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1.
J Org Chem ; 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32478514

RESUMO

The NH4I-triggered formal [4 + 2] annulation of α,ß-unsaturated ketoxime acetates with N-acetyl enamides has been developed. The current protocol employs electron-rich enamides as C2 synthons and enables the efficient and straightforward construction of polysubstituted pyridines in moderate to good yields based on metal-free systems. The reaction tolerates a wide range of functional groups and represents an alternate route towards the synthesis of pyridine derivatives.

2.
Chem Biol Drug Des ; 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32418370

RESUMO

The emergence of New Delhi metal beta-lactamase (NDM-1) -producing bacteria and their worldwide spread pose great challenges for the treatment of drug-resistant bacterial infections. These bacteria can hydrolyze most ß-lactam antibacterials. Unfortunately, there are no clinically useful NDM-1 inhibitors. In the current work, we manually collected NDM-1 inhibitors reported in the past decade and established the first NDM-1 inhibitor database. Four machine learning models were constructed using the structural and property characteristics of the collected compounds as input training set to discover potential NDM-1 inhibitors. In order to distinguish between high active inhibitors and putative positive drugs, a three-classification strategy was introduced in our study. In detail, the commonly used positive and negative divisions are converted into strongly active, weakly active and inactive. The accuracy of the best prediction model designed based on this strategy reached 90.5%, compared with 69.14% achieved by the traditional docking-based virtual screening method. Consequently, the best model was used to virtually screen a natural product library. The safety of the selected compounds was analyzed by the ADMET prediction model based on machine learning. Seven novel NDM-1 inhibitors were identified, which will provide valuable clues for the discovery of NDM-1 inhibitors.

3.
Sci Total Environ ; 721: 137654, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32197285

RESUMO

Swine wastewater (SW) represents an important source of antibiotic resistance genes (ARGs) in the environment. However, few studies have assessed the occurrence and removal of ARGs in the whole wastewater treatment process followed by its farmland application. This study investigated the ARGs profiles in an integrated SW treatment system and its receiving soil, as well as their relationships with SW parameters and bacterial communities. Results revealed that sulfonamide, tetracycline and aminoglycoside resistance genes were dominant in SW. The relative abundance of total ARGs in SW was reduced by 84% after the treatments. Among the SW treatment units, anaerobic digestion, primary sedimentation and constructed wetland contributed to ARGs removal while secondary sedimentation increased the total ARGs abundance. Farmland irrigation of the treated SW resulted in enrichment of persistent ARGs in the receiving soil, which might be attributed to the propagation of potential bacterial hosts and high horizontal gene transferability. Redundancy analysis indicated that the relative abundance of total ARGs was significantly correlated with total nitrogen, total phosphorus, antibiotics and bacterial communities. The shift in bacterial community was the major driving factor for ARGs alteration during SW treatment process. Our results highlight the effect of treated SW irrigation on the antibiotic resistome in agricultural environment, and can contribute in improving SW treatment system for better antibiotic resistance control.

4.
Acta Pharmacol Sin ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152438

RESUMO

Endothelial-mesenchymal transition (EnMT) plays a pivotal role in various diseases, including pulmonary hypertension (PH), and transcription factors like Snail are key regulators of EnMT. In this study we investigated how these factors were regulated by PH risk factors (e.g. inflammation and hypoxia) in human umbilical vein endothelial cells (HUVECs). We showed that treatment with interleukin 1ß (IL-1ß) induced EnMT of HUVECs via activation of NF-κB/Snail pathway, which was further exacerbated by knockdown of protein tyrosine phosphatase L1 (PTPL1). We demonstrated that PTPL1 inhibited NF-κB/Snail through dephosphorylating and stabilizing IκBα. IL-1ß or hypoxia could downregulate PTPL1 expression in HUVECs. The deregulation of PTPL1/NF-κB signaling was validated in a monocrotaline-induced rat PH (MCT-PH) model and clinical PH specimens. Our findings provide novel insights into the regulatory mechanisms of EnMT, and have implications for identifying new therapeutic targets for clinical PH.

