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1.
J Environ Manage ; 320: 115906, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36056497

RESUMO

Phosphorus (P) cycling by microbial activity is highly relevant in the eutrophication of lakes. In this context, the contents of organic (Po) and inorganic (Pi) phosphorus, the activity of acid (ACP) and alkaline (ALP) phosphomonoesterase (Pase), and the abundances of bacterial Pase genes (phoD, phoC, and phoX) were studied in sediments from Budi Lake, a eutrophic coastal brackish water lake in Chile. Our results showed spatiotemporal variations in P fractions, Pase activities, and Pase gene abundances. In general, our results showed higher contents of Pi (110-144 mg kg-1), Po (512-576 mg kg-1), and total P (647-721 mg kg-1) in sediments from the more anthropogenized sampling sites in summer compared with those values of Pi (86-127 mg kg-1), Po (363-491 mg kg-1) and total P (449-618 mg kg-1) in less anthropogenized sampling sites in winter. In concordance, sediments showed higher Pase activities (µg nitrophenyl phosphate g-1 h-1) in sediments from the more anthropogenized sampling sites (9.7-22.7 for ACP and 5.9 to 9.6 for ALP) compared with those observed in less anthropogenized sampling sites in winter (4.2-12.9 for ACP and 0.3 to 6.7 for ALP). Higher abundances (gene copy g-1 sediment) of phoC (8.5-19 × 108), phoD (9.2-47 × 106), and phoX (8.5-26 × 106) genes were also found in sediments from the more anthropogenized sampling sites in summer compared with those values of phoC (0.1-1.1 × 108), phoD (1.4-2.4 × 106) and phoX (0.7-1.2 × 106) genes in the less anthropogenized sites in winter. Our results also showed a positive correlation between P contents, Pase activities, and abundances of bacterial Pase genes, independent of seasonality. The present study provided information on the microbial activity involved in P cycling in sediments of Budi Lake, which may be used in further research as indicators for the monitoring of eutrophication of lakes.


Assuntos
Lagos , Poluentes Químicos da Água , Chile , China , Monitoramento Ambiental/métodos , Eutrofização , Sedimentos Geológicos , Monoéster Fosfórico Hidrolases , Fósforo/análise , Águas Salinas , Poluentes Químicos da Água/análise
2.
Cancer Sci ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056599

RESUMO

Cell division cycle associated 7 (CDCA7) is a copy number amplification gene that contributes to the metastasis and invasion of tumors, including esophageal squamous cell carcinoma (ESCC). This present study aimed at clarifying whether high expression of CDCA7 promotes the metastasis and invasion of ESCC cell lines and exploring the underlying mechanisms implicated in EMT of ESCC. The role of CDCA7 in the regulation of ESCC metastasis and invasion was evaluated using ESCC cell lines. Expression of EMT-related markers including E-cadherin, N-cadherin, Vimentin, Snail and Slug, TGF-ß signaling pathway including Smad2/3, p-Smad2/3, Smad4 and Smad7 were detected in CDCA7 knockdown and overexpressed cell lines. Dual-Luciferase reporter assay and rescue assay were used to explore the underlying mechanisms that CDCA7 contributes to the metastasis and invasion of ESCC. High CDCA7 expression significantly promoted the metastasis and invasion of ESCC cell lines both in vivo and in vitro. Additionally, the expression of CDCA7 positively correlated with the expression of N-cadherin, Vimentin, Snail, Slug, TGF-ß signaling pathway and negatively correlated with the expression of E-cadherin. Furthermore, CDCA7 transcriptionally regulated the expression of Smad4 and Smad7. Knockdown of CDCA7 inhibited the TGF-ß signaling pathway and thus inhibited EMT. Our data indicated that CDCA7 was heavily involved in EMT by regulating the expression of Smad4 and Smad7 in TGF-ß signaling pathway. CDCA7 might be a new therapeutic target in the suppression of metastasis and invasion of ESCC.

