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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 279: 121411, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35653809

RESUMO

The quality evaluation of nature polysaccharides is a tough nut to crack because of its high Mw distributions and larger polarity property. It is well-known that infrared spectroscopy and multiple regression modeling have been used for quantitative examinations in multiple fields, but it has not been applied to the compositional analysis of polysaccharides. In this study, attenuated total reflectance-fourier transform infrared spectroscopy is used to simultaneously quantify aldoses, ketose and uronic acids in Atractylodes polysaccharides by a combination of multivariate regressions. After experience of different data processing pretreatments, the resulting spectrum contains maximum amount of information of monosaccharide contents in Atractylodes polysaccharides. In this case, different smoothing points, derivatives, SNV and MSC are used in the pre-modeling spectrum processing and VIP screening is used to reduce the number of variables to simplify the calculation of the model. All the most optimal prediction models have both good prediction ability (R2 ≥ 0.9 and RPD > 3) and no over fitting (RMSEP/RMSEC < 3). This strategy has opened a new possibility for the nondestructive determination of complex monosaccharide compositions of natural polysaccharides in a short detection time, low equipment requirement and high experimental safety.

2.
Front Pharmacol ; 13: 918771, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721111

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown origin that usually results in death from secondary respiratory failure within 2-5 years of diagnosis. Recent studies have identified key roles of cytokine and growth factor pathways in the pathogenesis of IPF. Although there have been numerous clinical trials of drugs investigating their efficacy in the treatment of IPF, only Pirfenidone and Nintedanib have been approved by the FDA. However, they have some major limitations, such as insufficient efficacy, undesired side effects and poor pharmacokinetic properties. To give more insights into the discovery of potential targets for the treatment of IPF, this review provides an overview of cytokines, growth factors and their signaling pathways in IPF, which have important implications for fully exploiting the therapeutic potential of targeting cytokine and growth factor pathways. Advances in the field of cytokine and growth factor pathways will help slow disease progression, prolong life, and improve the quality of life for IPF patients in the future.

3.
Microbiol Spectr ; : e0261921, 2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35652699

RESUMO

CLA (conjugated linoleic acid) has attracted substantial attention due to its physiological functions, including regulating immunity, reducing obesity, and contributing to cancer suppression. In Lactiplantibacillus plantarum, CLA oleate hydratase (CLA-HY), CLA short-chain dehydrogenase (CLA-DH), and CLA acetoacetate decarboxylase (CLA-DC) catalyze the biotransformation of linoleic acid (LA) to CLA. However, the underlying transcriptional regulation mechanism of this pathway remains largely unknown. In this study, the potential transcriptional regulators that might bind to the cla promoter of L. plantarum AR195 were investigated by DNA pulldown. Interestingly, ArgR2, the transcriptional regulator of arginine metabolism, was identified as a potential regulator involved in the regulation of CLA biotransformation. Electrophoretic mobility shift assay (EMSA) and molecular interaction results demonstrated the specific binding of ArgR2 to the regulatory region of the cla operon. The knockout of argR2 led to the downregulation of cla-dh and cla-dc by 91% and 34%, respectively, resulting in a decline in the CLA yield by 14%. A segmental EMSA revealed that ArgR2 bound to three distinct sites in the cla regulatory region, and these binding sites were highly conserved and rich in AT. The regulatory mechanism of ArgR2 on CLA biosynthesis further expanded our knowledge of the regulatory mechanism of CLA biosynthesis in L. plantarum and laid the theoretical foundation for the production and application of CLA. IMPORTANCE CLA (conjugated linoleic acid) has received extensive attention owing to its important physiological functions. CLA from natural sources is far from meeting people's demands. Lactic acid bacteria can efficiently synthesize cis-9,trans-11-CLA and trans-10,cis-12-CLA, which possess physiological activities. However, little is known about the regulatory mechanism. In this study, we identified that the biosynthesis of CLA in L. plantarum AR195 was transcriptionally regulated by the arginine biosynthesis regulatory protein ArgR2. The regulation mechanism of ArgR2 on CLA biosynthesis lays a theoretical foundation for the regulation of CLA synthesis and industrial production.

