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1.
J Hazard Mater ; 421: 126704, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34325292

RESUMO

Cadmium (Cd) is a toxic environmental pollutant and induces toxic effects to organism. Nevertheless, the mechanism of Cd-induced toxicity in swine remains obscure. To explore this, 10 healthy 6-week-old weaned swine were placed into two groups stochastically, the Cd group was treated with a commercial diet containing 20 mg/kg Cd for 40 days. The results of histopathological and ultrastructural observations showed typical necrosis features and inflammatory cell infiltration in Cd group. Excessive Cd suppressed T-AOC and SOD activities, increased MDA content and ROS levels. Cd diet elevated the expression of RIPK1, RIPK3, and MLKL to activate the RIPK3-dependent necroptosis pathway. Results of Th1 and Th2 cytokines indicated that the levels of IL-4, IL-6 and IL10 was increased, while the level of IFN-γ was decreased, illustrating Th1/Th2 immune imbalance leads to aggravate inflammatory responses. Cd activated the TNF-α/NF-κB pathway and induced inflammatory responses via increasing the expression of HO-1, IL-1ß, iNOS, COX2. Heat shock proteins were notably elevated in response to inflammatory reactions. And these effects were inhibited by necrostatin-1 (Nec-1) and N-acetyl-cysteine (NAC). Altogether, these data demonstrated that Cd induced necroptosis and inflammation to aggravate small intestine injury in swine by increasing the excessive accumulation of ROS and imbalanced Th1/Th2, respectively.


Assuntos
NF-kappa B , Necroptose , Animais , Cádmio/toxicidade , Inflamação/induzido quimicamente , Intestino Delgado/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Suínos , Fator de Necrose Tumoral alfa
2.
Chemosphere ; 287(Pt 3): 132302, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34563781

RESUMO

Sedum plumbizincicola is an herbaceous species tolerant of excessive cadmium accumulation in above-ground tissues. The implications of membrane proteins, especially integrative membrane proteins, in Cd detoxification of plants have received attention in recent years, but a comprehensive profiling of Cd-responsive membrane proteins from Cd hyperaccumulator plants is lacking. In this study, the membrane proteins of root, stem, and leaf tissues of S. plumbizincicola seedlings treated with Cd solution for 0, 1 or 4 days were analyzed by Tandem Mass Tag (TMT) labeling-based proteome quantification (Data are available via ProteomeXchange with identifier PXD025302). Total 3353 proteins with predicted transmembrane helices were identified and quantified in at least one tissue group. 1667 proteins were defined as DAPs (differentially abundant proteins) using fold change >1.5 with p-values <0.05. The number of DAPs involved in metabolism, transport protein, and signal transduction was significantly increased after exposure to Cd, suggesting that the synthesis and decomposition of organic compounds and the transport of ions were actively involved in the Cd tolerance process. The number of up-regulated transport proteins increased significantly from 1-day exposure to 4-day exposure, from 5 to 112, 16 to 42, 18 to 44, in root, stem, and leaf, respectively. Total 352 Cd-regulated transport proteins were identified, including ABC transporters, ion transport proteins, aquaporins, proton pumps, and organic transport proteins. Heterologous expression of SpABCB28, SpMTP5, SpNRAMP5, and SpHMA2 in yeast and subcellular localization showed the Cd-specific transport activity. The results will enhance our understanding of the molecular mechanism of Cd hypertolerance and hyperaccumulation in S. plumbizincicola and will be benefit for future genetic engineering in phytoremediation.


Assuntos
Sedum , Poluentes do Solo , Biodegradação Ambiental , Cádmio/análise , Proteínas de Membrana Transportadoras , Proteoma , Sedum/metabolismo , Poluentes do Solo/análise
3.
Food Chem ; 370: 131010, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34530347

RESUMO

Laminaria japonica is a familiar marine plant and is often used as food due to its abundant carbohydrates, vitamins and minerals. As one of the main types of active substances in L. japonica, polysaccharides are widely used in the food and chemical industries and in medicine and healthcare due to their health benefits, such as immunoregulatory, antioxidant, and antidiabetic effects. However, there has been no systematic summary of the isolation, structural characterization and bioactivities of L. japonica polysaccharides (LJPs). Therefore, the present review includes a survey of extraction and purification methods for these bioactive molecules, along with a dissertation on the structural characterization of the carbohydrate components. Moreover, an overview of the most recent results related to LJP biological activities is provided. This review provides a useful reference for further research, production, and application of LJPs in functional foods and therapeutic agents.


