Publications by authors named "Qun Yu"

101 Publications

Understanding the combined effect and inhibition mechanism of 4-hydroxycinnamic acid and ferulic acid as tyrosinase inhibitors.

Authors:
Qun Yu Liuping Fan

Food Chem 2021 Aug 24;352:129369. Epub 2021 Feb 24.

State Key Laboratory of Food Science & Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, China; Collaborat Innovat Ctr Food Safety & Qual Control, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, China. Electronic address:

The development of tyrosinase inhibitors to prevent the enzymatic browning have become a research hotspot in food industry. 4-Hydroxycinnamic acid (CA) and ferulic acid (FA) are both the derivates of cinnamic acids, which are widely coexisted in plants seeds and leaves. CA combined with FA (inhibition rate of 90.44%) were found to effectively inhibit tyrosinase activity than employing CA and FA alone (inhibition rate of 12.15% and 22.17%, respectively). CA-FA-tyrosinase complex resulted in fluorescence quenching. The first-order kinetics and Weibull models well described the inactivation of tyrosinase at 2-4 mM and 6-10 mM of CA and FA, respectively. Additionally, UV-vis spectrum indicated that several characteristic groups such as hydroxyl group in CA competed with the nucleophilic attack of intramolecular cyclization, leading to the decrease of characteristic peak. Molecular docking further studied that CA and FA interacted with the activity cavity of tyrosinase by amino acids residues Ser282, His263, and Val283.
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http://dx.doi.org/10.1016/j.foodchem.2021.129369DOI Listing
August 2021

Intermittent Hypoxia Exposure Can Prevent Reductions in Hemoglobin Concentration After Intense Exercise Training in Rats.

Front Physiol 2021 19;12:627708. Epub 2021 Feb 19.

Department of Exercise Biochemistry, College of Exercise and Health, Guangzhou Sport University, Guangzhou, China.

Intense exercise training can induce low concentrations of hemoglobin, which may be followed by maladaptation. Therefore, it is important for athletes to prevent low concentrations of hemoglobin during intense exercise training. In this study, we explored whether different protocols of intermittent hypoxic exposure (IHE, normobaric hypoxia, 14.5% O) could prevent the exercise training-induced reduction in hemoglobin concentration in rats. Six-week-old male Sprague-Dawley rats were subjected to progressive intense treadmill exercise training over three weeks followed by three weeks of training with IHE after exercise. IHE lasted either 1 h, 2 h, or 1 h + 1 h (separated by a 3-h interval) after the exercise sessions. Hematological parameters, including hemoglobin concentration [(Hb)], red blood cells (RBCs), and hematocrit (Hct), and both renal and serum erythropoietin (EPO) were examined. We found that intense exercise training significantly reduced [Hb], RBCs, Hct, food intake and body weight ( < 0.01). Analysis of reticulocyte hemoglobin content (CHr) and reticulocyte counts in the serum of the rats suggested that this reduction was not due to iron deficiency or other cofounding factors. The addition of IHE after the intense exercise training sessions significantly alleviated the reduction in [Hb], RBCs, and Hct ( < 0.05) without an obvious impact on either food intake or body weight ( > 0.05). Increase in reticulocyte count in the rats from the IHE groups ( < 0.05 or < 0.01) suggests that IHE promotes erythropoiesis to increase the hemoglobin concentration. Furthermore, the addition of IHE after the intense exercise training sessions also significantly increased the concentration of renal EPO ( < 0.05), although the increase of the serum EPO level was statistically insignificant ( > 0.05). The different IHE protocols were similarly effective at increasing renal EPO and preventing the training-induced decreases in [Hb], RBCs, and Hct. Collectively, this study suggests that IHE may be used as a new strategy to prevent intense exercise training-induced reductions in [Hb], and deserves future exploration in athletes.
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http://dx.doi.org/10.3389/fphys.2021.627708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935520PMC
February 2021

Silica Capsules Templated from Metal-Organic Frameworks for Enzyme Immobilization and Catalysis.