4.
Biochem Biophys Res Commun ; 618: 127-132, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35717907

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has been previously shown to be associated with diabetes mellitus (DM) which is one of the most decisive risk factors for the faster progression of NAFLD to nonalcoholic steatohepatitis (NASH), fibrosis or advanced cirrhosis. However, the critical molecular pathway involved in the development of diabetic-induced liver injury is unclear. By the proteomic study of liver from high-fat diet (HFD)/streptozotocin(STZ)-induced diabetic mice, we revealed that the upregulation of S100A9 was involved in the development of NAFLD with DM. Moreover, we found that S100A9 silencing decreased proinflammatory response and inhibited the TLR4-NF-κB signaling in in-vitro study. Our findings provide new perspectives into the pivotal role of S100A9 for development of diabetic NAFLD and revealed that S100A9 is a critical molecule that links liver injury to inflammation of NAFLD with DM.

5.
Nanomaterials (Basel) ; 12(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35683667

RESUMO

Nanofiber membrane has high biological protection function because of its good waterproof and moisture permeability properties. However, this membrane usually lacks active antimicrobial properties, limiting the application in reusable bioprotective textiles. Herein, waterborne polyurethane-capped Ag nanoparticles (AgNPs) were synthesized by reducing silver nitrate in water by sodium borohydride in the presence of polyurethane. AgNP-embedded thermoplastic urethane (TPU) nanofiber membrane was prepared by electrospinning a mixed solution of AgNPs and TPU. As-prepared membranes with Ag content of 50-300 mg·kg-1 have an average diameter of 0.75, 0.64, and 0.63 µm and good fiber uniformity. The doping of AgNP-embedded nanomembrane showed increased breaking force probably because of the induced crystallization effect. Test results showed that as-prepared TPU nanofiber membrane with silver content as low as 100 mg·kg-1 showed good washing resistance. The antibacterial rates of E. coli and S. aureus remained 99.99% with 50 times of soaping or chlorine washing. The corresponding waterproof and moisture permeability properties of nanofiber membrane with a thickness of 0.1 mm remained nearly unchanged, i.e., moisture permeability of around 2600 g·m-2 per 24 h and the hydrostatic pressure resistance of around 400 Pa after 50 times of soaping or chlorine washing.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35695720

RESUMO

PURPOSE: Paliperidone is an atypical antipsychotic as effective as other atypical antipsychotics for schizophrenia. However, few studies have explored the efficacy of paliperidone for treatment-resistant schizophrenia. This study aimed to compare the efficacy and safety of paliperidone extended release (ER) versus olanzapine in schizophrenia patients with either poor treatment response or intolerable adverse effects due to standardized antipsychotic therapy. METHODS: This 12-week randomized, double-blind, multicenter study compared the treatment efficacy on psychotic symptoms, cognitive functions, and tolerance between paliperidone ER (6-15 mg/d, n = 45) and olanzapine (10-30 mg/d, n = 41) in treatment-resistant or treatment-intolerant patients with schizophrenia. The severity of psychotic symptoms was evaluated by the Positive and Negative Syndrome Scale and the Clinical Global Impression Severity of Illness Scale. The cognitive functions were assessed by the MATRICS Consensus Cognitive Battery. In addition, the metabolic impacts were evaluated by weight gain and waist circumference. RESULTS: Patients with either paliperidone ER or olanzapine treatment showed apparent improvement in psychotic symptoms, without significant intergroup difference. Twelve-week paliperidone ER or olanzapine treatment did not improve the cognitive functions. Both paliperidone ER and olanzapine treatment caused significant increase in weight and waist circumference, and olanzapine had a greater impact on waist circumference than paliperidone ER. In addition, both drugs were well tolerated. CONCLUSIONS: Paliperidone ER could be a safe alternative for treatment-resistant schizophrenia.