Assuntos
Laminaria , Antioxidantes , Hipoglicemiantes , Extratos Vegetais , Polissacarídeos
4.
Exp Ther Med ; 23(1): 13, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34815765

RESUMO

[This corrects the article DOI: 10.3892/etm.2018.5715.].

5.
J Ethnopharmacol ; 283: 114713, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34626776

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry leaves have been used as traditional hypoglycemic medicine-food plant for thousand years in China. According to traditional Chinese medicine theory, type 2 diabetes mellitus (T2DM) belongs to the category of XiaoKe. Presently, the research of mulberry leaf hypoglycemic and lipid-lowering direction is mature, but the curative effects of alkaloids, flavonoids, polysaccharides, and other bioactive ingredients and the related mechanism is still unclear. AIM OF THE STUDY: This paper aims to study the efficacy and mechanism of alkaloids, flavonoids, polysaccharides, and other bioactive components in mulberry leaves in the treatment of T2DM individually. MATERIALS AND METHODS: The determination of levels of fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (T-Cho), and pyruvate kinase (PK), hexokinase (HK), and alanine aminotransferase (ALT/GPT) of in plasma of diabetic mice. Urine metabolomics was analyzed by UPLC-QTOF/MS to evaluate differential metabolites from multiple metabolic pathways. The glucose uptake of HepG2 cells and 3T3-L1 cells. Expression of Caspase-3 and caspase-9, inflammatory injury and p38MAPK/NF-κB signaling pathway in GLUTag cells. RESULTS: Our study revealed alkaloids, flavonoids, and polysaccharides in mulberry leaf could increase the levels of PK, HK, and ALT/GPT, and decrease the levels of TG and T-Cho significantly, and regulate glucose, amino acid, and lipid metabolism. Furthermore, 1-deoxynojirimycin (DNJ) and isoquercitrin (QG) both could increase glucose uptake and promote differentiation of HepG2 cells, increase PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibit AGEs-induced injury and apoptosis in GLUTag cells, reduce the expression of proteins related to AGEs/RAGE and p38MAPK/NF-κB pathway. Notably, isoquercitrin exhibited more pronounced anti-diabetic efficacy. CONCLUSIONS: The alkaloids, flavonoids, and polysaccharides from mulberry leaf exhibited hypoglycemic activity through the regulation of glucose, amino acid, and lipid metabolism. 1-DNJ and QG increased glucose uptake and promoted differentiation of HepG2 cells, increased PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibited AGEs-induced injury and apoptosis in GLUTag cells via the AGEs/RAGE and p38 MAPK/NF-κB pathway.

6.
Mol Med Rep ; 25(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34812474

RESUMO

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that Figs. 2 and 4, featured on p. 4820 and 4821 respectively, contained apparently matching control ß­actin western blots. The authors have consulted their original data, and realized that the control western blot images were inadvertently selected incorrectly for Fig. 2. The corrected version of Fig. 2, showing the relevant ß­actin bands for Fig. 2, is shown on the next page. Note that the errors in Fig. 2 did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 17: 4817­4822, 2018; DOI: 10.3892/mmr.2018.8449].

