human milk. Both bovine milk-based and human milk-based human milk fortifiers are safe options, though increased fortification and enrichment may be needed to achieve adequate growth. Additional studies are needed to evaluate newer fortifier products and fortification strategies.


Assuntos
Enterocolite Necrosante , Leite Humano , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Alimentos Fortificados , Recém-Nascido de muito Baixo Peso
6.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2396-2405, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37282869

RESUMO

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.


Assuntos
Arsênio , Arsenicais , Produtos Biológicos , Medicamentos de Ervas Chinesas , Arsênio/toxicidade , Arsênio/análise , Arsenicais/análise , Sulfetos , Trióxido de Arsênio , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/toxicidade , Medicamentos de Ervas Chinesas/análise
7.
Zhongguo Zhong Yao Za Zhi ; 48(10): 2699-2712, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37282930

RESUMO

Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.


Assuntos
Medicina Tradicional Chinesa , Padrões de Referência , Controle de Qualidade , Fermentação
8.
J Clin Med ; 12(3)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36769597

RESUMO

Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the Web of Science, PubMed, Scopus, Ovid, Cochrane Library, and Embase databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78-0.85), 0.89 (95%CI: 0.85-0.91), and 0.92 (95%CI: 0.89-0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66-0.79)) and a high specificity (0.87 (95%CI: 0.81-0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66-0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66-0.87), 0.80 (95%CI: 0.72-0.87), and 0.86 (95%CI: 0.83-0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality.

9.
Res Sq ; 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36798338

RESUMO

Objective: To evaluate the impact of a standardized feeding protocol and donor breast milk (DBM) provision on clinical outcomes in moderate preterm infants (MPT, 29-33 6/7 weeks gestational age). Study Design: A protocol for MPT infants born > 1500 g was implemented clinically to standardize feeding advancements at 30 mL/kg/day. Infants < 33 weeks received DBM. We retrospectively identified 131 and 144 infants born before and after implementation. Clinical data including central venous line (CVL) placement, feeding tolerance, growth, and provision of maternal breast milk (MBM) were collected. Result: Number of CVLs, days to full enteral volume (FEV), and MBM provision was unchanged. There was a narrower range of days to FEV post-implementation. Growth metrics were similar between eras. Conclusion: Implementation of a feeding protocol for MPT infants is associated with more consistent time to FEV With monitoring and appropriate fortification, DBM use in this population is not associated with worse growth outcomes.

10.
Proc Natl Acad Sci U S A ; 119(46): e2212406119, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36346846

RESUMO

Defense against ultraviolet (UV) radiation exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV defense mechanisms remains largely unexplored. Herein, we used integrated approaches to analyze UV responses in the highest-elevation frog, Nanorana parkeri. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. We also reveal genes related to UV defense and a corresponding temporal expression pattern in N. parkeri. Genomic and metabolomic analysis along with large-scale transcriptomic profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. We also identified several microRNAs that play important regulatory roles, especially in decreasing the expression levels of cell cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Thus, both expression shifts and gene mutations contribute to UV adaptation in N. parkeri. Our work demonstrates a genetic framework for evolution of UV defense in a natural environment.


Assuntos
Anuros , Raios Ultravioleta , Animais , Anuros/genética , Pele , Perfilação da Expressão Gênica , Antioxidantes
11.
Natl Sci Rev ; 8(9): nwaa263, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34691726

RESUMO

The Himalaya are among the youngest and highest mountains in the world, but the exact timing of their uplift and origins of their biodiversity are still in debate. The Himalayan region is a relatively small area but with exceptional diversity and endemism. One common hypothesis to explain the rich montane diversity is uplift-driven diversification-that orogeny creates conditions favoring rapid in situ speciation of resident lineages. We test this hypothesis in the Himalayan region using amphibians and reptiles, two environmentally sensitive vertebrate groups. In addition, analysis of diversification of the herpetofauna provides an independent source of information to test competing geological hypotheses of Himalayan orogenesis. We conclude that the origins of the Himalayan herpetofauna date to the early Paleocene, but that diversification of most groups was concentrated in the Miocene. There was an increase in both rates and modes of diversification during the early to middle Miocene, together with regional interchange (dispersal) between the Himalaya and adjacent regions. Our analyses support a recently proposed stepwise geological model of Himalayan uplift beginning in the Paleocene, with a subsequent rapid increase of uplifting during the Miocene, finally giving rise to the intensification of the modern South Asian Monsoon.