7.
Transl Cancer Res ; 11(5): 1005-1016, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35706801

RESUMO

Background: Bladder cancer (BC) is the tenth most common cancer in the world. Serum microRNA (miRNA) profiles previously have been reported as non-invasive biomarkers in cancer screening. The non-invasive and reliable diagnostic biomarkers are urgently needed for detecting BC, while cystoscopy is invasive. Our study aimed to identify candidate miRNAs in serum as potential diagnostic biomarkers for BC detection. Methods: This study was including the screening stage, training stage, and validation stage with 137 BC patients and 127 healthy controls (HCs). We identified the expression of 28 serum miRNAs from 5 BC pools and 3 HC pools in the initial screening stage. The other 112 BC patients and 112 HCs were randomly divided into training stage with 30 BC patients and 30 HCs and validation stages with 82 BC patients and 82 HCs. These HCs matched BC patients based on age and gender with P value >0.05. Identified dysregulated miRNAs were further confirmed in the training stage, and validation stages by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The diagnostic value of miRNAs was assessed by receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). Target genes of 3 candidate miRNAs were predicted by bioinformatic analysis. Results: Five miRNAs (miR-106a-5p, miR-145-5p, miR-132-3p, miR-7-5p and miR-148b-3p) in serum were obviously dysregulated in BC patients compared to HCs. The ability to diagnose BC of 3 candidate miRNAs was estimated by AUC, with miR-132-3p (AUC =0.781; sensitivity =68.29%, specificity =81.71%), miR-7-5p (AUC =0.778; sensitivity =59.76%, specificity =84.15%) and miR-148b-3p (AUC =0.837; sensitivity =81.71%, specificity =71.95%). Combined application of these candidate miRNAs with parallel test could improve the diagnostic value (AUC =0.922; sensitivity =90.24%, specificity =81.71%). BNC2, GAS7, and NTRK2, considered as target genes of the three-miRNA panel, may play an important role in the process of BC development. Conclusions: A three-miRNA panel in serum was identified for BC diagnosis in our study, which HCs were used for differential diagnosis. The three-miRNA panel (miR-132-3p, miR-7-5p, and miR-148b-3p) might be performed as a non-invasive and convenient diagnostic tool for BC screening and diagnosis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35696471

RESUMO

Segmentation of retinal vessels on fundus images plays a critical role in the diagnosis of micro-vascular and ophthalmological diseases. Although being extensively studied, this task remains challenging due to many factors including the highly variable vessel width and poor vessel-background contrast. In this paper, we propose a multiscale feature interaction network (MFI-Net) for retinal vessel segmentation, which is a U-shaped convolutional neural network equipped with the pyramid squeeze-and-excitation (PSE) module, coarse-to-fine (C2F) module, deep supervision, and feature fusion. We extend the SE operator to multiscale features, resulting in the PSE module, which uses the channel attention learned at multiple scales to enhance multiscale features and enables the network to handle the vessels with variable width. We further design the C2F module to generate and re-process the residual feature maps, aiming to preserve more vessel details during the decoding process. The proposed MFI-Net has been evaluated against several public models on the DRIVE, STARE, CHASE_DB1, and HRF datasets. Our results suggest that both PSE and C2F modules are effective in improving the accuracy of MFI-Net, and also indicate that our model has superior segmentation performance and generalization ability over existing models on four public datasets.

