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1.
Talanta ; 222: 121525, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33167235

RESUMO

The expression levels of matrix metalloproteinases (MMPs) are closely related to the degree of inflammation which facilitates tumor cells' invasion and migration. A tricolor fluorescence nanoprobe based on high-fidelity gold-selenium (Au-Se) nanoplatform was designed and constructed for simultaneously imaging matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) to thoroughly investigate the tumor cells' invasion and migration behaviors under inflammation environment. The nanoprobe was assembled by attaching Au NPs with three different peptide substrates respectively labeled with fluorescein isothiocyanate (FITC), 5-carboxytetramethylrhodamine (5-TAMRA) and cyanine 5 (Cy5) via the Au-Se bond. The nanoprobe can specifically respond to MMP-2/7/9, thereby triggering the fluorophores' fluorescence that quenched previously by fluorescence resonance energy transfer (FRET) to realize the MMP-2/7/9's visualization in biological systems. Moreover, as the inflammation stimulated by different concentrations lipopolysaccharide (LPS), the expression of MMP-2/7/9 in SMMC-7721 cells was observed to be significantly enhanced by confocal laser scanning microscope (CLSM) imaging, and inflammation was further proved to intensify SMMC-7721 cells' invasion and migration by transwell invasion and migration experiments. Therefore, the nanoprobe can be used to monitor biomarkers to provide a visual system for the degree of invasion and migration of tumor cells in an inflammatory environment, and also offer a new strategy for the study of the correlation between various active biomacromolecules and specific intracellular pathways in cells.

2.
Gene ; 765: 145114, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32891769

RESUMO

The current study aimed to investigate the role and underlying mechanisms of circ_LARP4 in diabetic nephropathy (DN). Here, mouse mesangial cells (SV40-MES13) were cultured with 30 mM glucose to establish a DN cellular model. The qRT-PCR results indicated that circ_LARP4 expression was downregulated in the DN cellular model compared to that in the control cells. As determined by an MTT assay, circ_LARP4 overexpression via the circ_LARP4 overexpression (OE) plasmids inhibited the cell proliferation rate. As determined by an Annexin V/PI kit and flow cytometry, circ_LARP4 overexpression increased the cell apoptosis rate. As measured by Western blot, circ_LARP4 overexpression enhanced BAX expression but reduced Bcl-2 expression, also suggesting an enhancement of cell apoptosis. Moreover, regarding cell fibrosis, circ_LARP4 overexpression reduced the mRNA levels of fibrosis markers, including fibronectin, collagen I and collagen IV. Interestingly, miR-424 was found to be reduced in the DN cellular model after transfection with the circ_LARP4 OE plasmids. In addition, restoration of miR-424 expression with the miR-424 mimics reversed the negative effects of circ_LARP4 overexpression on cell proliferation and fibrosis. In conclusion, circ_LARP4 was lower in the DN cellular model than in normal cells, and circ_LARP4 overexpression resulted in decreased cell proliferation and cell fibrosis but increased cell apoptosis in the DN cellular model by sponging miR-424.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33188385

RESUMO

OBJECTIVES: Nowadays, real-world data can be used to improve currently available dosing guidelines and to support regulatory approval of drugs for use in neonates by overcoming practical and ethical hurdles. This proof-of-concept study aimed to assess the population pharmacokinetics of azlocillin in neonates using real-world data, to make subsequent dose recommendations and to test these in neonates with early-onset sepsis (EOS). METHODS: This prospective, open-label, investigator-initiated study of azlocillin in neonates with EOS was conducted using an adaptive two-step design. First, a maturational pharmacokinetic-pharmacodynamic model of azlocillin was developed, using an empirical dosing regimen combined with opportunistic samples resulting from waste material. Second, a Phase II clinical trial (ClinicalTrials.gov: NCT03932123) of this newly developed model-based dosing regimen of azlocillin was conducted to assure optimized target attainment [free drug concentration above MIC during 70% of the dosing interval ('70% fT>MIC')] and to investigate the tolerance and safety in neonates. RESULTS: A one-compartment model with first-order elimination, using 167 azlocillin concentrations from 95 neonates (31.7-41.6 weeks postmenstrual age), incorporating current weight and renal maturation, fitted the data best. For the second step, 45 neonates (30.3-41.3 weeks postmenstrual age) were subsequently included to investigate target attainment, tolerance and safety of the pharmacokinetic-pharmacodynamic model-based dose regimen (100 mg/kg q8h). Forty-three (95.6%) neonates reached their pharmacokinetic target and only two neonates experienced adverse events (feeding intolerance and abnormal liver function), possibly related to azlocillin. CONCLUSIONS: Target attainment, tolerance and safety of azlocillin was shown in neonates with EOS using a pharmacokinetic-pharmacodynamic model developed with real-world data.