5.
Opt Lett ; 45(5): 1285-1288, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32108827

RESUMO

We present a photonic approach to generate and transmit a dual-chirp microwave waveform with antidispersion performance. Traditionally, the microwave signal generated based on double-sideband (DSB) modulation suffers from power fading significantly. We propose a DSB-based dual-chirp microwave waveform transmitter that can eliminate the chromatic dispersion-induced power fading (CDIP) over fiber transmission. The CDIP elimination, rather than compensation, ensures that the working bandwidth of the dual-chirp waveform is not limited by the periodical power fading. The proposed signal modulation scheme makes the signal transmitter free from the direct current bias drifting of the modulator. Moreover, thanks to the phase modulation, the generated waveform is background-free. The proposed dual-chirp waveform transmitter features a compact structure, polarization independence, and CDIP elimination, which has great potential in radars for one-to-multibase station fiber transmission.

6.
Proc Natl Acad Sci U S A ; 117(9): 4642-4652, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32071231

RESUMO

Placental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200 µg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals until embryonic day 12.5, whereupon placental samples were collected and compared with unexposed controls. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to a decrease in the area occupied by spongiotrophoblast relative to trophoblast giant cells (GCs) within the junctional zone, markedly reduced placental serotonin (5-HT) concentrations, and lowered 5-HT GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metabolite of serotonin, were increased. GC dopamine immunoreactivity was increased in BPA- and BPS-exposed placentas. A strong positive correlation between 5-HT+ GCs and reductions in spongiotrophoblast to GC area suggests that this neurotransmitter is essential for maintaining cells within the junctional zone. In contrast, a negative correlation existed between dopamine+ GCs and reductions in spongiotrophoblast to GC area ratio. These outcomes lead to the following conclusions. First, BPS exposure causes almost identical placental effects as BPA. Second, a major target of BPA/BPS is either spongiotrophoblast or GCs within the junctional zone. Third, imbalances in neurotransmitter-positive GCs and an observed decrease in docosahexaenoic acid and estradiol, also occurring in response to BPA/BPS exposure, likely affect the placental-brain axis of the developing mouse fetus.

7.
ChemSusChem ; 13(8): 2053-2059, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32012457

RESUMO

A novel and green route has been developed for the electrochemical synthesis of spiro[4.5]trienones through radical-initiated dearomative spirocyclization of alkynes with diselenides. This metal-free and oxidant-free electrosynthesis reaction was performed in an undivided cell under mild conditions. A variety of selenation spiro[4.5]trienones products were prepared in moderate-to-good yields, showing a broad scope and functional group tolerance. Moreover, the developed continuous-flow system combined with electrosynthesis possesses the potential to achieve scaled-up reactions, overcoming the low efficiency of conventional electrochemical scaled-up reactions.

8.
J Org Chem ; 85(4): 2532-2542, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31910622

RESUMO

The copper-catalyzed [4 + 2] annulation of α,ß-unsaturated ketoxime acetates with 1,3-dicarbonyl compounds for the synthesis of three classes of structurally diverse pyridines has been developed. This method employs 1,3-dicarbonyl compounds as C2 synthons and enables the synthesis of multifunctionalized pyridines with diverse electron-withdrawing groups in moderate to good yields. The mechanistic investigation suggests that the reactions proceed through an ionic pathway.