7.
BMC Pulm Med ; 21(1): 379, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809635

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in premature infants, characterized by alveolar dysplasia and pulmonary microvascular remodeling. In the present study, we have investigated the functional roles of ubiquitin proteasome pathway (UPP) in BPD, and its relationship with endoplasmic reticulum stress (ERS) mediated type II alveolar epithelial cell (AECII) apoptosis. METHODS: A hyperoxia-induced BPD rat model was constructed and the pathologic changes of lung tissues were evaluated by hematoxylin-eosin staining. Cell apoptosis and protein expression were determined by TUNEL assay and Western blotting, respectively. Further reagent kit with specific fluorescent substrate was utilized to measure the activity of 20 s proteasome. Meanwhile, AECII were cultured in vitro and exposed to hyperoxia. AECII apoptosis were measured by flow cytometry. In contrast, MG132 treatment was induced to explore UPP during hyperoxia exposure on AECII apoptosis and ERS sensors expression. RESULTS: A significant increase in apoptosis and total ubiquitinated proteins expression were observed in BPD rats and AECII culture, and the change of UPP was associated with ERS. In order to confirm the role of UPP in AECII apoptosis of BPD, AECII cells were treated by MG132 with the concentration of 10 µmol/L under hyperoxia exposure. We found that the proteins expression of glucose-regulated protein 78 (GRP-78), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), as well as AECII apoptosis were increased following MG132 treatment. Furthermore, the relatively up-regulated in the levels of total ubiquitinated proteins expression and 20 s proteasome activity were correlated with increased ERS sensors expression. CONCLUSIONS: Our findings indicate that UPP may participate in the ERS-induced AECII apoptosis under hyperoxia condition.

8.
Neoplasma ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34779642

RESUMO

Pancreatic ductal adenocarcinoma is a complex gastrointestinal tumor with high metastatic potential and poor prognosis. Actin-binding protein Girdin is highly expressed in a variety of tumors and promotes tumor genesis and progression. However, the mechanisms underlying the involvement of Girdin in pancreatic cancer have not been clarified. In this study, we observed that the expression of Girdin was upregulated in pancreatic cancer cells. The siRNA-mediated gene knockdown experiments showed that reduced expression of Girdin in pancreatic cancer cells inhibited cell proliferation, migration, and invasion, while promoting cell apoptosis. Functional assays revealed that c-MYC overexpression in pancreatic cancer cells could significantly increase the cell proliferation ability and rates of cell migration and invasion, while decreasing the apoptosis rate. It has been shown that phosphorylation plays a role in the functional regulation of the c-MYC gene. Subsequently, we examined the expression level of c-MYC in cells with manipulated expression of Girdin and identified a positive correlation between Girdin expression and c-MYC expression. Moreover, we found that Girdin knockdown in c-MYC-overexpressing pancreatic cancer cells slowed cell growth, blocked the cell cycle progression, significantly promoted apoptosis, and markedly decreased the cell migration and invasion. This finding indicated that silencing Girdin could mitigate the effect of c-MYC on promoting proliferation and metastasis of pancreatic cancer. Overall, this study provided evidence that Girdin promoted pancreatic cancer development presumably by regulating the c-MYC overexpression.

9.
Heart Rhythm ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808346

RESUMO

BACKGROUND: The literature on laminopathy with ventricular phenotype is extensive. However, the pathogenicity of LMNA variations in atrial lesions still lacks research. OBJECTIVE: To characterize the atrial phenotype and possible mechanisms in a large Chinese family with heart-hand syndrome carrying LMNA missense variant in rod 2B domain (c.1003C>T p.R335W). METHODS: Clinical characteristics were collected based on the pedigree investigation. Comprehensive functional analyses, including molecular dynamic simulation, cellular, and animal functional assays, determined the pathogenicity in atrial myopathy. RESULTS: In the pedigree investigation, 6/13 of the mutation carriers showed heterogeneous cardiac phenotypes, and eight carriers also had brachydactyly. In silico molecular dynamics simulations predicted increased binding energy of R335W mutant lamin A. Atrial cardiomyocytes (HL-1, hiPSC-derived atrial cardiomyocytes) expressing R335W showed abnormal nuclear morphology, compromised DNA repair, and dysfunctional contraction. Adult zebrafish expressing mutant lamin A showed increased P wave duration in the electrocardiogram, decreased A peak velocity in echocardiography, and atrial lesions under the transmission electron microscope. CONCLUSION: The LMNA p.R335W mutation leads to a familial heart-hand syndrome characterized by an overlapping phenotype of prominent atrial lesions and brachydactyly. The unstable lamin dimerization and impaired DNA repair are possible mechanisms underlying cardiac phenotypes. Our findings consolidated the genetic role in the course of atrial arrhythmias and cardiac aging, which is helpful to the diagnosis and treatment of cardiac laminopathy.