4.
Biomater Sci ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33211787

RESUMO

Drug-induced tissue injury has become a growing public health problem. Gastrointestinal injury and liver dysfunction are the most common side effects related to drug therapies, resulting in high morbidity and mortality in recent years. The overproduction of reactive oxygen species (ROS) is critically involved in the pathogenesis of drug-induced tissue injury. Consequently, antioxidant therapy represents a very promising strategy for the treatment of drug-induced tissue injury. Herein, a multifunctional antioxidant nanotherapy (TON) is engineered from a cyclodextrin-derived ROS-responsive material and a radical scavenger tempol, and is capable of eliminating a broad spectrum of ROS. After oral administration, TON can passively accumulate in the inflamed gastrointestinal tissues in mice with indomethacin-induced gastrointestinal injury. Correspondingly, TON shows superior efficacy in two representative murine models of indomethacin-induced gastrointestinal injury and acetaminophen-induced hepatic injury via attenuating oxidative stress and mitigating inflammatory responses. Additionally, preliminary in vitro and in vivo experiments demonstrate the good safety profile of TON. Consequently, the ROS-responsive antioxidant nanotherapy TON is promising for the treatment of drug-induced tissue and organ injury.

5.
Appl Radiat Isot ; : 109509, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33214023

RESUMO

Exploring the spatial distribution of the energy loss of ionising radiation at the subcellular level is indispensable for evaluating the radiobiological effects of targeted radionuclide therapy accurately. Believing that S-values are important for obtaining the target dose, the Committee on Medical Internal Radiation Dose (MIRD) proposed a method to obtain the cellular dosimetric parameter. However, most available data on cellular S-values were calculated based on simple geometric models, such as ellipsoids or spheres, which do not accurately reflect biological reality. To investigate the influence of the cellular model on S-values, calculations were performed for two kinds of polygon-surface phantom models of realistic, individual human cells, the lung epithelial cell model (the B2B Phantom model) and the hepatocyte model (the Liver Phantom model), using the Monte Carlo (MC) software package GATE. To analyse the influence of cell geometry on the final S-value, the differences in the S-values between the realistic cell models and simple geometric sphere and ellipsoid models with similar volumes were calculated and compared for six different combinations of source and target regions. The irradiation conditions were 0.01-1.10 MeV monoenergetic electron sources and the Auger electronic therapy nuclides Ga-67, Tc-99m, In-111, I-125 and Tl-201, which are commonly used in nuclear medicine. The S-values calculated in this study are different from the results of the simple geometry models proposed by previous researchers. Two more precise polygon-surface phantom models of realistic, individual human cells were used, which provided more accurate information about the cell dose and will be very useful for the diagnostic application of radiotherapy in the future.

6.
Anal Chem ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33210902

RESUMO

Homocysteine (Hcy) is one of the important biomarkers of clinical diagnosis, which is closely related to the occurrence and development of many diseases. Current analysis methods have difficulties in detecting Hcy in cells and living organisms. As a powerful technique, fluorescence methods combined the laser confocal imaging technology can achieve real-time visual tracking in cells and in vivo. Herein, we establish a conjugated copolymer-based fluorescence nanosensor (DPA-PFNP-Cu(II)) using the connected 2,7-dibromofluorene and 4,7-bis (2-bromothiophen-5-yl)-2-1-3-benzothiadiazole as the main chain. The competitive coordination between Hcy and Cu(II) allows the fluorescence of the polymer off to on. Finally, the nanosensor is applied for in situ imaging of Hcy levels in the kidney and liver of diabetic mice and is found that Hcy levels were positively correlated with the degree of diabetes. Notably, the depth of tissue penetration of the nanosensor enables Hcy detection of the liver and kidney through in vivo imaging without damage. Two-photon imaging and in vivo imaging achieve consistent results, which correct each other, improving the accuracy of the test result. The present works provide a new imaging technique for studying the occurrence and development of diabetes and screening of new drugs for treatment at the living level.