9.
Expert Opin Ther Targets ; 24(2): 147-153, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31971463

RESUMO

Introduction: Dipeptidyl-peptidase-4 (DPP-4) is a surface bound ectopeptidase that is commonly known as CD26 or adenosine deaminase binding protein. DPP-4 is membrane anchored but it can be cleaved by numerous proteases including matrix-metalloproteinases (MMPs). DPP-4 is expressed by endothelial and epithelial cells, the kidney, intestine and cells of the immune system; it has a broad spectrum of biological functions in immune regulation, cancer biology and glucose metabolism.Areas covered: This article sheds light on the functions of DPP-4, the molecular mechanisms that govern its expression, it's role in the pathogenesis of common respiratory illnesses and potential as a therapeutic target.Expert opinion: DPP-4 has a deleterious role in respiratory disease. Its biological functions, key molecular pathways, interactions and associations are slowly being elucidated. Progressing our knowledge of the role of this multi-faceted molecule may yield vital and novel therapies for respiratory diseases such as lung cancer, asthma, and chronic obstructive pulmonary disease (COPD).

10.
Plant Biotechnol J ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31916348

RESUMO

Tomato (Solanum lycopersicum L.) plants are cold-sensitive, and the fruit are susceptible to postharvest chilling injury when stored at low temperature. However, the mechanisms underlying cold stress responses in tomato are poorly understood. We demonstrate that SlGRAS4, encoding a transcription factor induced by low temperature, promotes chilling tolerance in tomato leaves and fruit. Combined genome-wide ChIP-seq and RNA-seq approaches identified among cold stress-associated genes those being direct targets of SlGRAS4 and protein studies revealed that SlGRAS4 forms a homodimer to self-activate its own promoter. SlGRAS4 can also directly bind tomato SlCBF promoters to activate their transcription without inducing any growth retardation. The study identifies the SlGRAS4-regulon as a new cold response pathway conferring cold stress tolerance in tomato independently of the ICE1-CBF pathway. This provides new track for breeding strategies aiming to improve chilling tolerance of cultivated tomatoes and to preserve sensory qualities of tomato fruit often deteriorated by storage at low temperatures.

11.
Environ Technol ; : 1-9, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31951776

RESUMO

Microalgal aggregation is a key for both microalgae harvesting and water purification, where changes in extracellular polymeric substance (EPS) secretion and cell motility changes are of core importance. In this study, we investigated the aggregation process of Chlamydomonas microsphaera confronting resource limitation and chlorine disinfection, and tried to compare changes in the magnitude of EPS secretion and cell motility. Results show that the presence of mild chlorine solution (0.20%) dose stimulated microalgal aggregation (with an aggregated to planktonic cells ratio of 3.2), with extracellular protein concentration and mean cell velocity reaching a maximum of 43.43 ± 0.01 mg/L and 201 ± 35 µm/s, respectively. These values are 71% and 191% higher than those of the control. Comparably, nutrient availability had only a limited impact on microalgal aggregation and was associated with mild EPS secretion and cell motility. Correlation analysis revealed a strong positive impact of cell motility (mean velocity) on microalgae aggregation, with little effect on EPS excretion. Together, these quantitative estimations may shed light on understanding the mechanisms of microalgae aggregation in aqueous systems, which could help future design and practical operation of source water pretreatment or microalgae harvesting.

12.
J Neurochem ; 152(3): 397-415, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31442326

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Its pathological features are dopaminergic neuronal death in the substantia nigra (SN), and significant reduction in dopamine (DA) content in the striatum. A large number of studies have found an increase in iron levels in PD patients and animal models, which suggested that brain iron metabolism dysfunction played a key role in the pathogenesis of PD. Lactoferrin (Lf) is a non-heme iron-binding glycoprotein belonging to the transferrin family, entering the cell membrane via a lactoferrin receptor-mediated pathway. Lf exists mainly in two forms: iron-free-lactoferrin (apo-Lf) and iron-saturated-lactoferrin (holo-Lf). Our previous studies found thatapo-Lf and holo-Lf exert neuroprotective effects against 1-methyl-4-phenylpyridinium toxicity in ventral mesencephalon neurons in vitro. This study aimed to further investigate whether two different forms of Lf have neuroprotective effects in vivo, and to examine their mechanisms, so as to provide an experimental basis for finding new therapeutic strategies against PD. In the central nervous system, Lf antagonized 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced DA depletion in the striatum, iron deposition, oxidative, and apoptotic processes in the SN. Lf treatment down-regulated iron import protein divalent metal transporter1 and up-regulated iron export protein ferroportin1, attenuating MPTP-induced accumulation of nigral iron level. In the peripheral system, Lf alleviated MPTP-induced increases in serum iron and ferritin, and decreases in serum total iron-binding capacity, loss of spleen weight, and reduction in spleen iron content. The results indicate that Lf has a neuroprotective effect on MPTP-induced PD model mice, and its mechanism may be related to anti-iron dysregulation, anti-oxidative stress, and anti-apoptosis, with apo-Lf showing greater efficacy. Therefore, Lf might be a promising therapeutic substance for PD. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/.