3.
Open Life Sci ; 17(1): 865-880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045721

RESUMO

Ophiopogonis Radix, also known as Maidong in Chinese, is largely produced in the Sichuan and Zhejiang provinces: "Chuan-maidong (CMD)" and "Zhe-maidong (ZMD)," respectively. This study aimed to distinguish and evaluate the quality of CMD and ZMD. In this study, the tubers of CMD and ZMD were investigated using UPLC-Q/TOF-MS, GC-MS, and LC-MS methods, respectively. Overall, steroidal saponins, homoisoflavonoids, amino acids, and nucleosides were quickly identified. Furthermore, multivariate statistical analysis revealed that CMD and ZMD could be separated. Moreover, CMD showed higher levels of 4-aminobutanoic acid, glycine, l-proline, monoethanolamine, and serine than ZMD. Besides, the levels of chlorogenic acid, traumatic acid, cytidine, cadaverine, pyridoxine 5-phosphate, glutinone, and pelargonidin 3-O-(6-O-malonyl-ß-d-glucoside) were remarkably higher in ZMD than in CMD. Furthermore, these different constituents were mainly associated with galactose metabolism; starch and sucrose metabolism; cysteine and methionine metabolism; valine, leucine, and isoleucine biosynthesis; and glycerophospholipid metabolism. In general, these results showed many differences between the bioactive chemical constituents of Ophiopogon japonicus from different production areas, where ZMD performed better in the quality assessment than CMD, and that UPLC-Q/TOF-MS, GC-MS, and LC-MS are effective methods to discriminate medicinal herbs from different production areas.

4.
Acta Neurol Scand ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36062837

RESUMO

BACKGROUND: Robust collateral circulation is strongly associated with good outcomes in acute ischemic stroke (AIS). AIMS: To determine whether collateral circulation detected by arterial spin labeling (ASL) magnetic resonance imaging could predict good clinical outcome in AIS patients with 90 days follow-up. MATERIALS AND METHODS: Total 58 AIS patients with anterior circulation stroke were recruited. Collateral circulation was defined as arterial transit artifact in ASL images. Modified Rankin Scale (mRS), the Barthel Index, and National Institutes of Health Stroke Scale (NIHSS) were employed to evaluate neurological function for the baseline and 90 days follow-up. The percent changes of these scores were also calculated, respectively. Finally, a support vector classifier model of machine learning and receiver operating characteristic curve were employed to estimate the power of ASL collaterals (ASLcs) predicting the clinical outcome. RESULTS: Patients with ASLcs represented higher rate of good outcome (83.30% vs. 31.25%, p < .001) and lower follow-up mRS scores (p < .001), when compared to patients without ASLcs. There were significant differences for percent changes of mRS scores and NIHSS scores between these two groups. Further, the presence of ASLcs could predict good clinical outcome (OR, 1.54; 95% CI, 1.10-2.16), even after controlling for baseline NIHSS scores. The SVC model incorporating baseline NIHSS scores and ASLcs had significant predictive effect (accuracy, 79.3%; AUC, 0.806) on clinical prognosis for AIS patients. DISCUSSION: We targeted on the non-invasive assessment of collateral circulation using ASL technique and found that patients with ASLcs were more likely to have a good clinical outcome after AIS. This finding is of guiding significance for treatment selection and prognostic prediction. CONCLUSIONS: Early ASLcs assessment provides a good powerful tool to predict clinical outcome for AIS patients with 90 days follow-up.

5.
Biomed Pharmacother ; 153: 113482, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076582

RESUMO

Mesenchymal stem cells (MSCs) have therapeutic value in many diseases. Mitochondria transfer can promote wound healing and can potentially be applied to the repair of damaged tissue, but the specific mechanisms and regulatory factors involved remain unclear. In this review, we discuss the mechanistic basis of mitochondria transfer and factors that restore mitochondrial function in injured somatic cells.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias
6.
J Clin Nurs ; 2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36088570