7.
Nat Commun ; 11(1): 5662, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168832

RESUMO

Unlike the well-reported 1,2-difunctionalization of alkenes that is directed by classic pyridine and imine-containing directing groups, oxo-palladacycle intermediates featuring weak Pd-O coordination have been less demonstrated in C-H activated cascade transformations. Here we report a quadruple C-H activation cascade as well as hydro-functionalization, C-H silylation/borylation sequence based on weakly coordinated palladium catalyst. The hydroxyl group modulates the intrinsic direction of the Heck reaction, and then acts as an interrupter that biases the reaction away from the classic ß-H elimination and toward C-H functionalization. Mechanistically, density functional theory calculation provides important insights into the key six-membered oxo-palladacycle intermediates, and indicates that the ß-H elimination is unfavorable both thermodynamically and kinetically. In this article, we focus on the versatility of this approach, which is a strategic expansion of the Heck reaction.

8.
J Mater Chem B ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174584

RESUMO

Inflammation is ubiquitous in the body, and uncontrolled inflammation often contributes to various diseases. Celastrol, a compound isolated from a Chinese medicinal herb, holds great potential in treating multiple inflammation-associated diseases. However, its further clinical use is limited by its poor solubility, bioavailability, and high organ toxicity. With the advancement of nanotechnology, the nano-delivery of celastrol can effectively improve its oral bioavailability, maximize its efficacy and minimize its side effects. Here, we summarize the roles of celastrol in the treatment of various inflammation-associated diseases, with a special emphasis on its role in modulating immune cell signaling or non-immune cell signaling within the inflammatory microenvironment, and we highlight the latest advances in nano-delivery strategies for celastrol to treat diseases associated with inflammation.

9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1596-1599, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018299

RESUMO

The difficulty of applying deep learning algorithms to biomedical imaging systems arises from a lack of training images. An existing workaround to the lack of medical training images involves pre-training deep learning models on ImageNet, a non-medical dataset with millions of training images. However, the modality of ImageNet's dataset samples consisting of natural images in RGB frequently differs from the modality of medical images, consisting largely of images in grayscale such as X-ray and MRI scan imaging. While this method may be effectively applied to non-medical tasks such as human face detection, it proves ineffective in many areas of medical imaging. Recently proposed generative models such as Generative Adversarial Networks (GANs) are able to synthesize new medical images. By utilizing generated images, we may overcome the modality gap arising from current transfer learning methods. In this paper, we propose a training pipeline which outperforms both conventional GAN-synthetic methods and transfer learning methods.


Assuntos
Aprendizado Profundo , Imagem por Ressonância Magnética , Algoritmos , Humanos , Radiografia , Raios X
10.
Artigo em Inglês | MEDLINE | ID: mdl-33035165

RESUMO

Probabilistic power flow (PPF) calculation is an important power system analysis tool considering the increasing uncertainties. However, existing calculation methods cannot simultaneously achieve high precision and fast calculation, which limits the practical application of the PPF. This article designs a specific architecture of the extreme learning machine (ELM) in a model-driven pattern to extract the power flow features and therefore accelerate the calculation of PPF. ELM is selected because of the unique characteristics of fast training and less intervention. The key challenge is that the learning capability of the ELM for extracting complex features is limited compared with deep neural networks. In this article, we use the physical properties of the power flow model to assist the learning process. To reduce the learning complexity of the power flow features, the feature decomposition and nonlinearity reduction method is proposed to extract the features of the power flow model. An enhanced ELM network architecture is designed. An optimization model for the hidden node parameters is established to improve the learning performance. Based on the proposed model-driven ELM architecture, a fast and accurate PPF calculation method is proposed. The simulations on the IEEE 57-bus and Polish 2383-bus systems demonstrate the effectiveness of the proposed method.

11.
J Bacteriol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077630

RESUMO

The gut microbiota plays a crucial role in the development of the immune system and confers benefits or disease susceptibility to the host. Emerging studies have indicated that the gut microbiota could affect pulmonary health and disease through cross-talk between the gut microbiota and the lungs. Gut microbiota dysbiosis could lead to acute or chronic lung disease, such as asthma, tuberculosis and lung cancer. In addition, the composition of the gut microbiota may be associated with different lung diseases, the prevalence of which also vary by age. Modulation of the gut microbiota through short-chain fatty acids, probiotics and micronutrients may present potential therapeutic strategies to protect against lung diseases. In this review, we will provide an overview of the cross-talk between the gut microbiota and the lungs as well as elucidate the underlying pathogenesis or potential therapeutic strategies of some lung diseases from the point of view of the gut microbiota.