9.
J Pharm Biomed Anal ; 218: 114837, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-35659657

RESUMO

In this study, a plant metabonomics technique, utilizing ultra-high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI--QTOF), was used to clarify the differences of various processed Bupleurum scorzonerifolium Willd. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to determine the differences in raw and different processed B. scorzonerifolium samples, including vinegar stir-fry, wine stir-fry, honey stir-fry, honey bran stir-fry and charcoal stir-fry. Thus, 39 significant compounds, e.g., saponins, free fatty acids, fatty acid pentitol glycosides, organic acid and linalool glycosides, were clearly or tentatively identified by UPLC-ESI--QTOF-MS/MS fragmentation pathways and by comparison with available reference standards. Most importantly, fatty acid pentitol glycosides were discovered and identified in B. scorzonerifolium for the first time. Furthermore, a HepG2 hepatitis model induced by TNF-α was used to measure the anti-hepatitis effect of raw and processed B. scorzonerifolium in vitro. Molecular docking was used to understand the interaction of key Q-markers with the active sites of the target protein. The results show that the UPLC-QTOF-MS metabolomics coupled with molecular docking is a powerful tool to quickly identify quality control characteristics of B. scorzonerifolium and its products.


Assuntos
Bupleurum , Saponinas , Bupleurum/química , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Graxos , Metabolômica/métodos , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem/métodos
10.
Microvasc Res ; 143: 104384, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35618036

RESUMO

AIMS: Inflammation is a key feature of endothelial dysfunction induced by angiotensin (Ang) II. The purpose of this study was to explore the role of Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in endothelial dysfunction in Ang II-induced hypertension. MATERIALS AND METHODS: We analyzed blood pressure and vascular function of wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice, treated with Ang II. In vitro, we mainly tested the endothelial nitric oxide synthase (eNOS) phosphorylation expression of human umbilical vein endothelial cells (HUVECs). KEY FINDINGS: Here we showed that 14-day Ang II infusion into mice resulted in the elevation of blood pressure, NLRP3 expression, serum interleukin (IL)-1ß level, and the decline of endothelium-dependent relaxation function, p-eNOS-Ser1177 expression in aortas. Nlrp3 deficiency reduced Ang II-induced blood pressure elevation and endothelial dysfunction. In vitro, NLRP3 was involved in the effect of Ang II on reducing p-eNOS-Ser1177 expression. Moreover, the direct effect of IL-1ß on vascular endothelial injury could be observed in both vivo and vitro. SIGNIFICANCE: Our result demonstrates that the NLRP3 inflammasome is critically involved in the detrimental effects of Ang II on vascular endothelium in hypertension via the activation of IL-1ß, placing NLRP3 as a potential target for therapeutic interventions in conditions with endothelial dysfunction in hypertension.

11.
BMC Psychiatry ; 22(1): 336, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35570282

RESUMO

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic, a major public health crisis, harms individuals' mental health. This 3-wave repeated survey aimed to examine the prevalence and correlates of suicidal ideation at different stages of the COVID-19 pandemic in a large sample of college students in China. METHODS: Using a repeated cross-sectional survey design, we conducted 3 online surveys of college students during the COVID-19 pandemic at 22 universities in Guandong, China. The 3 surveys were conducted during the outbreak period (T1: 3 February to 10 February 2020, N = 164,101), remission period (T2: 24 March to 3 April 2020, N = 148,384), and normalized prevention and control period (T3: 1 June to 15 June 2020, N = 159,187). Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. A range of suicide-related factors was assessed, including sociodemographic characteristics, depression, anxiety, insomnia, pre-existing mental health problems, and COVID-19-related factors. RESULTS: The prevalence of suicidal ideation was 8.5%, 11.0% and 12.6% at T1, T2, and T3, respectively. Male sex (aOR: 1.35-1.44, Ps < 0.001), poor self-perceived mental health (aOR: 2.25-2.81, Ps < 0.001), mental diseases (aOR: 1.52-2.09, P < 0.001), prior psychological counseling (aOR: 1.23-1.37, Ps < 0.01), negative perception of the risk of the COVID-19 epidemic (aOR: 1.14-1.36, Ps < 0.001), depressive symptoms (aOR: 2.51-303, Ps < 0.001) and anxiety symptoms (aOR: 1.62-101.11, Ps < 0.001) were associated with an increased risk of suicidal ideation. CONCLUSION: Suicidal ideation appeared to increase during the COVID-19 pandemic remission period among college students in China. Multiple factors, especially mental health problems, are associated with suicidal ideation. Psychosocial interventions should be implemented during and after the COVID-19 pandemic to reduce suicide risk among college students.