10.
Thorac Cancer ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741403

RESUMO

BACKGROUND: Chemoresistance is a major barrier limiting the therapeutic efficacy of late stage non-small cell lung cancer (NSCLC). In this study, we sought to use two-dimensional titanium carbide (2D Ti2 C) to reverse cisplatin resistance in NSCLC. METHODS: We first achieved favorable properties as a potential anti-tumor agent. We then compared cell viability and cisplatin uptake in chemoresistant NSCLC cells before and after the use of 2D Ti2 C. Afterwards, we explored the effects of 2D Ti2 C on intracellular antioxidant reserves, followed by evaluating the subsequent changes in the expression of core drug resistance genes. Finally, we confirmed the tumor inhibitory effect and bio-safety of 2D Ti2 C in a drug-resistant lung cancer model in nude mice. RESULTS: Due to the properties of thin layer, large specific surface area, and abundant reactive groups on the surface, 2D Ti2 C can deplete the antioxidant reserve systems such as the glutathione redox buffer system, γ-glutamylcysteine synthetase (γ-GCS), glutathione peroxidase (GPx), glutathione-S-transferase-Pi (GST-π), and metallothionein (MT), thereby increasing the intracellular accumulation of cisplatin and decreasing the expression of drug resistance genes. CONCLUSIONS: 2D Ti2 C can reverse NSCLC chemoresistance both in vitro and in vivo, suggesting that it may potentially become a novel and effective means to treat chemoresistant NSCLC in the clinic.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34794961

RESUMO

OBJECTIVE: To identify factors that likely contribute to potentially inappropriate prescriptions (PIPs) among older adults in primary care settings, as well as barriers to medicines optimisation and recommended potential solutions. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Quantitative studies that analysed the factors associated with PIPs among older adults (≥65 years) in primary care settings, and qualitative studies that explored perceived barriers and potential solutions to medicines optimisation for this population. INFORMATION SOURCES: PubMed, EMBASE, Scopus, CINAHL, PsycINFO, Web of Science, CNKI and Wanfang. RESULTS: Of the 13 167 studies identified, 50 were included (14 qualitative, 34 cross-sectional and 2 cohort). Nearly all quantitative studies examined patient-related non-clinical factors (eg, age) and clinical factors (eg, number of medications) and nine studies examined prescriber-related factors (eg, physician age). A greater number of medications were identified as positively associated with PIPs in 25 quantitative studies, and a higher number of comorbidities, physical comorbidities and psychiatric comorbidities were identified as patient-related clinical risk factors for PIPs. However, other factors showed inconsistent associations with the PIPs. Barriers to medicines optimisation emerged within four analytical themes: prescriber related (eg, inadequate knowledge, concerns of adverse consequences, clinical inertia, lack of communication), patient related (eg, limited understanding, patient non-adherence, drug dependency), environment related (eg, lack of integrated care, insufficient investment, time constraints) and technology related (eg, complexity of implementation and inapplicable guidance). Recommended potential solutions were based on each theme of the barriers identified accordingly (eg, prescriber-related factors: incorporating training courses into continuing medical education). CONCLUSIONS: Older adults with more drugs prescribed and comorbidities may have a greater risk of receiving PIPs in the primary care setting, but it remains unclear whether other factors are related. Barriers to medicines optimisation among primary care older adults comprise multiple factors, and evidence-based and targeted interventions are needed to address these difficulties. PROSPERO REGISTRATION NUMBER: CRD42020216258.