Langmuir 2021 03 2;37(10):3166-3172. Epub 2021 Mar 2.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.

Inspired by the unique biological microenvironments of eukaryotic cells, hollow capsules are promising to immobilize enzymes due to their advantages for physical protection and improved activity of enzymes. Herein, we report a facile method to fabricate silica (SiO) capsules using zeolitic imidazole framework-8 nanoparticles (ZIF-8 NPs) as templates for enzyme immobilization and catalysis. Enzyme-encapsulated SiO capsules are obtained by encapsulation of enzymes in ZIF-8 NPs and subsequent coating of silica layers, followed by the removal of templates in a mild condition (i.e., ethylenediaminetetraacetic acid (EDTA) solution). The enzyme (i.e., horseradish peroxidase, HRP) activity in SiO capsules is improved more than 15 times compared to that of enzyme-loaded ZIF-8 NPs. Enzymes in SiO capsules maintain a high relative activity after being subjected to high temperature, enzymolysis, and recycling compared to free enzymes. In addition, multienzymes (e.g., glucose oxidase and HRP) can also be coencapsulated within SiO capsules to show a reaction with a high cascade catalytic efficacy. This work provides a versatile strategy for enzyme immobilization and protection with potential applications in biocatalysis.
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http://dx.doi.org/10.1021/acs.langmuir.1c00065DOI Listing
March 2021

Role of SIK1 in the transition of acute kidney injury into chronic kidney disease.

J Transl Med 2021 02 15;19(1):69. Epub 2021 Feb 15.

Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China.

Background: Acute kidney injury (AKI), with a high morbidity and mortality, is recognized as a risk factor for chronic kidney disease (CKD). AKI-CKD transition has been regarded as one of the most pressing unmet needs in renal diseases. Recently, studies have showed that salt inducible kinase 1 (SIK1) plays a role in epithelial-mesenchymal transition (EMT) and inflammation, which are the hallmarks of AKI-CKD transition. However, whether SIK1 is involved in AKI-CKD transition and by what mechanism it regulates AKI-CKD transition remains unknown.

Methods: We firstly detected the expression of SIK1 in kidney tissues of AKI patients and AKI mice by immunohistochemistry staining, and then we established Aristolochic acid (AA)-induced AKI-CKD transition model in C57BL/6 mice and HK2 cells. Subsequently, we performed immunohistochemistry staining, ELISA, real-time PCR, Western blot, immunofluorescence staining and Transwell assay to explore the role and underlying mechanism of SIK1 on AKI-CKD transition.

Results: The expression of SIK1 was down-regulated in AKI patients, AKI mice, AA-induced AKI-CKD transition mice, and HK2 cells. Functional analysis revealed that overexpression of SIK1 alleviated AA-induced AKI-CKD transition and HK2 cells injury in vivo and in vitro. Mechanistically, we demonstrated that SIK1 mediated AA-induced AKI-CKD transition by regulating WNT/β-catenin signaling, the canonical pathway involved in EMT, inflammation and renal fibrosis. In addition, we discovered that inhibition of WNT/β-catenin pathway and its downstream transcription factor Twist1 ameliorated HK2 cells injury, delaying the progression of AKI-CKD transition.

Conclusions: Our study demonstrated, for the first time, a protective role of SIK1 in AKI-CKD transition by regulating WNT/β-catenin signaling pathway and its downstream transcription factor Twist1, which will provide novel insights into the prevention and treatment AKI-CKD transition in the future.
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http://dx.doi.org/10.1186/s12967-021-02717-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885408PMC
February 2021

AD Resemblance Atrophy Index as a Diagnostic Biomarker for Alzheimer's Disease: A Retrospective Clinical and Biological Validation.

J Alzheimers Dis 2021 ;79(3):1023-1032

Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Magnetic resonance imaging (MRI) provides objective information about brain structural atrophy in patients with Alzheimer's disease (AD). This multi-structural atrophic information, when integrated as a single differential index, has the potential to further elevate the accuracy of AD identification from normal control (NC) compared to the conventional structure volumetric index.