12.
J Surg Res ; 258: 162-169, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011447

RESUMO

BACKGROUND: Laparoscopic pancreatoduodenectomy (LPD) is a minimally invasive technique widely developed in the last few decades. Although magnetic compression anastomosis (magnamosis) is used during cholangiojejunostomy, its applicability in LPD has not yet been reported. Herein, we evaluated the feasibility and effectiveness of magnamosis in LPD. METHODS: Between January 2018 and December 2019, seven patients who underwent laparoscopic magnetic compression choledochojejunostomy (LMC-CJ) or laparoscopic magnetic compression pancreatojejunostomy (LMC-PJ) in LPD were enrolled. After LPD, a parent magnet with or without a drainage tube was placed in the proximal bile duct and pancreatic duct of each patient. Daughter magnets were introduced to couple with the parent magnets at the desired sites. A close postoperative surveillance of magnet movements was performed. Various relevant data were collected, and all patients were followed up until February 2020. RESULTS: LPD was successfully completed in all seven patients, of which seven underwent LMC-CJ and two received LMC-PJ. The median time needed for completion of LMC-CJ was 11 min (range, 8-16). The cost time for the two cases of LMC-PJ was 12 and 15 min, respectively. After a median time of 50 d (range, 40-170) postoperation, all magnets were expelled. No leakages of LMC-CJ or LMC-PJ were observed after operation. After a median follow-up period of 11 mo (range, 4-18), there was no incidence of anastomotic stricture.

13.
Chem Commun (Camb) ; 56(79): 11827-11830, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021254

RESUMO

Herein, novel coin tree-like TiO2 moieties with lots of anatase-rutile phase junctions were constructed by a general, simple, and environmentally friendly strategy. The anatase/rutile ratios can be easily tuned by changing the ratios of the two H-bond donors. Owing to this featured shape, the TiO2 sample displays robust photocatalytic activity and better stability.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33021459

RESUMO

Background: Giant inguinal hernia (GIH) is a rare disease but it can cause serious complications, such as intestinal obstruction and strangulation. Few studies have explored surgical treatment with respect to the transabdominal preperitoneal (TAPP) approach or measures to reduce the occurrence of postoperative seroma. Purpose: To investigate the safety and efficacy of the TAPP approach with negative pressure drainage in GIHs. Methods: From January 2017 to December 2019, 32 patients who underwent TAPP procedures with negative pressure drainage for GIHs at our hospital were reviewed. Demographic information, surgical characteristics, and follow-up data were obtained. Results: The mean age of the patients was 66, and more than half of them had medical comorbidities. All GIHs were defined as Type 1 and were successfully repaired through the TAPP approach with negative pressure drainage. The mean operative time was 146 minutes (range 122-251). After surgery, the mean drainage time was 7 days (range 5-10 days), and the mean volume of drainage in each patient was 820 mL (range 655-1020 mL). Complications occurred in 3 cases. For 1 case, the inferior epigastric artery was injured during surgery. A seroma was observed in 1 patient, which occurred 2 days after removal of the drainage tube. Finally, 1 patient developed an umbilical puncture site infection, and the wound healed after changing the dressing. The mean follow-up was 13 months (range 1-32), and there was no recurrence or mesh infection during that time. Conclusion: TAPP is a safe and effective approach for treating Type 1 GIHs with low operative complications. Negative pressure drainage through the scrotum to the preperitoneal space may reduce the incidence of seroma. Recurrence of hernias was not observed, and chronic pain seldom occurred during the follow-up period in our study.

15.
Chem Commun (Camb) ; 56(88): 13653-13656, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33063811

RESUMO

A novel copper-catalyzed sulfur dioxide anion incorporation cascade for the synthesis of 1-thiaflavanone sulfones has been disclosed using rongalite as an economic and safe sulfone source. A series of 1-thiaflavanone sulfones were synthesized from easily prepared 2'-iodochalcone derivatives in excellent yields. This transformation proceeds through consecutive formation of two C-S bonds, which is the first example of SO- being used to construct sulfone motifs under copper-catalyzed conditions.