12.
J Tradit Chin Med ; 41(4): 571-580, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34392650

RESUMO

OBJECTIVE: To investigate the protective effect and possible mechanism of sodium Danshensu (SDSS) against pressure injury caused by ischemia/reperfusion (I/R) injury. METHODS: Sprague-Dawley rats were randomly divided into five groups of eight rats each: control group, model group, 10 mg/kg SDSS-treated group, 20 mg/kg SDSS-treated group, and 40 mg/kg SDSS-treated group. We used two round ferrite magnetic plates of 15 mm diameter and 3 mm thickness to establish stage 2 pressure injury model rats. Each rat was subjected to five cycles of ischemia and reperfusion to induce pressure injury. One cycle consisted of 2 h of ischemia and 0.5 h of reperfusion, which meant that each cycle included 2 h of pressure and 0.5 h of pressure relief. The outline of the wound was delineated by butter paper and marker pen, and histopathological changes were observed by hematoxylin and eosin staining. In addition, the number of apoptotic cells and the activity of caspase-3 were assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling and caspase-3 assay kits, respectively. The expression of apoptosis-regulatory proteins and inflammatory mediators was investigated by enzyme-linked immunosorbent assay. RESULTS: Results showed that treatment with SDSS for 7 d after establishing the pressure injury model remarkably improved the healing rate of the wound. SDSS also inhibited the levels of tumor ne- crosis factor-α, myeloperoxidase, and intercellular cell adhesion molecule-1; decreased the number of apoptotic cells; increased the ratio of B-cell lymphoma-2 (Bcl-2) / Bcl-2-associated X (Bax); and regulated the expression and activity of caspase-3. CONCLUSION: Our results suggest that SDSS exhibits a treatment efficacy for pressure injury caused by I/R injury possibly by inhibiting apoptosis and inflammatory response.


Assuntos
Úlcera por Pressão , Traumatismo por Reperfusão , Sódio , Animais , Ratos , Apoptose , Isquemia , Lactatos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética
13.
Nutrients ; 13(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445027

RESUMO

Protein content is often inadequate in donor breast milk (DBM), resulting in poor growth. The use of protein-enriched target-pooled DBM (DBM+) has not been examined. We compared three cohorts of very low birth weight (VLBW) infants, born ≤ 1500 g: DBM cohort receiving > 1-week target-pooled DBM (20 kcal/oz), MBM cohort receiving ≤ 1-week DBM, and DBM+ cohort receiving > 1-week DBM+. Infants followed a standardized feeding regimen with additional fortification per clinical discretion. Growth velocities and z-scores were calculated for the first 4 weeks (n = 69 for DBM, 71 for MBM, 70 for DBM+) and at 36 weeks post-menstrual age (n = 58, 64, 59, respectively). In total, 60.8% MBM infants received fortification >24 kcal/oz in the first 30 days vs. 78.3% DBM and 77.1% DBM+. Adjusting for SGA, length velocity was greater with DBM+ than DBM in week 1. Average weight velocity and z-score change were improved with MBM compared to DBM and DBM+, but length z-score decreased similarly across all groups. Incidences of NEC and feeding intolerance were unchanged between eras. Thus, baseline protein enrichment appears safe in stable VLBW infants. Weight gain is greatest with MBM. Linear growth comparable to MBM is achievable with DBM+, though the overall length trajectory remains suboptimal.