Objective: We herein investigated the performance of such an MRI-derived AD index, AD-Resemblance Atrophy Index (AD-RAI), as a neuroimaging biomarker in clinical scenario.

Method: Fifty AD patients (19 with the Amyloid, Tau, Neurodegeneration (ATN) results assessed in cerebrospinal fluid) and 50 age- and gender-matched NC (19 with ATN results assessed using positron emission tomography) were recruited in this study. MRI-based imaging biomarkers, i.e., AD-RAI, were quantified using AccuBrain®. The accuracy, sensitivity, specificity, and area under the ROC curve (AUC) of these MRI-based imaging biomarkers were evaluated with the diagnosis result according to clinical criteria for all subjects and ATN biological markers for the subgroup.

Results: In the whole groups of AD and NC subjects, the accuracy of AD-RAI was 91%, sensitivity and specificity were 88% and 96%, respectively, and the AUC was 92%. In the subgroup of 19 AD and 19 NC with ATN results, AD-RAI results matched completely with ATN classification. AD-RAI outperforms the volume of any single brain structure measured.

Conclusion: The finding supports the hypothesis that MRI-derived composite AD-RAI is a more accurate imaging biomarker than individual brain structure volumetry in the identification of AD from NC in the clinical scenario.
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http://dx.doi.org/10.3233/JAD-201033DOI Listing
January 2021

An MRI-based strategy for differentiation of frontotemporal dementia and Alzheimer's disease.

Alzheimers Res Ther 2021 01 12;13(1):23. Epub 2021 Jan 12.

Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, Guangdong, China.

Background: The differential diagnosis of frontotemporal dementia (FTD) and Alzheimer's disease (AD) is difficult due to the overlaps of clinical symptoms. Structural magnetic resonance imaging (sMRI) presents distinct brain atrophy and potentially helps in their differentiation. In this study, we aim at deriving a novel integrated index by leveraging the volumetric measures in brain regions with significant difference between AD and FTD and developing an MRI-based strategy for the differentiation of FTD and AD.

Methods: In this study, the data were acquired from three different databases, including 47 subjects with FTD, 47 subjects with AD, and 47 normal controls in the NACC database; 50 subjects with AD in the ADNI database; and 50 subjects with FTD in the FTLDNI database. The MR images of all subjects were automatically segmented, and the brain atrophy, including the AD resemblance atrophy index (AD-RAI), was quantified using AccuBrain®. A novel MRI index, named the frontotemporal dementia index (FTDI), was derived as the ratio between the weighted sum of the volumetric indexes in "FTD dominant" structures over that obtained from "AD dominant" structures. The weights and the identification of "FTD/AD dominant" structures were acquired from the statistical analysis of NACC data. The differentiation performance of FTDI was validated using independent data from ADNI and FTLDNI databases.

Results: AD-RAI is a proven imaging biomarker to identify AD and FTD from NC with significantly higher values (p < 0.001 and AUC = 0.88) as we reported before, while no significant difference was found between AD and FTD (p = 0.647). FTDI showed excellent accuracy in identifying FTD from AD (AUC = 0.90; SEN = 89%, SPE = 75% with threshold value = 1.08). The validation using independent data from ADNI and FTLDNI datasets also confirmed the efficacy of FTDI (AUC = 0.93; SEN = 96%, SPE = 70% with threshold value = 1.08).

Conclusions: Brain atrophy in AD, FTD, and normal elderly shows distinct patterns. In addition to AD-RAI that is designed to detect abnormal brain atrophy in dementia, a novel index specific to FTD is proposed and validated. By combining AD-RAI and FTDI, an MRI-based decision strategy was further proposed as a promising solution for the differential diagnosis of AD and FTD in clinical practice.
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http://dx.doi.org/10.1186/s13195-020-00757-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805212PMC
January 2021

Scoring system for poor limb perfusion after limb fracture in children.

World J Clin Cases 2020 Dec;8(23):5926-5934

Department of Pediatric Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.

Background: Assessment of the vascular status following limb fracture in children is important to evaluate the risk of compartment syndrome, which is an emergency condition.