12.
Front Physiol ; 12: 718068, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616306

RESUMO

Background: The influences of age and sex on properties of lumbar erector spinae have not been previously studied. Changes in the performance of lumbar erector spinae properties associated with age represent a valuable indicator of risk for lower-back-related disease. Objective: To investigate the lumbar erector spinae properties with regard to age and sex to provide a reference dataset. Methods: We measured muscle tone and stiffness of the lumbar erector spinae (at the L3-4 level) in healthy men and women (50 young people, aged 20-30 years; 50 middle-aged people, aged 40-50 years; and 50 elderly people, aged 65-75 years) using a MyotonPRO device. Results: In general, there are significant differences in muscle tone and stiffness among young, middle-aged, and elderly participants, and there were significant differences in muscle tone and stiffness between men and women, and there was no interaction between age and sex. The muscle tone and stiffness of the elderly participants were significantly higher than those of the middle-aged and young participants (P < 0.01), and the muscle tone and stiffness of the middle-aged participants were significantly higher than those of the young participants (P < 0.01). In addition, the muscle tone and stiffness of men participants were significantly higher than that of women participants (P < 0.01). Conclusion: Our results indicate that muscle tone and stiffness of the lumbar erector spinae increase with age. The muscle tone and stiffness of the lumbar erector spinae in men are significantly higher than in women. The present study highlights the importance of considering age and sex differences when assessing muscle characteristics of healthy people or patients.

13.
Int Orthop ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34647137

RESUMO

PURPOSE: To summarize the evolution of Ilizarov technology in China, highlight important milestones, introduce the atmosphere of the era concerning the first uses and development of this technology, and share Chinese modification and experience in this field. METHOD: A thorough interview with senior ASAMI members of China and literature search and physical books in libraries was undertaken to summarize the history of Ilizarov technology in China. RESULTS: The formal development of Ilizarov technology began when professor Ilizarov himself came to Beijing (1991) and gave a speech. In the following 31 years, his technology was rapidly developed through China, with many symposiums held and associations established including ASAMI China (2003) and ILLRS China (2015). Today, Ilizarov technology has become the main treatment of complex fractures, defects, nonunion, infections, deformities, and chronic ischemic ulcers of the limbs. In those years, Chinese scholars also developed some special treatment methods and made many modifications to Ilizarov external fixators. CONCLUSION: Ilizarov technology has developed in China for 31 years. It revolutionized the treatment of complex limb traumas, deformities, and diseases. In the treatment of millions of patients, Chinese scholars had many unique experiences and made modifications to this technology which is worthy to share with the world.

14.
Exp Ther Med ; 22(5): 1316, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630670

RESUMO

Osteoporosis is a common metabolic disease that has a high incidence in postmenopausal women. Studies have indicated that oxidative damage plays an important role in the development of postmenopausal osteoporosis. Metformin has been showed to have the ability to relieve excessive oxidation. The aim of the present was to determine the therapeutic effect and potential mechanism of metformin in postmenopausal osteoporosis. Oxidative damage was stimulated in vitro by the addition of H2O2 to MC3T3-E1 cells and a mouse menopausal model was also constructed. Cell viability and flow cytometry experiments were performed to determine the effects of H2O2 and metformin treatment on apoptosis. Mitochondrial membrane potential was tested by JC-1 assays. Western blotting was used to detect the expression of mitochondrial apoptosis markers and antioxidant enzymes. Small interfering RNA was used to knockdown sirtuin3 (SIRT3), which was verified at the mRNA and protein levels. Bilateral ovariectomy was used to prepare menopausal mice, which were analyzed using micro-computed tomography. The results indicated that metformin is able to repair mitochondrial damage and inhibit the apoptosis of osteoblasts induced by H2O2, and also reverse bone mass loss in ovariectomized mice. Western blotting results demonstrated the involvement of SIRT3 in the production of antioxidant enzymes that are essential in protecting against mitochondrial injury. In addition, experiments with SIRT3 knockdown indicated that metformin reverses H2O2-induced osteoblast apoptosis by upregulating the expression of SIRT3 via the PI3K/AKT pathway. The results of the present reveal the pathogenesis of oxidative damage and the therapeutic effect of metformin in postmenopausal osteoporosis. They also suggest that SIRT3 is a potential drug target in the treatment of osteoporosis, with metformin being a candidate drug for modification and/or clinical application.