Assuntos
Alimentação com Mamadeira , Extração de Leite , Desenvolvimento Infantil , Proteínas Alimentares/administração & dosagem , Alimentos Fortificados , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Leite Humano , Valor Nutritivo , Fatores Etários , Peso ao Nascer , Estatura , Proteínas Alimentares/efeitos adversos , Feminino , Alimentos Fortificados/efeitos adversos , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Bancos de Leite Humano , Fatores de Tempo , Aumento de Peso
14.
World J Gastrointest Oncol ; 13(5): 351-365, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34040698

RESUMO

Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma (HCC). Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis, predicting responses to specific therapies, evaluating prognosis before or after therapy, as well as serving as novel therapeutic targets. Detection and analysis of proteins, metabolites, circulating nucleic acids, circulating tumor cells, and extracellular vesicles in body fluids (e.g., blood and urine) and gut microbiota (e.g., in feces) have excellent capabilities to improve different aspects of management of HCC. Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis, treatment, and monitoring responses of HCC to conventional therapies, most of which may improve diagnosis and management of HCC in the future. This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.

15.
Medicine (Baltimore) ; 100(12): e25307, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761733

RESUMO

ABSTRACT: In 2020, the new type of coronal pneumonitis became a pandemic in the world, and has firstly been reported in Wuhan, China. Chest CT is a vital component in the diagnostic algorithm for patients with suspected or confirmed COVID-19 infection. Therefore, it is necessary to conduct automatic and accurate detection of COVID-19 by chest CT.The clinical classification of patients with COVID-19 pneumonia was predicted by Radiomics using chest CT.From the COVID-19 cases in our institution, 136 moderate patients and 83 severe patients were screened, and their clinical and laboratory data on admission were collected for statistical analysis. Initial CT Radiomics were modeled by automatic machine learning, and diagnostic performance was evaluated according to AUC, TPR, TNR, PPV and NPV of the subjects. At the same time, the initial CT main features of the two groups were analyzed semi-quantitatively, and the results were statistically analyzed.There was a statistical difference in age between the moderate group and the severe group. The model cohort showed TPR 96.9%, TNR 99.1%, PPV98.4%, NPV98.2%, and AUC 0.98. The test cohort showed TPR 94.4%, TNR100%, PPV100%, NPV96.2%, and AUC 0.97. There was statistical difference between the two groups with grade 1 score (P = .001), the AUC of grade 1 score, grade 2 score, grade 3 score and CT score were 0.619, 0.519, 0.478 and 0.548, respectively.Radiomics' Auto ML model was built by CT image of initial COVID -19 pneumonia, and it proved to be effectively used to predict the clinical classification of COVID-19 pneumonia. CT features have limited ability to predict the clinical typing of Covid-19 pneumonia.


Assuntos
COVID-19/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Tomografia Computadorizada por Raios X/métodos , Adulto , Fatores Etários , Idoso , COVID-19/patologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , SARS-CoV-2 , Índice de Gravidade de Doença
16.
Front Pharmacol ; 12: 821485, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35222014

RESUMO

Non-small cell lung cancer (NSCLC) is a worldwide disease with a high morbidity and mortality rate, which is most derived from its metastasis. Some studies show that the epithelial-mesenchymal transition (EMT) process promotes lung cancer cell migration and invasion, leading to NSCLC metastasis. Total flavonoid aglycones extract (TFAE) isolated from Scutellaria baicalensis was reported to inhibit tumor growth and induce apoptosis. In this study, we found that baicalein, wogonin, and oroxylin-A were the active compounds of TFAE. After reconstructing with these three compounds [baicalein (65.8%), wogonin (21.2%), and oroxylin-A (13.0%)], the reconstructed TFAE (reTFAE) inhibited the EMT process of A549 cells. Then, bioinformatic technology was employed to elucidate the potential pharmacodynamic mechanism network of reTFAE. We identified the relationship between reTFAE and PI3K/Akt signaling pathways, with TWIST1 as the key protein. LY294002, the inhibitor of the PI3K/Akt signaling pathway, and knock-down TWIST1 could significantly enhance the efficacy of reTFAE, with increasing expression of epithelial markers and decreasing expression of mesenchymal markers in A549 cells at the same time. Furthermore, stable isotope dimethyl-labeled proteomics technology was conducted to complement the follow-up mechanism that the EMT-inhibition process may be realized through the glycolysis pathway. In conclusion, we claim that TWIST1-targeted flavonoids could provide a new strategy to inhibit EMT progress for the treatment of NSCLC.