Aim: To establish a simple and efficient grading scale of limb perfusion in children undergoing surgery for limb fracture.

Methods: This retrospective study included pediatric patients with a limb fracture and postoperative plaster fixation who were admitted at The Department of Pediatric Orthopedics of Xinhua Hospital between February 2017 and August 2017. The outcome was poor limb perfusion, which is defined as the postoperative use of mannitol. The children were divided into two groups: The normal perfusion group and the poor perfusion group. Key risk factors have been selected by univariable analyses to establish the Grading Scale for Vascular Status.

Results: A total of 161 patients were included in the study: 85 in the normal perfusion group and 76 in the poor perfusion group. There were no significant differences in age, sex, body mass index, ethnicity, cause of fracture, fixation, or site of fracture between the two groups. After surgery, the skin temperature ( = 0.048) and skin color ( < 0.001) of the affected limb were significantly different between the two groups. The relative risk and 95% confidence interval for skin temperature of the affected limb, skin color, and range of motion of the affected limb are 2.18 (1.84-2.59), 2.89 (2.28-3.66), and 2.16 (1.83-2.56), respectively. The grading scale was established based on those three factors (score range: 0-3 points). Forty-one patients (32.5%) with score 0 had poor limb perfusion; all patients with scores 1 ( = 32) and 2 ( = 3) had poor limb perfusion (both 100%).

Conclusion: In children undergoing surgery for limb fracture, a higher Grading Scale for Vascular Status score is associated with a higher occurrence of poor limb perfusion. A prospective study is required for validation.
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http://dx.doi.org/10.12998/wjcc.v8.i23.5926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723717PMC
December 2020

HIF‑3α affects preeclampsia development by regulating EVT growth via activation of the Flt‑1/JAK/STAT signaling pathway in hypoxia.

Mol Med Rep 2021 Jan 20;23(1). Epub 2020 Nov 20.

Department of General Surgery and Pediatric Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.

Preeclampsia (PE) is a common obstetric disease occurring after 20 weeks of gestation. Hypoxia‑inducible factor (HIF)‑3α potentially functions as a regulatory factor in PE development, however its specific molecular mechanism remains to be elucidated. The present study aimed to investigate the function of HIF‑3α in trophoblast cell line HTR‑8/SVneo, to provide a better understanding of the pathology and treatment of PE. Normal and PE placentas were obtained from pregnant women. HTR8/SVneo cells were cultured under the condition of normoxia or hypoxia, pretreated with or without AG490, then transfected with HIF‑3α. The gene expression levels of HIF‑3α and Fms like tyrosine kinase receptor (Flt) 1 extracted from the placentas and cells were detected by reverse transcription‑quantitative PCR, and the expression levels of proteins and Janus kinase signal transducer and activator of transcription (JAK/STAT) phosphorylation were detected by western blot analysis. Viability and apoptosis of the treated cells were assessed by MTT and flow cytometry. The results demonstrated that HIF‑3α and Flt‑1 gene expression levels of PE placentas were reduced compared with normal placentas. Under a hypoxic environment, the expression levels of HIF‑3α and Flt‑1, the phosphorylation of JAK/STAT and the cell viability of HTR8/SVneo cells were increased at first and then reduced, whereas cell apoptosis was promoted over time. Under chronic hypoxia, the expression levels of HIF‑3α and Flt‑1, JAK/STAT pathway phosphorylation and cell viability of AG490‑treated HTR8/SVneo cells were reduced, but cell apoptosis was promoted. However, the upregulation of HIF‑3α in HTR8/SVneo cells markedly reversed the effects of AG490 on the cells under hypoxia. Thus, the present study preliminarily demonstrated that HIF‑3α was involved in PE development by regulating extravillous cytotrophoblast growth via Flt‑1 and the JAK/STAT signaling pathway.
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http://dx.doi.org/10.3892/mmr.2020.11701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716387PMC
January 2021

Podocyte-derived extracellular vesicles mediate renal proximal tubule cells dedifferentiation via microRNA-221 in diabetic nephropathy.