RESUMO

AIMS AND OBJECTIVES: To assess the effectiveness of educational interventions and the relative effect of intervention duration on secondary prevention health behaviours in adults with coronary heart disease. BACKGROUND: Patient education can reduce disease progression and improve outcomes. However, there is a lack of knowledge of its efficacy and the relative impact of education duration on health behaviour change in this population. DESIGN: A systematic review and meta-analysis. METHODS: Seven electronic databases and grey literature were searched from Inception to July 2021. The review followed the PRISMA guidelines. This meta-analysis was analysed in Comprehensive Meta-Analysis version 3 software. Outcomes considered were disease knowledge and health behavioural outcomes. Data were pooled together with random-effects models using the inverse-variance method. The effect of education duration (<3 vs. ≥3 months) was examined by meta-regressions. RESULTS: In summary, 73 studies were included with a total of participants (n = 24,985) aged mean of 60.5 ± 5.7 years and mostly male (72.5%). Patient education improved all behaviours including disease knowledge at <6 and 6-12 months follow-up, the likelihood of quitting smoking at <6, and 6-12 months, medication adherence at <6 and 6-12 months; physical activity and exercise participation at <6 and 6-12 months and healthy dietary behaviours, at <6 and 6-12 months. Furthermore, education programmes with a longer duration (≥3 months) improved disease knowledge and physical activity more than shorter programmes. CONCLUSION: Patient education for secondary prevention, in various delivery modes and intensities, improves multiple self-reported health behaviours in patients with coronary heart disease. RELEVANCE TO CLINICAL PRACTICE: This study assessed the effectiveness of secondary prevention education and demonstrated improvements in all outcomes in this population. Longer duration programmes were more effective in improving disease knowledge and physical activity in the long term. These findings can assist the cardiac programmes' design, particularly in ensuring sufficient intervention duration.

7.
Biomed Res Int ; 2022: 5481552, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119923

RESUMO

Chronic kidney disease (CKD) is identified as a widespread chronic progressive disease jeopardizing public health which characterized by gradually loss of renal function. However, there is no efficient therapy to prevail over this disease. Our study was attempting to reveal hirudin's regulation to renal fibrosis as well as the molecular mechanism. We built renal fibrosis models on both cell and animal levels, which were subsequently given with hirudin disposal; then, we performed the transwell assay to estimate the cells' migration and had our detection to relevant proteins with western blot and immunofluorescence. Finally, we commenced both the identification and the determination to the hirudin targeted proteins and its downstream signaling pathways with the methods of network pharmacology. And the results turned out that when it was compared with the model group, the group with hirudin addition came with the suppression in the migration of renal tubular epithelial cells NRK-52E and with a conspicuous decline in the expressions of fibronectin, N-cadherin, vimentin, TGF-ß, and snail. After that, we predicted that there were 17 hirudin target points mainly involving in the PI3K-AKT signaling pathway. Our outcomes of the animal level demonstrated that the conditions of interstitial fibrosis, severe tubular dilatation or atrophy, inflammatory cell infiltration, and massive accumulation of interstitial collagen in the model group were withdrawn after the addition of hirudin. In addition, p-PDGFRß, p-PI3K, and p-AKT protein expressions were significantly reduced, and the PI3K/AKT pathway was downregulated after hirudin treatment in the model group of NRK-52E cells and animals. Therefore, we had our conclusion that hirudin is capable of suppressing the PI3K-AKT signaling pathway as well as the EMT by decreasing PDGFRß phosphorylation.


Assuntos
Nefropatias , Proteínas Proto-Oncogênicas c-akt , Animais , Caderinas/metabolismo , Regulação para Baixo , Transição Epitelial-Mesenquimal , Fibronectinas/metabolismo , Fibrose , Hirudinas/farmacologia , Nefropatias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Vimentina/metabolismo
8.
Front Endocrinol (Lausanne) ; 13: 982953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120452