Assuntos
COVID-19 , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Humanos , Masculino , Pandemias , Prevalência , Fatores de Risco , SARS-CoV-2 , Estudantes/psicologia , Ideação Suicida
12.
Asian J Surg ; 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35599113

RESUMO

BACKGROUND AND OBJECTIVES: Post-hepatectomy liver failure (PHLF) is one of the most serious complications after hepatectomy in patients with hepatocellular carcinoma (HCC), and has an association with high morbidity and mortality. This study aimed to explore the risk factors of PHLF and to establish and validate a nomogram to predict PHLF. METHODS: We retrospectively analyzed 971 HCC patients undergoing major liver resection at the Eastern Hepatobiliary Surgery Hospital between 2011 and 2016, and established a nomogram based on multivariate analyses for predicting PHLF. The predictive accuracy and discriminative ability of the nomogram were evaluated by concordance index (C-index) and calibration curve. The predictive ability of PHLF of this nomogram was compared with conventional models using receiver operating characteristic (ROC) curves. RESULTS: The incidence of PHLF was 18.8%. Multivariate analysis identified age, BMI, preoperative ascites, preoperative prealbumin, spleen volume-to-platelet ratio, total bilirubin, and intraoperative blood loss as independent predictors of PHLF. The area under ROC curve (AUROC) of the predictive model was 0.668 and was higher than that of the albumin-bilirubin score (ALBI). The optimal cut-off value of the model was 124. CONCLUSIONS: We constructed a nomogram for predicting PHLF based on risk factors. The nomogram can assist clinicians in identifying patients with high-risk PHLF, eventually facilitating earlier interventions and improving clinical outcomes.

13.
Neurosci Bull ; 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35590012

RESUMO

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.

14.
Mol Ther Methods Clin Dev ; 25: 461-475, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35615707

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), characterized by inflammation and demyelination. Presently, repeated relapses of MS necessitate long-term immune-regulatory therapy. Blocking the CD28-B7 and CD40-CD40L costimulatory pathways is an effective and synergistic method for the prevention and amelioration of clinical symptoms of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. In this study, to explore the efficacy and safety of MS gene therapy, we used adeno-associated virus (AAV) as a vector to deliver CTLA4-immunoglobulin (Ig) or CD40-Ig on the EAE induced by myelin oligodendrocyte glycoprotein (MOG). Our results showed that a single administration of AAV8-CTLA4-Ig, either alone or with AAV8-CD40-Ig, protected mice from EAE and reversed disease progression. Decreased CD4+ and CD8+ T cell infiltration, inhibition of MOG antibody response, and downregulation of neuroinflammation were observed in mice receiving AAV, suggesting that autoimmunity was suppressed in EAE pathology. Moreover, no hematological or hepatic toxicity was observed in AAV-treated mice. Thus, compared with treatment with recombinant CTLA4-Ig (belatacept), AAV gene therapy could effectively control clinical symptoms and suppress autoimmunity in the long term. In summary, our study provides a potential therapeutic method for blocking T cell costimulation for the treatment of MS via gene therapy.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35613061