Mol Cell Endocrinol 2020 12 12;518:111034. Epub 2020 Sep 12.

Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China; Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China. Electronic address:

Podocyte injury is a key event in the initiation of Diabetic nephropathy (DN). Tubulointerstitium, especially the proximal tubule has been regarded as a target of injury. In the present study, we showed that podocytes induced dedifferentiation of proximal tubular epithelial cells(PTECs) in high-glucose conditions and extracellular vesicles (EVs) mediates the interaction. Then we extracted and identified these EVs derived from podocytes as exosome, further, the EVs induced PTECs dedifferentiation. Total microRNA(miRNA) expression of podocyte-derived EVs was extracted and miR-221 expression was remarkably increased. By making use of the miRNA gain- and loss-of-function approaches, we observed that miR-221 mediated PTECs dedifferentiation. In addition, a dual-luciferase reporter assay confirmed that miR-221 direct target DKK2, which was an inhibitor of Wnt signaling, and overexpression of miR-221 significantly resulted in β-catenin nuclear accumulation. Moreover, we regulated the expression of β-catenin and demonstrated that miR-221 in EVs mediated proximal tubule cells injury through Wnt/β-catenin signaling. Furthermore, inhibition of miR-221 in diabetic mice reversed the abnormal expression of PTECs dedifferentiation related protein. These findings provide unique insights in the mechanisms of proximal tubule cell injury in diabetic nephropathy.
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http://dx.doi.org/10.1016/j.mce.2020.111034DOI Listing
December 2020

Poly(ethylene glycol)-mediated mineralization of metal-organic frameworks.

Chem Commun (Camb) 2020 Sep;56(75):11078-11081

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China. and State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.

We report a one-pot approach for the scalable synthesis of zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) using poly(ethylene glycol) as the mineralizer, where drugs and proteins can be encapsulated in the ZIF-8 NPs for intracellular delivery. The ZIF-8 NPs exhibit high colloidal dispersity and stability (above two weeks) in cell medium.
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http://dx.doi.org/10.1039/d0cc03734fDOI Listing
September 2020

Insights into the Role of Renal Biopsy in Patients with T2DM: A Literature Review of Global Renal Biopsy Results.

Diabetes Ther 2020 Sep 5;11(9):1983-1999. Epub 2020 Aug 5.

Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Introduction: Renal biopsy performed in patients with type 2 diabetes mellitus (T2DM) for atypical or suspected diabetic kidney disease (DKD) reveals one of three possibilities: diabetic nephropathy (DN, pathological diagnosis of DKD), nondiabetic kidney disease (NDKD) and DN plus NDKD (mixed form). NDKD (including the mixed form) is increasingly being recognized worldwide. With the emerging concept of DKD and the complexity of routine application of renal biopsy, the identification of "clinical indicators" to differentiate DKD from NDKD has been an area of active research.

Methods: The PubMed database was searched for relevant articles mainly according to the keyword search method. We reviewed prevalence of the three types of DKD and different pathological lesions of NDKD. We also reviewed the clinical indicators used to identify DKD and NDKD.

Results: The literature search identified 40 studies (5304 data) worldwide between 1977 and 2019 that looked at global renal biopsy and pathological NDKD lesions. The overall prevalence rate of DN, NDKD and DN plus NDKD is reported to be 41.3, 40.6 and 18.1%, respectively. In Asia, Africa (specifically Morocco and Tunisia) and Europe, the most common isolated NDKD pathological type is membranous nephropathy, representing 24.1, 15.1 and 22.6% of cases, respectively. In contrast, focal segmental glomerulosclerosis is reported to be the primary pathological type in North America (specifically the USA) and Oceania (specifically New Zealand), representing 22% and 63.9% of cases, respectively. Tubulointerstitial disease accounts for a high rate in the mixed group (21.7%), with acute interstitial nephritis being the most prevalent (9.3%), followed by acute tubular necrosis (9.0%). Regarding clinical indicators to differentiate DKD from NDKD, a total of 14 indicators were identified included in 42 studies. Among these, the most commonly studied indicators included diabetic retinopathy, duration of diabetes, proteinuria and hematuria. Regrettably, indicators with high sensitivity and specificity have not yet been identified.