15.
World J Gastroenterol ; 27(34): 5753-5763, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34629799

RESUMO

BACKGROUND: Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease (MAFLD). AIM: To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD), and nonalcoholic fatty liver disease fibrosis score (NFS) in patients with MAFLD. METHODS: Consecutive patients with histologically confirmed MAFLD were included. The discrimination ability of different non-invasive scores was compared. RESULTS: A total of 417 patients were included; 156 (37.4%) of them had advanced fibrosis (Metavir ≥ F3). The area under receiver operating characteristic curve of FIB-4, NFS, APRI, and BARD for predicting advanced fibrosis was 0.736, 0.724, 0.671, and 0.609, respectively. The area under receiver operating characteristic curve of FIB-4 and NFS was similar (P = 0.523), while the difference between FIB-4 and APRI (P = 0.001) and FIB-4 and BARD (P < 0.001) was statistically significant. The best thresholds of FIB-4, NFS, APRI, and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05, -2.1, 0.42, and 2. A subgroup analysis showed that FIB-4, APRI, and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD group. CONCLUSION: APRI and BARD scores do not perform well in MAFLD. The FIB-4 and NFS could be more useful, but a new threshold is needed. Novel non-invasive scoring systems for fibrosis are required for MAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Biópsia , Humanos , Cirrose Hepática/diagnóstico , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Contagem de Plaquetas , Valor Preditivo dos Testes
16.
J Biomed Res ; 35(5): 395-407, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34628405

RESUMO

Brugada syndrome (BrS) is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death. Considering that its heterogeneity in clinical manifestations may result from genetic background, the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) may help to reveal cell phenotype characteristics underlying different genetic variations. Here, to verify and compare the pathogenicity of mutations (SCN5A c.4213G>A andSCN1B c.590C>T) identified from two BrS patients, we generated two novel BrS iPS cell lines that carried missense mutations inSCN5A or SCN1B, compared their structures and electrophysiology, and evaluated the safety of quinidine in patient-specific iPSC-derived CMs. Compared to the control group, BrS-CMs showed a significant reduction in sodium current, prolonged action potential duration, and varying degrees of decreased Vmax, but no structural difference. After applying different concentrations of quinidine, drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration (ETPC). The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A orSCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.

17.
Sensors (Basel) ; 21(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34695971

RESUMO

Medium and small-scale high-clearance sprayers are widely applied in medium and small-scale farms. Owing to power and load limitations, it is difficult to manage the complex system for suppressing spray boom vibration. This study was conducted to design a spray boom-air suspension system suitable for medium and small-size high-clearance sprayers by combining spray boom vibration suppression and the characteristics of air spring charging/discharging. Thus, this study aims to address the non-homogeneous distribution of spray triggered by the spray boom vibrations in medium and small high-clearance sprayers. The effects of different elastic elements on the vibration suppression effect of the spray boom were compared. According to the bench test, the dynamic response results of the spray boom under transient and sinusoidal excitations indicate that air spring is more conducive to vibration suppression than coil spring. The results obtained from the field experiments indicate that under the low solid soil condition, the spray boom air suspension should match a small additional air chamber with a volume of approximately 0.6 L, and the damping coefficient of the damper should be approximately 1792 N·s/m. In the case of the high firm soil, the spray boom air suspension should match a large additional air chamber with a volume of approximately 3.6 L, while the damping coefficient of the damper should be set to approximately 1316 N·s/m. The soil with low moisture content and high firmness are unfavorable to the vibration suppression of the spray boom. This study provides a reference for enhancing the vibration suppression of the spray boom-air suspension and improving the spray uniformity of the sprayer.


Assuntos
Agricultura , Vibração , Solo , Suspensões
18.
Sensors (Basel) ; 21(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34696038

RESUMO

The extraction of wheat lodging is of great significance to post-disaster agricultural production management, disaster assessment and insurance subsidies. At present, the recognition of lodging wheat in the actual complex field environment still has low accuracy and poor real-time performance. To overcome this gap, first, four-channel fusion images, including RGB and DSM (digital surface model), as well as RGB and ExG (excess green), were constructed based on the RGB image acquired from unmanned aerial vehicle (UAV). Second, a Mobile U-Net model that combined a lightweight neural network with a depthwise separable convolution and U-Net model was proposed. Finally, three data sets (RGB, RGB + DSM and RGB + ExG) were used to train, verify, test and evaluate the proposed model. The results of the experiment showed that the overall accuracy of lodging recognition based on RGB + DSM reached 88.99%, which is 11.8% higher than that of original RGB and 6.2% higher than that of RGB + ExG. In addition, our proposed model was superior to typical deep learning frameworks in terms of model parameters, processing speed and segmentation accuracy. The optimized Mobile U-Net model reached 9.49 million parameters, which was 27.3% and 33.3% faster than the FCN and U-Net models, respectively. Furthermore, for RGB + DSM wheat lodging extraction, the overall accuracy of Mobile U-Net was improved by 24.3% and 15.3% compared with FCN and U-Net, respectively. Therefore, the Mobile U-Net model using RGB + DSM could extract wheat lodging with higher accuracy, fewer parameters and stronger robustness.