13.
Cell Biol Int ; 44(3): 785-794, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31774600

RESUMO

We investigated the effect of triptolide (TP) on spinal cord injury (SCI), and its underlying mechanism. Following the establishment of the SCI model using YFP H-line transgenic mice, TP was intraperitoneally injected at a dose of 0.2 mg/kg once daily for 7 days. Behavioral tests, Nissl staining, and hematoxylin-eosin staining were employed to assess motor function recovery and neuronal cell death. Western blot and immunofluorescence staining were used to assess autophagy-associated proteins (LC3B, p62, Beclin-1) and the apoptosis-associated proteins (Bcl-2, caspase-3, Bax). The TP-treated group showed improved motor functions, and reduced neuronal cell death. Also, significant upregulation of Bcl-2 and LC3B expressions, with the downregulation of p62, Bax and caspase-3 expressions were found in the TP-treated group. Additionally, phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1 and ERK2) was decreased in the TP-treated group. TP mediates its protective effect in SCI by promoting the autophagic pathway while inhibiting the MAPK/ERK1/2 signaling pathway. These results demonstrate the therapeutic potential of TP in SCI.

14.
Curr Top Med Chem ; 20(1): 78-85, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31820691

RESUMO

The advancement of cardiac surgery benefits from the continual technological progress of cardiopulmonary bypass (CPB). Every improvement in the CPB technology requires further clinical and laboratory tests to prove its safety and effectiveness before it can be widely used in clinical practice. In order to reduce the priming volume and eliminate a separate arterial filter in the CPB circuit, several manufacturers developed novel hollow-fiber membrane oxygenators with integrated arterial filters (IAF). Clinical and experimental studies demonstrated that an oxygenator with IAF could reduce total priming volume, blood donor exposure and gaseous microemboli delivery to the patient. It can be easily set up and managed, simplifying the CPB circuit without sacrificing safety. An oxygenator with IAF is expected to be more beneficial to the patients with low body weight and when using a minimized extracorporeal circulation system. The aim of this review manuscript was to discuss briefly the concept of integration, the current oxygenators with IAF, and the in-vitro / in-vivo performance of the oxygenators with IAF.


Assuntos
Desenho de Equipamento , Oxigênio/administração & dosagem , Oxigenadores de Membrana , Ponte Cardiopulmonar/instrumentação , Humanos , Nitrogênio
15.
J Cell Mol Med ; 24(2): 1208-1219, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31859410

RESUMO

Impairment of the oesophageal epithelium in patients with reflux oesophagitis (RE) is a cytokine-mediated injury rather than a chemical burn. The present study was conducted to explore CaSR/NLRP3 inflammasome pathway activation and cytokines IL-1ß and IL-18 release in oesophageal epithelia injured by refluxates and the effects of Tojapride on that signal regulation. Using a modified RE rat model with Tojapride administration and Tojapride-pretreated SV40-immortalized human oesophageal epithelial cells (HET-1A) exposed to acidic bile salts pretreated with Tojapride, we evaluated the therapeutic effects of Tojapride on oesophageal epithelial barrier function, the expression of CaSR/NLRP3 inflammasome pathway-related proteins and the release of downstream cytokines in response to acidic bile salt irritation. In vivo, Tojapride treatment ameliorated the general condition and pathological lesions of the oesophageal epithelium in modified RE rats. In addition, Tojapride effectively blocked the CaSR-mediated NLRP3 inflammasome activation in modified RE rats. In vitro, Tojapride treatment can reverse the harmful effect of acidic bile salts, which reduced transepithelial electrical resistance (TEER), up-regulated the CaSR-mediated NLRP3 inflammasome pathway and increased caspase-1 activity, LDH release and cytokines secretion. Taken together, these data show that Tojapride can prevent CaSR-mediated NLRP3 inflammasome activation and alleviate oesophageal epithelial injury induced by acidic bile salt exposure.