17.
Acta Pharmacol Sin ; 42(8): 1354-1367, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33122823

RESUMO

Group I metabotropic glutamate receptors (mGlu1 and mGlu5) are promising targets for multiple psychiatric and neurodegenerative disorders. Understanding the subtype selectivity of mGlu1 and mGlu5 allosteric sites is essential for the rational design of novel modulators with single- or dual-target mechanism of action. In this study, starting from the deposited mGlu1 and mGlu5 crystal structures, we utilized computational modeling approaches integrating docking, molecular dynamics simulation, and efficient post-trajectory analysis to reveal the subtype-selective mechanism of mGlu1 and mGlu5 to 10 diverse drug scaffolds representing known negative allosteric modulators (NAMs) in the literature. The results of modeling identified six pairs of non-conserved residues and four pairs of conserved ones as critical features to distinguish the selective NAMs binding to the corresponding receptors. In addition, nine pairs of residues are beneficial to the development of novel dual-target NAMs of group I metabotropic glutamate receptors. Furthermore, the binding modes of a reported dual-target NAM (VU0467558) in mGlu1 and mGlu5 were predicted to verify the identified residues that play key roles in the receptor selectivity and the dual-target binding. The results of this study can guide rational structure-based design of novel NAMs, and the approach can be generally applicable to characterize the features of selectivity for other G-protein-coupled receptors.


Assuntos
Regulação Alostérica/efeitos dos fármacos , Compostos Heterocíclicos/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Sítio Alostérico , Compostos Heterocíclicos/química , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Receptor de Glutamato Metabotrópico 5/antagonistas & inibidores , Receptor de Glutamato Metabotrópico 5/química , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/química , Termodinâmica
18.
Sci Rep ; 10(1): 18926, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144676

RESUMO

To explore the possibility of predicting the clinical types of Corona-Virus-Disease-2019 (COVID-19) pneumonia by analyzing the non-focus area of the lung in the first chest CT image of patients with COVID-19 by using automatic machine learning (Auto-ML). 136 moderate and 83 severe patients were selected from the patients with COVID-19 pneumonia. The clinical and laboratory data were collected for statistical analysis. The texture features of the Non-focus area of the first chest CT of patients with COVID-19 pneumonia were extracted, and then the classification model of the first chest CT of COVID-19 pneumonia was constructed by using these texture features based on the Auto-ML method of radiomics, The area under curve(AUC), true positive rate(TPR), true negative rate (TNR), positive predictive value(PPV) and negative predictive value (NPV) of the operating characteristic curve (ROC) were used to evaluate the accuracy of the first chest CT image classification model in patients with COVID-19 pneumonia. The TPR, TNR, PPV, NPV and AUC of the training cohort and test cohort of the moderate group and the control group, the severe group and the control group, the moderate group and the severe group were all greater than 95% and 0.95 respectively. The non-focus area of the first CT image of COVID-19 pneumonia has obvious difference in different clinical types. The AUTO-ML classification model of Radiomics based on this difference can be used to predict the clinical types of COVID-19 pneumonia.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Aprendizado de Máquina , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , COVID-19 , Infecções por Coronavirus/patologia , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia
19.
Hypertens Res ; 43(10): 1089-1098, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32541849