RESUMO

Many patients with congenital adrenal hyperplasia (CAH) refrain from seeking pregnancy, suffer from infertility or worry about pregnancy complications, mainly due to genitalia abnormalities, anovulation, unreceptive endometrium and metabolic disturbances. Despite those challenges, many live births have been reported. In this systematic review, we focused on the key to successful assisted reproduction strategies and the potential pregnancy complications. We did a systematic literature search of Pubmed, Medline and Scopus for articles reporting successful pregnancies in CAH other than 21-hydroxylase deficiency, and found 25 studies reporting 39 pregnancies covering deficiency in steroidogenic acute regulatory protein, 17α-hydroxylase/17,20-lyase, 11ß-hydroxylase, P450 oxidoreductase, cytochrome b5 and 3ß-hydroxysteroid dehydrogenase. We summarized various clinical manifestations and tailored reproduction strategy for each subtype. Furthermore, a meta-analysis was performed to evaluate the pregnancy complications of CAH patients. A total of 19 cross-sectional or cohort studies involving 1311 pregnancies of classic and non-classic CAH patients were included. Surprisingly, as high as 5.5% (95% CI 2.3%-9.7%) of pregnancies were electively aborted, and the risk was significantly higher in those studies with a larger proportion of classic CAH than those with only non-classical patients (8.43% (4.1%-13.81%) VS 3.75%(1.2%-7.49%)), which called for better family planning. Pooled incidence of miscarriage was 18.2% (13.4%-23.4%) with a relative risk (RR) of 1.86 (1.27-2.72) compared to control. Glucocorticoid treatment in non-classical CAH patients significantly lowered the miscarriage rate when compared to the untreated group (RR 0.25 (0.13-0.47)). CAH patients were also more susceptible to gestational diabetes mellitus, with a prevalence of 7.3% (2.4%-14.1%) and a RR 2.57 (1.29-5.12). However, risks of preeclampsia, preterm birth and small for gestational age were not significantly different. 67.8% (50.8%-86.9%) CAH patients underwent Cesarean delivery, 3.86 (1.66-8.97) times the risk of the control group. These results showed that fertility is possible for CAH patients but special care was necessary when planning, seeking and during pregnancy. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=342642, CRD42022342642.


Assuntos
Aborto Espontâneo , Hiperplasia Suprarrenal Congênita , Complicações na Gravidez , Nascimento Prematuro , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/terapia , Estudos Transversais , Citocromos b5 , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hidroxiesteroide Desidrogenases , Recém-Nascido , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Reprodução , Esteroide 17-alfa-Hidroxilase
9.
Emerg Med Int ; 2022: 2791743, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090543

RESUMO

Acetaminophen (APAP) overdose is one of the leading causes of acute liver damage. Given N-acetylcysteine (NAC) and melatonin (MLT) both have an attenuated value for APAP-induced liver toxification, where an optimized integrated treatment has not been well deciphered. Here, by giving a single dose of APAP (500 mg/kg) to wild-type male mice, combined with a single dose of 500 mg/kg NAC or 100 mg/kg MLT separately as the therapeutic method, this study aimed to investigate the effects of NAC and melatonin (MLT) alone or combined on acetaminophen (APAP)-induced liver injury. In this study, NAC and MLT both partially have an alleviated function in APAP-challenged liver injury. However, MLT's add-on role strengthens the hepatoprotective effect of NAC on APAP-induced liver damage and resolute the inflammatory infiltration. Meanwhile, the combination of two reagents attenuates the decreased glutathione (GSH) and activation of the p38/JNK pathway. The combination of MLT and NAC can further ameliorate APAP-induced liver injury, which provides a novel strategy for drug-induced liver injury (DILI).

10.
Radiology ; : 220329, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36066369

RESUMO

Background Although deep learning has brought revolutionary changes in health care, reliance on manually selected cross-sectional images and segmentation remain methodological barriers. Purpose To develop and validate an automated preoperative artificial intelligence (AI) algorithm for tumor and lymph node (LN) segmentation with CT imaging for prediction of LN metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Materials and Methods In this retrospective study, patients with surgically resected, pathologically confirmed PDAC underwent multidetector CT from January 2015 to April 2020. Three models were developed, including an AI model, a clinical model, and a radiomics model. CT-determined LN metastasis was diagnosed by radiologists. Multivariable logistic regression analysis was conducted to develop the clinical and radiomics models. The performance of the models was determined on the basis of their discrimination and clinical utility. Kaplan-Meier curves, the log-rank test, or Cox regression were used for survival analysis. Results Overall, 734 patients (mean age, 62 years ± 9 [SD]; 453 men) were evaluated. All patients were split into training (n = 545) and validation (n = 189) sets. Patients who had LN metastasis (LN-positive group) accounted for 340 of 734 (46%) patients. In the training set, the AI model showed the highest performance (area under the receiver operating characteristic curve [AUC], 0.91) in the prediction of LN metastasis, whereas the radiologists and the clinical and radiomics models had AUCs of 0.58, 0.76, and 0.71, respectively. In the validation set, the AI model showed the highest performance (AUC, 0.92) in the prediction of LN metastasis, whereas the radiologists and the clinical and radiomics models had AUCs of 0.65, 0.77, and 0.68, respectively (P < .001). AI model-predicted positive LN metastasis was associated with worse survival (hazard ratio, 1.46; 95% CI: 1.13, 1.89; P = .004). Conclusion An artificial intelligence model outperformed radiologists and clinical and radiomics models for prediction of lymph node metastasis at CT in patients with pancreatic ductal adenocarcinoma. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chu and Fishman in this issue.