Assuntos
Redes Neurais de Computação , Triticum , Agricultura
19.
PLoS One ; 16(10): e0258797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34679093

RESUMO

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is one of the most common malignant tumors. However, the etiology and exact molecular mechanism of LIHC are still not fully understood, which makes it urgent for us to further study the molecular events behind. METHODS: In this study, differences in mRNA expression between LIHC samples and normal adjacent samples were found through analyzing the TCGA database, and key targets were sought. We analyzed 371 LIHC samples and 50 normal adjacent samples according to P <0.01 and logFC>2.5, a total of 1092 genes were identified differentially expressed, including 995 up-regulated genes and 97 down-regulated genes. We predicted the interactions of these differentially expressed mRNAs, and used Cyto-Hubba to locate the hub gene-dynein cytoplasmic 1 intermediate chain 1 (DYNC1I1). RESULTS: Survival analysis showed that DYNC1I1 was a prognostic factor for LIHC male patients. Functional enrichment indicated that DYNC1I1 and differentially expressed interacting proteins were involved in the cell cycle. CONCLUSION: In conclusion, this study discovers that DYNC1I1 can be used as a prognostic marker for LIHC male patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Biologia Computacional/métodos , Dineínas do Citoplasma/genética , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Masculino , Prognóstico , Caracteres Sexuais , Análise de Sobrevida
20.
Int Immunopharmacol ; 101(Pt A): 108261, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34688134

RESUMO

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation, synovial hyperplasia, cartilage degeneration, bone erosion, and pannus. Immunoglobulin D (IgD) plays an important role in autoimmune diseases although the content of it in vivo is low. Increased concentrations of anti-IgD autoantibodies have been detected in many RA patients. IgD-Fc-Ig fusion protein is constructed by connecting human IgD Fc domain and IgG1 Fc domain, which specifically block the IgD/ IgDR pathway and regulate the function of cells expressing IgDR to treat RA. The expression levels of Wnt5A and Frizzled 5 are higher in RA synovial tissue specimens. The complex of Wnt5A-Fzd5-LRP5/6-CTHRC1 promotes the expression of hypoxia inducible factor-1α by activating nuclear factor kappa-B (NF-κB), leading to high expression of VEGF and participating in angiogenesis. VEGF is the strongest angiogenic factor found so far. Here, we aimed to explore whether IgD participates in synovitis by binding to IgDR and regulating the activation of Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in fibroblast synovial cells (FLSs), whether IgD-Fc-Ig fusion protein inhibits VEGF production in FLS of CIA and explore mechanism. We found that IgDR is expressed on MH7A and FLS. IgD promotes VEGF expression by activating Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in MH7A and FLS. After activation of Fzd5 with Wnt5A, IgD-Fc-Ig reduced VEGF-A level in the culture supernatant of MH7A stimulation by IgD. The expressions of CTHRC1, Fzd5, p-P65 and VEGF in MH7A and FLSs were down-regulated after IgD-Fc-Ig treatment. IgD-Fc-Ig suppressed the combination of CTHRC1 and Fzd5 as well. By using the animal model, we demonstrated that IgD-Fc-Ig suppress ankle CTHRC1 and Fzd5 production resulted in inhibition of index of joint inflammation of CIA rats, which were consistent with vitro results. Conclusively, IgD-Fc-Ig inhibits IgD and Wnt5A-induced angiogenesis and joint inflammation by suppressing the combination of CTHRC1 and Fzd5. Our results show that IgD-Fc-Ig exerts its suppressive effect on IgD and Wnt5A by Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway.

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