RESUMO

Cardiac remodeling is an important pathological process ultimately leading to heart failure. Ubiquitin carboxy-terminal hydrolase 1 (UCHL1) is a deubiquitinase that plays a critical role in neurodegenerative diseases and cancer. However, its role in cardiac remodeling in spontaneously hypertensive rats remains unclear. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were administered the UCHL1 inhibitor LDN-57444 (20 µg/kg/day) from 2 months of age for 4 months. Blood pressure, cardiac hypertrophy, fibrosis, inflammation, and oxidative stress were evaluated by the tail-cuff system, echocardiography, and histological analysis. Gene and protein expression levels were examined by real-time PCR and immunoblotting analysis. At 6 months of age, the expression of UCHL at the mRNA and protein levels was significantly upregulated in SHRs compared with WKYs. Moreover, systolic blood pressure, cardiac performance, left ventricular (LV) hypertrophy, fibrosis, inflammation, and superoxide production were significantly increased in SHRs compared with WKYs, and these effects were markedly attenuated by LDN-57444 after 4 months of administration. These beneficial actions were possibly associated with a reduction in blood pressure and inactivation of multiple signaling pathways, including AKT, ERK1/2, STAT3, calcineurin A, TGF-ß/Smad2/3, and NF-κB. In conclusion, the results indicate that UCHL1 is involved in hypertensive cardiac remodeling in SHRs, and targeting UCHL1 activity may be a novel potential therapeutic approach for the treatment of hypertensive heart diseases.


Assuntos
Cardiomegalia/prevenção & controle , Hipertensão/tratamento farmacológico , Indóis/uso terapêutico , Oximas/uso terapêutico , Ubiquitina Tiolesterase/antagonistas & inibidores , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/etiologia , Avaliação Pré-Clínica de Medicamentos , Hipertensão/complicações , Hipertensão/metabolismo , Indóis/farmacologia , Miocárdio/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Oximas/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais/efeitos dos fármacos , Ubiquitina Tiolesterase/metabolismo
20.
Toxins (Basel) ; 11(11)2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752154

RESUMO

Venom injected into the host plays vital roles in facilitating successful parasitization and development for parasitoid wasps, especially those devoid of polydnavirus, and the abundant venom proteins appear to be most likely involved in parasitization success. Previously, we found the four most abundant venom proteins, including 4-coumarate:CoA ligase-like 4 (4CL4-like), in the Tetrastichus brontispae (Hymenoptera: Eulophidae) venom apparatus. In this study, we cloned, expressed T. brontispae 4CL4-like (Tb4CL4-like) in Escherichia coli, and investigated its immunosuppressive properties. The deduced amino acid sequence for Tb4CL4-like shares high identity at conserved amino acids associated with the acyl-activating enzyme (AAE) consensus motif but shows only <40% identity with the members in the AAE superfamily. mRNA abundance analysis indicated that Tb4CL4-like was transcribed mainly in the venom apparatus. Recombinant Tb4CL4-like inhibited Octodonta nipae (Coleoptera: Chrysomelidae) pupal cellular encapsulation and spreading by targeting the hemocyte cytoskeleton and reduced the hemocyte-mediated phagocytosis of E. coli in vivo. Moreover, Tb4CL4-like exhibited greater affinity to palmitic acid and linolenic acid based on the molecular docking assay and is hypothesized to be involved in fatty acid metabolism. In conclusion, our results suggest that Tb4CL4-like may be an immunity-related AAE protein that is involved in the regulation of host immunity through fatty acid metabolism-derived signaling pathways.


Assuntos
Venenos de Artrópodes/enzimologia , Enzimas/genética , Himenópteros/metabolismo , Imunossupressores/farmacologia , Animais , Clonagem Molecular , Besouros/efeitos dos fármacos , Besouros/crescimento & desenvolvimento , Enzimas/isolamento & purificação , Enzimas/farmacologia , Perfilação da Expressão Gênica , Genes de Insetos , Interações Hospedeiro-Parasita , Fagocitose/efeitos dos fármacos
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