11.
J Virol ; : e0093022, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069544

RESUMO

Duck Tembusu virus (DTMUV) is an emerging pathogenic flavivirus that mainly causes a decrease in egg production in infected waterfowl. Similar to other members of the Flaviviridae family, it can proliferate in most mammalian cells and may also pose a potential threat to nonavian animals. In previous studies, we found that DTMUV infection can upregulate suppressor of cytokine signaling 1 (SOCS1) to inhibit type I interferon (IFN) production and promote virus replication, but the specific mechanism is unclear. Furthermore, little is known about the regulatory role of ubiquitination during flavivirus infection. In this study, we found that activation of Toll-like receptor 3 (TLR3) signaling rather than type I IFN stimulation led to the upregulation of SOCS1 during DTMUV infection. Further studies revealed that JOSD1 stabilized SOCS1 expression by binding to the SH2 domain of SOCS1 and mediating its deubiquitination. In addition, JOSD1 also inhibited type I IFN production through SOCS1. Finally, SOCS1 acts as an E3 ubiquitin ligase that binds to IFN regulatory factor 7 (IRF7) through its SH2 domain and mediates K48-linked ubiquitination and proteasomal degradation of IRF7, ultimately inhibiting type I IFN production mediated by IRF7 and promoting viral proliferation. These results will enrich and deepen our understanding of the mechanism by which DTMUV antagonizes the host interferon system. IMPORTANCE DTMUV is a newly discovered flavivirus that seriously harms the poultry industry. In recent years, there have been numerous studies on the involvement of ubiquitination in the regulation of innate immunity. However, little is known about the involvement of ubiquitination in the regulation of flavivirus-induced type I IFN signaling. In this study, we found that SOCS1 was induced by TLR3 signaling during DTMUV infection. Furthermore, we found for the first time that duck SOCS1 protein was also modified by K48-linked polyubiquitination, whereas our previous study found that SOCS1 was upregulated during DTMUV infection. Further studies showed that JOSD1 stabilized SOCS1 expression by mediating the deubiquitination of SOCS1. While SOCS1 acts as a negative regulator of cytokines, we found that DTMUV utilized SOCS1 to mediate the ubiquitination and proteasomal degradation of IRF7 and ultimately inhibit type I IFN production, thereby promoting its proliferation.

12.
J Affect Disord ; 318: 456-464, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36058363

RESUMO

BACKGROUND: Various populations have experienced significant increases in depression and decreased quality of life (QOL) during the coronavirus disease 2019 (COVID-19) pandemic. This network analysis study was designed to elucidate interconnections between particular depressive symptoms and different aspects of QOL and identify the most clinically important symptoms in this network among adults in Wuhan China, the initial epicenter of the COVID-19 pandemic. METHODS: This cross-sectional, convenience-sampling study (N = 2459) was conducted between May 25 to June 18, 2020, after the lockdown policy had been lifted in Wuhan. Depressive symptoms and QOL were measured with the Patient Health Questionnaire-9 (PHQ-9) and first two items of the World Health Organization Quality of Life Questionnaire - brief version (WHOQOL-BREF), respectively. A network structure was constructed from the extended Bayesian Information Criterion (EBIC) model. Network centrality strength and bridge strength were evaluated along with the stability of the derived network model. RESULTS: Loss of energy (DEP-4) and Guilt feelings (DEP-6) were the two central symptoms with the highest strength as well as the two most prominent bridge symptoms connecting the clusters of depression and quality of life (QOL) in tandem with the two nodes from the QOL cluster. Network structure and bridge strengths remained stable after randomly dropping 75 % of the sample. CONCLUSION: Interventions targeting "Loss of energy" and "Guilt feelings" should be evaluated as strategies for reducing depressive symptoms and promoting improved QOL in COVID-19-affected populations.