16.
J Cancer ; 10(27): 6801-6812, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839814

RESUMO

Background: Although it is widely accepted that invasive micropapillary carcinoma (IMPC) presents more aggressive behavior and has a higher aggressive behavior, the prognosis of IMPC compared with invasive ductal carcinoma (IDC) remains controversial. We conducted this study to explore gene expression profiles of IMPC and establish a competing nomogram that predicts the survival outcomes across these two groups of patients. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed. Propensity score matching (PSM) was used to adjust for potential baseline confounding between IMPC and IDC group. The Kaplan-Meier method was used to calculate the occurrence of overall mortality. The Gray method was used to estimate the rate of breast cancer specific death (BCSD). A competing regression model was used to evaluate factors associated with BCSD. A nomogram based on the competing risk regression model was established to predict individual outcomes. IMPC-specific gene expression profiles were explored using microarrays data from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed. Results: In this study, 330786 (99.62%) patients with IDC 1247 (0.38%) patients with IMPC were included. Patients with IMPC had more lymph node involvement and a larger tumor size compared with those with IDC. After PSM, many distributional differences were eliminated, showing that the IMPC and IDC group were more similar. Patients with IMPC had a favorable prognosis with statistical significance compared with patients with IDC (overall mortality HR = 0.68; 95%CI, 0.53-0.86; P = 0.002). Based on Gray method, patients with IMPC had a favorable prognosis with significant statistical significance compared with patients with IDC (BCSD SHR = 0.64; 95%CI, 0.47-0.88; P = 0.006). Multivariate analysis based on competing risk model demonstrated that IMPC was a favorable independent factor for BCSD. The nomogram could accurately predict BCSD with a high internal and external validated C-index (0.835, 0.818 respectively). A total of 53 upregulated differentially expressed genes (DEGs) and 40 downregulated DEGs of IMPC was identified. The GO analysis results showed that downregulated DEGs were significantly enriched in extracellular structure organization, extracellular matrix, cell-substrate adhesion junction. KEGG analysis of selective gene sets shows that downregulated DEGs significantly enriched for processes related to carbon metabolism, Rap1 signaling pathway. Conclusion: In the current study, IMPC accounted for 0.38% of the entire cohort. IMPC was found to be a favorable independent prognostic factor. The present study identified gene expression profiles and signal pathways of IMPC. The developed nomogram can help the oncologists to predict individual outcomes more accurately.

17.
J Coll Physicians Surg Pak ; 29(12): S126-S128, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31779765

RESUMO

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard therapy for patients with advanced non-small-cell lung cancer (NSCLC) harbouring common EGFR mutations. However, about 10% of EGFR mutations are uncommon mutations and their response to EGFR-TKIs remains unclear. The present case reports a 75-year, female patient with advanced NSCLC, presenting with a new subtype of EGFR exon 19 insertion mutation (IPVAIL insertion), who showed obvious symptom improvement after EGFR-TKIs treatment but a relatively short time of progression-free survival (PFS) and succumbed to tumor 133 days (4.4 months) after diagnosis. In conclusion, patients harbouring new subtype of EGFR exon 19 insertion mutations, IPVAIL insertion may have a poor prognosis. Further experiences are required to characterise these uncommon mutations.