16.
Chem Commun (Camb) ; 56(91): 14267-14270, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33124634

RESUMO

We demonstrate here that a porphyrin covalent organic framework-based nanoplatform could effectively avoid the interference of proteins and biothiols and result in high-fidelity signals in intracellular mRNA imaging.

17.
Chem Commun (Camb) ; 56(90): 14083-14086, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33107876

RESUMO

A simple catalyst of Ni(OAc)2 and P(t-Bu)3 enables selective C-alkylation of thioacetamides and primary acetamides with alcohols for the first time. Monoalkylation of thioamides, amides and t-butyl esters occurs in excellent yields (>95%). Mechanistic studies reveal that the reaction proceeds via a hydrogen autotransfer pathway.

18.
J Cell Mol Med ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009725

RESUMO

Diabetic nephropathy (DN) is a serious kidney disease resulted from diabetes. Dys-regulated proliferation and extracellular matrix (ECM) accumulation in mesangial cells contribute to DN progression. In this study, we tested expression level of MIAT in DN patients and mesangial cells treated by high glucose (HG). Up-regulation of MIAT was observed in DN. Then, functional assays displayed that silence of MIAT by siRNA significantly repressed the proliferation and cycle progression in mesangial cells induced by HG. Meanwhile, we found that collagen IV, fibronectin and TGF-ß1 protein expression was obviously triggered by HG, which could be rescued by loss of MIAT. Then, further assessment indicated that MIAT served as sponge harbouring miR-147a. Moreover, miR-147a was decreased in DN, which exhibited an antagonistic effect of MIAT on modulating mesangial cell proliferation and fibrosis. Moreover, bioinformatics analysis displayed that E2F transcription factor 3 (E2F3) could act as direct target of miR-147a. We demonstrated that E2F3 was greatly increased in DN and the direct binding association between miR-147a and E2F3 was evidenced using luciferase reporter assay. In summary, our data explored the underlying mechanism of DN pathogenesis validated that MIAT induced mesangial cell proliferation and fibrosis via sponging miR-147a and regulating E2F3.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33122077

RESUMO

OBJECTIVE: Endovascular treatment with percutaneous transluminal angioplasty and stenting has quickly gained popularity for treatment of deep venous obstructive disease. Early thrombosis after stenting in iliofemoral veins is uncommon. The treatment and analysis of the underlying factors leading to the rethrombosis of stents placed in the previous 14 days are reported in this study. METHODS: Patients diagnosed with early in-stent thrombosis after iliofemoral stenting were reviewed in this retrospective analysis. Patients with acute occlusion were routinely treated by catheter-directed thrombolysis (CDT), and the underlying causes of early occlusion were identified during the procedure. After successful CDT procedures, patients received additional interventions (percutaneous transluminal angioplasty with or without stenting) if indicated. RESULTS: A total of 527 patients underwent stenting in the iliofemoral veins, and 32 patients (20 men [63%]) with acute thrombosis in iliofemoral venous stents placed in the previous 14 days were treated in our center from January 2015 to December 2018. The mean time from the onset of symptoms to the intervention was 6 days. Successful thrombolysis was achieved in 31 of the 32 patients, and additional stents were implanted in 16 patients. Patency was achieved in all cases. The underlying factors of early stent thrombosis were technical failure of the initial procedure, such as suboptimal positioning, failure owing to stent characteristics (stent kinking, compression, and angulation), in-stent residual thrombus, and inadequate anticoagulation. In all cases, recanalization was achieved through successful thrombolysis with or without restenting. CONCLUSIONS: Treatment with CDT and stenting of early in-stent thrombosis is effective and feasible. Recanalization of stented segment(s) can be achieved in most cases of recent thrombosis (<14 days). Early stent-related occlusion is mainly caused by stent-related problems and technical inadequacies.

20.
Org Lett ; 22(21): 8278-8284, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33044081

RESUMO

A nickel-catalyzed enantioselective transfer hydrogenation and deuteration of N-sulfonyl imines was developed. Excellent α-selectivity and high deuterium content were achieved by using inexpensive 2-propanol-d8 as a deuterium source. As a highlight, no deuteration of ß-C-H and the remote C-H of N-sulfonyl amines occurred, which is hard to achieve using other imines or by hydrogen isotope exchange with D2O. Mechanism studies indicated a stepwise pathway through the [Ni-D] intermediate.

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