13.
Int Immunopharmacol ; 112: 109195, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36070627

RESUMO

BACKGROUND: Renal interstitial fibrosis (RIF) is the final pathway for chronic kidney diseases (CKD) to end-stage renal disease (ESRD). Dapagliflozin, a selective inhibitor of the sodium glucose co-transporter 2, reduced the risk of renal events in non-diabetic CKD patients in the DAPA-CKD trial. However, the effect and mechanism of dapagliflozin on RIF are not very clear. Currently, we evaluate the effects of dapagliflozin on RIF and systematically explore its mechanism. METHODS AND RESULTS: Firstly, unilateral ureteral obstruction (UUO) mouse model was established to evaluate effects of dapagliflozin on RIF, and results demonstrated dapagliflozin improved renal function and RIF of UUO mice independent of blood glucose control. Subsequently, transcriptome analysis was performed to explore the potential mechanism of dapagliflozin against RIF, which exhibited the therapeutic effect of dapagliflozin on RIF may be achieved through multiple pathways regulation. Then we verified the potential mechanisms with molecular biology methods, and found that dapagliflozin treatment significantly alleviated inflammation, apoptosis, oxidative stress and mitochondrial injury in kidneys of UUO mice. Furthermore, network pharmacology analysis was used to investigate the potential targets of dapagliflozin against RIF. Moreover, we also applied molecular docking and molecular dynamics simulation to predict the specific binding sites and binding capacity of dapagliflozin and hub target. CONCLUSIONS: Dapagliflozin had therapeutic effect on RIF independent of blood glucose control, and the protective effects probably mediated by multiple pathways and targets regulation.

14.
Front Pharmacol ; 13: 961154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091808

RESUMO

Background: Due to the constant mutation of virus and the lack of specific therapeutic drugs, the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still poses a huge threat to the health of people, especially those with underlying diseases. Therefore, drug discovery against the SARS-CoV-2 remains of great significance. Methods: With the main protease of virus as the inhibitor target, 9,614 genistein derivatives were virtually screened by LeDock and AutoDock Vina, and the top 20 compounds with highest normalized scores were obtained. Molecular dynamics simulations were carried out for studying interactions between these 20 compounds and the target protein. The drug-like properties, activity, and ADMET of these compounds were also evaluated by DruLiTo software or online server. Results: Twenty compounds, including compound 11, were screened by normalized molecular docking, which could bind to the target through multiple non-bonding interactions. Molecular dynamics simulation results showed that compounds 2, 4, 5, 11, 13, 14, 17, and 18 had the best binding force with the target protein of SARS-CoV-2, and the absolute values of binding free energies all exceeded 50 kJ/mol. The drug-likeness properties indicated that a variety of compounds including compound 11 were worthy of further study. The results of bioactivity score prediction found that compounds 11 and 12 had high inhibitory activities against protease, which indicated that these two compounds had the potential to be further developed as COVID-19 inhibitors. Finally, compound 11 showed excellent predictive ADMET properties including high absorption and low toxicity. Conclusion: These in silico work results show that the preferred compound 11 (ZINC000111282222), which exhibited strong binding to SARS-CoV-2 main protease, acceptable drug-like properties, protease inhibitory activity and ADMET properties, has great promise for further research as a potential therapeutic agent against COVID-19.