RESUMO

The pandemic of COVID-19 has become a global crisis in public health, which has led to a massive number of deaths and severe economic degradation. To suppress the spread of COVID-19, accurate diagnosis at an early stage is crucial. As the popularly used real-time reverse transcriptase polymerase chain reaction (RT-PCR) swab test can be lengthy and inaccurate, chest screening with radiography imaging is still preferred. However, due to limited image data and the difficulty of the early-stage diagnosis, existing models suffer from ineffective feature extraction and poor network convergence and optimisation. To tackle these issues, a segmentation-based COVID-19 classification network, namely SC2Net, is proposed for effective detection of the COVID-19 from chest x-ray (CXR) images. The SC2Net consists of two subnets: a COVID-19 lung segmentation network (CLSeg), and a spatial attention network (SANet). In order to supress the interference from the background, the CLSeg is first applied to segment the lung region from the CXR. The segmented lung region is then fed to the SANet for classification and diagnosis of the COVID-19. As a shallow yet effective classifier, SANet takes the ResNet-18 as the feature extractor and enhances highlevel feature via the proposed spatial attention module. For performance evaluation, the COVIDGR 1.0 dataset is used, which is a high-quality dataset with various severity levels of the COVID-19. Experimental results have shown that, our SC2Net has an average accuracy of 84.23% and an average F1 score of 81.31% in detection of COVID-19, outperforming several state-of-the-art approaches.

16.
Food Funct ; 13(12): 6613-6622, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35622066

RESUMO

Phloretin is a dihydrochalcone flavonoid from natural plants, which has protective activities against oxidative stress and inflammation. To date, its effect on diabetic nephropathy (DN) has not been investigated. In this study, we examined the potential role of phloretin in diabetes-induced renal damage and associated mechanisms in a type 2 diabetes mellitus (T2DM) model induced by streptozotocin (STZ) and high-fat diet (HFD) in Apolipoprotein E knockout (ApoE-/-) mice. We found that daily treatment with a low dose (20 mg kg-1) of phloretin, as a dietary supplement, significantly alleviated polyuria, proteinuria, and glomerular histopathological changes in the T2DM mice, indicating a protective effect of phloretin on diabetic renal dysfunction. In the phloretin-treated T2DM mice, major metabolic parameters, including blood glucose levels, were not altered significantly, suggesting that the observed beneficial effects of phloretin may be due to a mechanism independent of blood glucose control. Further experiments revealed that phloretin had a protective effect on glomerular podocytes as indicated by ameliorated glomerular basement membrane (GBM) thickening and podocyte foot process effacement. Moreover, phloretin treatment restored levels of nephrin and podocin, two podocyte slit diaphragm proteins that were decreased in T2DM mice. Our results indicate that low-dose phloretin treatment has a protective effect on podocytes in DN via a non-hypoglycemic mechanism in preserving nephrin and podocin expression levels. These data suggest that phloretin may be exploited as a novel therapeutic agent for DN.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Podócitos , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Camundongos , Floretina/farmacologia , Floretina/uso terapêutico , Podócitos/metabolismo , Podócitos/patologia
17.
Molecules ; 27(10)2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35630610

RESUMO

Polyhedral oligomeric silsesquioxane (POSS) has a nanoscale silicon core and eight organic functional groups on the surface, with sizes from 0.7 to 1.5 nm. The three-dimensional nanostructures of POSS can be used to build all types of hybrid materials with specific performance and controllable nanostructures. The applications of POSS-based fluorescent materials have spread across various fields. In particular, the employment of POSS-based fluorescent materials in sensing application can achieve high sensitivity, selectivity, and stability. As a result, POSS-based fluorescent materials are attracting increasing attention due to their fascinating vistas, including unique structural features, easy fabrication, and tunable optical properties by molecular design. Here, we summarize the current available POSS-based fluorescent materials from design to sensing applications. In the design section, we introduce synthetic strategies and structures of the functionalized POSS-based fluorescent materials, as well as photophysical properties. In the application section, the typical POSS-based fluorescent materials used for the detection of various target objects are summarized with selected examples to elaborate on their wide applications.