Conclusion: To date, renal biopsy is still the gold standard to diagnose diabetes complicated with renal disease, especially when T2DM patients present atypical DKD symptoms (e.g. absence of diabetic retinopathy, shorter duration of diabetes, microscopic hematuria, sub-nephrotic range proteinuria, lower glycated hemoglobin, lower fasting blood glucose). We conclude that renal biopsy as early as possible is of great significance to enable personalized treatment to T2DM patients.
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http://dx.doi.org/10.1007/s13300-020-00888-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434810PMC
September 2020

Manipulating the Click Reactivity of Dibenzoazacyclooctynes: From Azide Click Component to Caged Acylation Reagent by Silver Catalysis.

Angew Chem Int Ed Engl 2020 11 31;59(45):19940-19944. Epub 2020 Aug 31.

CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Center for Biotherapeutics Discovery Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai, 201203, China.

Strain-promoted azide-alkyne cycloaddition using dibenzoazacyclooctyne (DBCO) is widely applied in copper-free bioorthogonal reactions. Reported here is the efficient acid-promoted rearrangement and silver-catalyzed amidation of DBCO, which alters its click reactivity robustly. In the switched click reaction, DBCO, as a caged acylation reagent, enables rapid peptide/protein modification after decaging facilitated by silver catalysts, rendering site-specific conjugation of an IgG antibody by a Fc-targeting peptide.
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http://dx.doi.org/10.1002/anie.202009408DOI Listing
November 2020

Comparative Transcriptomic and Proteomic Analyses Prove that IFN-λ1 is a More Potent Inducer of ISGs than IFN-α against Porcine Epidemic Diarrhea Virus in Porcine Intestinal Epithelial Cells.

J Proteome Res 2020 09 31;19(9):3697-3707. Epub 2020 Jul 31.

Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing 100850, China.

Type III interferon (IFN-λ) is currently considered to be largely nonredundant to type I interferon (IFN-α) in antivirus infection, especially in epithelial cells. Previous studies reported that, compared with IFN-α, IFN-λ exhibited stronger induction of interferon-stimulated genes (ISGs) at the transcriptional level in intestinal epithelial cells and stronger inhibition of porcine epidemic diarrhea virus (PEDV). In this study, the different mechanisms of ISG upregulation induced by IFN-α and IFN-λ1 were compared at the mRNA and protein levels in the porcine intestinal epithelial cell model (IPEC-J2). It was proved that IFN-λ1 consistently exhibited stronger stimulation effects at both levels. At the mRNA level, 132 genes were significantly upregulated upon IFN-λ1 stimulation, while 42 genes upon IFN-α stimulation. At the protein level, 47 proteins were significantly upregulated upon IFN-λ1 stimulation, but only 8 proteins were upregulated upon IFN-α stimulation. The shared upregulated genes/proteins by IFN-λ1 in both transcriptional and translational omics, especially the regulation factors of ISG15, were involved in the JAK-STAT signaling pathway. Compared to IFN-α, IFN-λ1 could induce more consistent upregulation of the key ISGs (ISG15, USP18, OASL, and RSAD2) at 3-24 h postinduction as measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation. It was further confirmed through functional analysis that ISG15 and RSAD2 could inhibit PEDV infection in dose-dependent manners. This study provided solid evidence that IFN-λ1 could induce a more unique and higher ISG expression level, which exhibited anti-PEDV effects on porcine intestinal epithelial cells.
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http://dx.doi.org/10.1021/acs.jproteome.0c00164DOI Listing
September 2020

Leptin promotes endothelial dysfunction in chronic kidney disease by modulating the MTA1-mediated WNT/β-catenin pathway.

Mol Cell Biochem 2020 Oct 6;473(1-2):155-166. Epub 2020 Jul 6.

Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China.