15.
Am J Clin Nutr ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36095136

RESUMO

BACKGROUND: Diagnosing cancer cachexia relies extensively on the patient-reported historic weight, and failure to accurately recall this information can lead to severe underestimation of cancer cachexia. OBJECTIVES: The present study aimed to develop inexpensive tools to facilitate the identification of cancer cachexia in patients without weight loss information. METHODS: This multicenter cohort study included 12774 patients with cancer. Cachexia was retrospectively diagnosed using Fearon's framework. Baseline clinical features, excluding weight loss, were modeled to mimic a situation where the patient is unable to recall their weight history. Multiple machine learning (ML) models were trained using 75% of the study cohort to predict cancer cachexia, with the remaining 25% of the cohort used to assess model performance. RESULTS: The study enrolled 6730 males and 6044 females (median age = 57.5 years). Cachexia was diagnosed in 5261 (41.2%) patients and most diagnoses were made based on the weight loss criterion. A 15-variable logistic regression (LR) model mainly comprising cancer types, gastrointestinal symptoms, tumor stage and serum biochemistry indices was selected among the various ML models. The LR model showed good performance for predicting cachexia in the validation data (area under the curve = 0.763, 95% confidence interval=[0.747, 0.780]). The calibration curve of the model demonstrated good agreement between predictions and actual observations (accuracy = 0.714, Kappa = 0.396, sensitivity = 0.580, specificity = 0.808, positive predictive value = 0.679, negative predictive value = 0.733). Subgroup analyses showed that the model was feasible in patients with different cancer types. The model was deployed as an online calculator and a nomogram, and was exported as predictive model markup language to permit flexible, individualized risk calculation. CONCLUSIONS: We developed a ML model that can facilitate the identification of cancer cachexia in patients without weight loss information, which might improve decision-making and lead to the development of novel management strategies in cancer care.

16.
Shanghai Kou Qiang Yi Xue ; 31(2): 193-197, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-36110079

RESUMO

PURPOSE: To investigate the clinical efficacy of miniscrew in controlling the roller coaster effect in long-distance space closure with clear aligner. METHODS: Sixteen adult patients with bimaxillary protrusion were selected. All cases were treated with clear aligner and their four first premolars were extracted. G6 was designed in all cases. In the experimental group, four miniscrews were inserted at the beginning of treatment to control the teeth in three dimensions; while in the control group, the miniscrews were not applied until obvious roller coaster effect appeared. Paired t test was used to analyze the data with Graphpad Prism 6.0 software package. RESULTS: All the extraction space was closed successfully and the lateral profile was improved significantly. The torque of the upper incisor was under well control and no roller coaster effect happened in the experimental group; while in the control group, the lingual inclination of the upper incisors and open bite of the posterior teeth developed(P<0.05). After the miniscrews intrusion of the upper anterior teeth, the occlusion relationship improved significantly. CONCLUSIONS: Miniscrews effectively prevents and eliminates the roller coaster effect in the process of long-distance space closure with clear aligner.


Assuntos
Aparelhos Ortodônticos Removíveis , Técnicas de Movimentação Dentária , Adulto , Parafusos Ósseos , Humanos , Incisivo , Técnicas de Movimentação Dentária/métodos , Resultado do Tratamento
17.
Arch Microbiol ; 204(10): 631, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121479

RESUMO

Streptomyces bingchenggensis is the main industrial producer of milbemycins, which are a group of 16-membered macrocylic lactones with excellent insecticidal activities. In the past several decades, scientists have made great efforts to solve its low productivity. However, a lack of understanding of the regulatory network of milbemycin biosynthesis limited the development of high-producing strains using a regulatory rewiring strategy. SARPs (Streptomyces Antibiotic Regulatory Proteins) family regulators are widely distributed and play key roles in regulating antibiotics production in actinobacteria. In this paper, MilR3 (encoded by sbi_06842) has been screened out for significantly affecting milbemycin production from all the 19 putative SARP family regulators in S. bingchenggensis with the DNase-deactivated Cpf1-based integrative CRISPRi system. Interestingly, milR3 is about 7 Mb away from milbemycin biosynthetic gene cluster and adjacent to a putative type II PKS (the core minimal PKS encoding genes are sbi_06843, sbi_06844, sbi_06845 and sbi_06846) gene cluster, which was proved to be responsible for producing a yellow pigment. The quantitative real-time PCR analysis proved that MilR3 positively affected the transcription of specific genes within milbemycin BGC and those from the type II PKS gene cluster. Unlike previous "small" SARP family regulators that played pathway-specific roles, MilR3 was probably a unique SARP family regulator and played a pleotropic role. MilR3 was an upper level regulator in the MilR3-MilR regulatory cascade. This study first illustrated the co-regulatory role of this unique SARP regulator. This greatly enriches our understanding of SARPs and lay a solid foundation for milbemycin yield enhancement in the near future.