18.
World J Clin Cases ; 7(21): 3590-3594, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31750342

RESUMO

BACKGROUND: Squamous cell carcinoma (SCC) of the nail bed is a poorly reported malignant subungual tumor. Because it presents with nonspecific symptoms and signs, it is frequently misdiagnosed by dermatologists or surgeons. A delay in diagnosis and/or wrong treatment might increase the possibility of disease progression. Thus, new perspectives are needed to assist dermatologists and surgeons with diagnosing and treating SCC. This rare case presented with a 2-year delay in the diagnosis of SCC teaches a valuable lesson. CASE SUMMARY: A 62-year-old female presented with a non-healing subungual growth in the nail bed of the right middle finger for 2 years. The lesion was first medicated with iodine by the patient herself without any relief. Twenty months later, a dermatologist diagnosed the lesion as paronychia and treated it with nail avulsions repeatedly with no obvious alleviation. A lesionectomy confirmed the lesion was SCC. An extended excision of the tumor with amputation of the distal interphalangeal joint was subsequently performed. A biopsy of sentinel lymph nodes was negative. Due to the result of preoperative positron emission tomography-computed tomography scanning, sweeping of axillary lymph nodes was considered dispensable and was skipped. At the 2-year follow-up, the patient showed a quick recovery and no sign of recurrence. CONCLUSION: Our successful diagnosis and treatment of the case highlights the need for additional attention to long-standing non-healing lesions of the nail bed and the necessity for discreet evaluation and customization of surgical interventions.

19.
Medicine (Baltimore) ; 98(48): e18146, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770253

RESUMO

Left atrial (LA) remodeling has been identified to predict atrial fibrillation (AF) and heart failure. However, the role of LA diameter (LAD) in patients with heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) remains poorly understood.A total of 142 patients including 71 subjects with AF (21 of HFpEF, 22 of HFmrEF, and 28 of HFrEF) and 71 ejection fraction (EF)-matched subjects with sinus rhythm (SR) were included in the study. Baseline characteristics and echocardiographic parameters including LAD were compared between both groups as well as among HFpEF, HFmrEF, and HFrEF.In receiver-operating characteristic (ROC) analyses, LAD predicted AF in HFpEF, HFmrEF, and HFrEF [area under the curve (AUC): 0.646; P = .03]. LAD was negatively association with left ventricular ejection fraction while positively with Nt-proNP and left ventricular end-diastolic diameter (regression coefficient: -0.239, P = .004; regression coefficient: 0.191, P = .023; regression coefficient: 0.357, P < .001). In ROC analyses, LAD predicted HFrEF among the 3 categories (AUC: 0.629, P = .01).In the setting of HF, LAD was higher in AF than in and SR, and predicted AF. Furthermore, LAD was associated with severity of HF in HFpEF, HFmrEF, and HFrEF, and also predicted HFrEF.


Assuntos
Átrios do Coração , Insuficiência Cardíaca , Volume Sistólico , Disfunção Ventricular Esquerda , Função Ventricular Esquerda/fisiologia , Idoso , Idoso de 80 Anos ou mais , China , Ecocardiografia/métodos , Ecocardiografia/estatística & dados numéricos , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Tamanho do Órgão , Prognóstico , Estudos Retrospectivos , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
20.
Int J Pharm ; 572: 118797, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678383

RESUMO

Wet granulation of powders is a key unit operation in the pharmaceutical industry. Due to the complexity of the granulation process taking place in a short time, observing and measuring the granulation process is challenging with conventional experimental methods. In this study, synchrotron-based X-ray imaging techniques were, for the first time, employed to capture the dynamic granulation process with a single drop impacting method in pharmaceutical powder beds. Five common pharmaceutical excipients, two active pharmaceutical ingredients (APIs) and their mixtures were used as the powder beds. The dynamic interaction between the liquid binder and solid powders were observed from high resolution X-ray images captured. Results show that pharmaceutical powder properties, including particle size, hydrophilicity, and morphology, have significant influence on the dynamic granulation process and the final granular product.

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