Endothelial dysfunction (ED) has a high incidence in chronic kidney disease (CKD) and is identified as a precursor to cardiovascular events. Recent studies suggest that leptin may be the missing link between ED and CKD. The objective of this study was to investigate the mechanism by which leptin causes ED and the connection with leptin and indicators of ED in CKD patients. Analysis of leptin-treated human umbilical vein endothelial cells (HUVECs) showed increased expression of interleukin 6 (IL-6), endothelin 1 (ET-1) and human monocyte chemoattractant protein 1 (MCP-1), resulting in F-actin recombination and vinculin aggregation as well as endothelial cell migration. In vitro studies have shown that leptin leads to increased WNT1 expression and the accumulation of β-catenin. Metastasis-associated protein 1 (MTA1), a critical upstream modifier of WNT1 signaling, increased the expression level in leptin-mediated regulation. In contrast, opposite results were observed when cells are transfected with MTA1 or WNT1 shRNA lentivirus vectors. Among 160 patients with CKD and 160 healthy subjects, patients with CKD had significantly higher serum leptin levels than those of the control group, which were positively correlated with increased levels of IL-6, ET-1 and MCP-1. However, these levels were negatively correlated with flow-mediated dilatation (FMD). Hence, these investigations provided novel information on the increased serum leptin levels in CKD patients leading to ED via the MTA1-WNT/β-catenin pathway.
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http://dx.doi.org/10.1007/s11010-020-03816-5DOI Listing
October 2020

Hollow Carbon Sphere Nanoreactors Loaded with PdCu Nanoparticles: Void-Confinement Effects in Liquid-Phase Hydrogenations.

Angew Chem Int Ed Engl 2020 Oct 18;59(42):18374-18379. Epub 2020 Aug 18.

Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.

Nanoreactors with hollow structures have attracted great interest in catalysis research due to their void-confinement effects. However, the challenge in unambiguously unraveling these confinement effects is to decouple them from other factors affecting catalysis. Here, we synthesize a pair of hollow carbon sphere (HCS) nanoreactors with presynthesized PdCu nanoparticles encapsulated inside of HCS (PdCu@HCS) and supported outside of HCS (PdCu/HCS), respectively, while keeping other structural features the same. Based on the two comparative nanoreactors, void-confinement effects in liquid-phase hydrogenation are investigated in a two-chamber reactor. It is found that hydrogenations over PdCu@HCS are shape-selective catalysis, can be accelerated (accumulation of reactants), decelerated (mass transfer limitation), and even inhibited (molecular-sieving effect); conversion of the intermediate in the void space can be further promoted. Using this principle, a specific imine is selectively produced. This work provides a proof of concept for fundamental catalytic action of the hollow nanoreactors.
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http://dx.doi.org/10.1002/anie.202007297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590117PMC
October 2020

New insights into antityrosinase capacity and polyphenols of asparagus during hydrothermal treatments.

Authors:
Qun Yu Liuping Fan

Food Chem 2020 Oct 11;326:126968. Epub 2020 May 11.

State Key Laboratory of Food Science & Technology, School of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, China. Electronic address:

An understanding of the antityrosinase capacity and polyphenols changes during hydrothermal treatments was crucial for application of asparagus. Therefore, asparagus extract was treated at a range of 80-160 °C for 30-150 min in a high temperature reactor. The results suggested that tyrosinase inhibition rate of untreated asparagus extract was recorded as 3.26% but significantly increased to 51.22% and 50.80% after heating for 90 min at 140 °C (lnR of 7.21) and 160 °C (lnR of 8.57), respectively. The generation and degradation of polyphenols followed the pseudo-first-order kinetic model. The coumaric acid content was increased from 35.03 μg/mL to 307.66 μg/mL at lnR of 8.16. The degradation of rutin in asparagus extract was far less compared to that of coumaric acid. Compounds formed were determined by UPLC-Q-TOF-MS yielding main fragments at m/z 451 and 601. In conclusion, hydrothermal treatment was a feasible method for increasing the antityrosinase capacity of asparagus.
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http://dx.doi.org/10.1016/j.foodchem.2020.126968DOI Listing
October 2020

Hexanoate-Cucurbit[7]uril: Highly Soluble with Controlled Release Ability.