18.
Cell Prolif ; : e13331, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36124714

RESUMO

OBJECTIVES: Mutant C/EBPα p30 (mp30), the product of C/EBPα double mutations (DM), lacks transactivation domain 1 and has C-terminal loss-of-function mutation. Acute myeloid leukaemia (AML) patients harbouring C/EBPα DM could be classified as a distinct subgroup with favourable prognosis. However, the underlying mechanism remains elusive. MATERIALS AND METHODS: Autophagy regulated by mp30 was detected by western blot and immunofluorescence. Immune infiltration analysis and GSEA were performed to investigate autophagic and inflammatory status of AML patients from the GSE14468 cohort. Flow cytometry was applied to analyse T cell activation. RESULTS: Mp30 inhibited autophagy by suppressing nucleus translocation of NF-κB. Autophagy-associated secretion of IL-1ß was decreased in mp30-overexpressed AML cells. Bioinformatic analysis revealed that inflammatory status was attenuated, while CD8+ T cell infiltration was upregulated in C/EBPα DM AML patients. Consistently, the proportion of CD8+ CD69+ T cells in peripheral blood mononuclear cells (PBMCs) was upregulated after co-culture with mp30 AML cell conditional culture medium. Knock-out of IL-1ß in AML cells also enhanced CD8+ T cell activation. Accordingly, IL-1ß expression was significantly reduced in the bone marrow (BM) cells of C/EBPα DM AML patients compared to the wildtype, while the CD8+ CD69+ T cell proportion was specifically elevated. CONCLUSIONS: C/EBPα DM alleviates immunosuppression of CD8+ T cells by inhibiting the autophagy-associated secretion of IL-1ß, which elucidated that repression of autophagy-related inflammatory response in AML patients might achieve a favourable clinical benefit.

19.
Water Res ; 223: 119028, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063704

RESUMO

Precipitation can affect the residence time of nitrogen compounds, and temperature can influence nitrogen transformation in soil. Therefore, we hypothesized that climate factors can affect the emissions of N2O, an important greenhouse gas produced via nitrogen transformation, by influencing the migration and transformation of nonpoint source nitrogen in soil. To test this hypothesis and quantify the effect of climate factors on N2O emissions, the SWAT model and the modified SWAT-N2O coupler were used to study the effect of climate factors on the migration and transformation of nonpoint source nitrogen and N2O emissions in an agricultural watershed from 2009 to 2018. Temperature affected N2O emissions more significant than precipitation, and N2O emissions increased with temperature and reached a plateau when the average monthly temperature was 23.0 °C. The N2O emissions first increased rapidly with precipitation due to the increase in moisture. However, when the average monthly precipitation reached 78.8 mm, the N2O emissions began to decrease because the residence time of nitrogen compounds in soil were reduced due to fast removal via runoff, which inhibits N2O emissions. Under the context of climate change with three scenarios (RCP2.6, RCP4.5, RCP8.5), temperature would increase gradually while precipitation would not change significantly from 2021 to 2080, as a result, the changes would increase N2O emissions by 6.7%, 32.3%, and 70.7%, respectively. This study quantifies the feedback of N2O emissions to climate change in croplands, providing a scientific basis for climate change mitigation and agricultural management.


Assuntos
Gases de Efeito Estufa , Nitrogênio , Agricultura , Fertilizantes , Nitrogênio/análise , Compostos de Nitrogênio , Óxido Nitroso/análise , Solo
20.
Food Chem ; 401: 134053, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36096008

RESUMO

Constructing robust group-specific probes and non-competitive analysis methods for small molecules in the fields of food analysis is of great significance. In this study, three diarrhetic shellfish poisons (DSPs) with high safety risks to humans were taken as models of group targets, and a non-competitive and turn-on format colorimetric aptasensor was constructed for simultaneous and highly sensitive detection of the class of DSPs. A pair of anti-DSP split aptamers were generated with group-specific binding affinity to the three targets. The split aptamers were then fabricated with a hybridization chain reaction (HCR)-enhanced AuNPs nanozyme. The aptasensor realized linear detection range of 187.5-3000 pM, high sensitivity with a limit of detection (LOD) as low as 65.36 pM, good selectivity, as well as good accuracy when analyzing the DSPs in shellfish samples. This study provides good reference for developing robust probes and facile biosensors to detect multiple small molecules in food matrix.

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