Assuntos
Nanoestruturas , Compostos de Organossilício , Corantes , Nanoestruturas/química , Compostos de Organossilício/química
18.
Sensors (Basel) ; 22(10)2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35632367

RESUMO

In the current work, we studied the sensing process of the sensor (E)-2-((quinolin-8ylimino) methyl) phenol (QP) for fluoride anion (F-) with a "turn on" fluorescent response by density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations. The proton transfer process and the twisted intramolecular charge transfer (TICT) process of QP have been explored by using potential energy curves as functions of the distance of N-H and dihedral angle C-N=C-C both in the ground and the excited states. According to the calculated results, the fluorescence quenching mechanism of QP and the fluorescent response for F- have been fully explored. These results indicate that the current calculations completely reproduce the experimental results and provide compelling evidence for the sensing mechanism of QP for F-.


Assuntos
Fluoretos , Bases de Schiff , Ânions , Modelos Moleculares , Prótons
19.
Mol Biol Evol ; 39(5)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35485492

RESUMO

The antibiotic resistance crisis continues to threaten human health. Better predictions of the evolution of antibiotic resistance genes could contribute to the design of more sustainable treatment strategies. However, comprehensive prediction of antibiotic resistance gene evolution via laboratory approaches remains challenging. By combining site-specific integration and high-throughput sequencing, we quantified relative growth under the respective selection of cefotaxime or ceftazidime selection in ∼23,000 Escherichia coli MG1655 strains that each carried a unique, single-copy variant of the extended-spectrum ß-lactamase gene blaCTX-M-14 at the chromosomal att HK022 site. Significant synergistic pleiotropy was observed within four subgenic regions, suggesting key regions for the evolution of resistance to both antibiotics. Moreover, we propose PEARP and PEARR, two deep-learning models with strong clinical correlations, for the prospective and retrospective prediction of blaCTX-M-14 evolution, respectively. Single to quintuple mutations of blaCTX-M-14 predicted to confer resistance by PEARP were significantly enriched among the clinical isolates harboring blaCTX-M-14 variants, and the PEARR scores matched the minimal inhibitory concentrations obtained for the 31 intermediates in all hypothetical trajectories. Altogether, we conclude that the measurement of local fitness landscape enables prediction of the evolutionary trajectories of antibiotic resistance genes, which could be useful for a broad range of clinical applications, from resistance prediction to designing novel treatment strategies.


Assuntos
Infecções por Escherichia coli , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , beta-Lactamases/genética
20.
Front Physiol ; 13: 850951, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480046

RESUMO

Beat-by-beat arrhythmia detection in ambulatory electrocardiogram (ECG) monitoring is critical for the evaluation and prognosis of cardiac arrhythmias, however, it is a highly professional demanding and time-consuming task. Current methods for automatic beat-by-beat arrhythmia detection suffer from poor generalization ability due to the lack of large-sample and finely-annotated (labels are given to each beat) ECG data for model training. In this work, we propose a weakly supervised deep learning framework for arrhythmia detection (WSDL-AD), which permits training a fine-grained (beat-by-beat) arrhythmia detector with the use of large amounts of coarsely annotated ECG data (labels are given to each recording) to improve the generalization ability. In this framework, heartbeat classification and recording classification are integrated into a deep neural network for end-to-end training with only recording labels. Several techniques, including knowledge-based features, masked aggregation, and supervised pre-training, are proposed to improve the accuracy and stability of the heartbeat classification under weak supervision. The developed WSDL-AD model is trained for the detection of ventricular ectopic beats (VEB) and supraventricular ectopic beats (SVEB) on five large-sample and coarsely-annotated datasets and the model performance is evaluated on three independent benchmarks according to the recommendations from the Association for the Advancement of Medical Instrumentation (AAMI). The experimental results show that our method improves the F 1 score of supraventricular ectopic beats detection by 8%-290% and the F1 of ventricular ectopic beats detection by 4%-11% on the benchmarks compared with the state-of-the-art methods of supervised learning. It demonstrates that the WSDL-AD framework can leverage the abundant coarsely-labeled data to achieve a better generalization ability than previous methods while retaining fine detection granularity. Therefore, this framework has a great potential to be used in clinical and telehealth applications. The source code is available at https://github.com/sdnjly/WSDL-AD.

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