Chemistry 2020 Aug 20;26(43):9445-9448. Epub 2020 Jul 20.

School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China.

Current drug delivery systems gain more functions with increased complexity. With the idea of less is more, we synthesized hexanoate-cucurbit[7]uril (CB[7]C COONa) with multiple promising features for drug delivery. The hexanoate group integrates multiple functions. It endows CB[7]C COONa extremely high solubility of over 600 mg mL and well-defined pH-controlled release ability without sacrificing on the high binding affinity of CB[7] cavity. Based on the pH-controlled release ability, CB[7]C COONa can be used for controlling the bioactivity of drug molecules. We anticipate that the strategy of function integration would be useful for the design of simple yet powerful drug delivery systems.
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http://dx.doi.org/10.1002/chem.202001959DOI Listing
August 2020

Ultrasound and heating treatments improve the antityrosinase ability of polyphenols.

Food Chem 2020 Jul 14;317:126415. Epub 2020 Feb 14.

State Key Laboratory of Food Science & Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, China.

This paper focused on improving antityrosinase ability of quercetin, cinnamic acid, and ferulic acid (named Q-CA-FA) from Asparagus by combining heating with ultrasound treatments. Fluorescence spectroscopy and UPLC-MS were used to evaluate inhibitory mechanisms. Results showed that the impacts of combining heating (150 °C for 30 min) with ultrasound (600 W for 30 min) treatments were similar to heating treatment (150 °C for 120 min) alone, and the inhibition rate could reach 98.2% in the addition of 5 mM Q-CA-FA. Fluorescence quenching indicated that treated Q-CA-FA-tyrosinase complex was more stable, but combining treatments did not change the major force between tyrosinase and polyphenols. Thermodynamic analysis illustrated that the randomness of compounds was also increased. Interestingly, 2-hydroxy-3-(3-hydroxy-4-methoxy-phenyl)-propionic acid 4-(2,3-dihydroxy-propyl)-phenyl ester was newly detected, which might be the major reason for enhancing antityrosinase ability. Taken together, these results provide a creative insight on increasing antityrosinase activity by combining heating with ultrasound treatments.
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http://dx.doi.org/10.1016/j.foodchem.2020.126415DOI Listing
July 2020

Dual Chalcogen-Chalcogen Bonding Catalysis.

J Am Chem Soc 2020 02 30;142(6):3117-3124. Epub 2020 Jan 30.

School of Chemistry and Chemical Engineering , Shandong University , Jinan 250100 , China.

The noncovalent S···O bonding interaction is an evolutionary force that has been smartly exploited by nature to modulate the conformational preferences of proteins. The employment of this type of weak noncovalent force to drive chemical reactions is promising yet remains largely elusive. Herein, we describe a dual chalcogen-chalcogen bonding catalysis strategy that the distinct chalcogen atoms simultaneously interact with two chalcogen-based electron donors to give rise to the catalytic activity, thus facilitating chemical reactions. Conventional approaches to the Rauhut-Currier-type reactions require the use of strongly nucleophilic Lewis bases as essential promoters. The implementation of this dual chalcogen-chalcogen bonding catalysis strategy allows the simultaneous Se···O bonding interaction between chalcogen-bonding donors and an enone and an alcohol, enabling the realization of the Rauhut-Currier-type reactions in a distinct way. The further implementation of a consecutive dual Se···O bonding catalysis approach enables the achievement of an initial Rauhut-Currier-type reaction to give an enone product which further undergoes an alcohol-addition induced cyclization reaction. This work demonstrates that the nearly linear chalcogen-bonding interaction can differentiate similar alkyl groups to give rise to regioselectivity. Moreover, the new strategy shows its advantage as it not only enables less reactive substrates working efficiently but tolerates inaccessible substrates using conventional methods.
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http://dx.doi.org/10.1021/jacs.9b12610DOI Listing
February 2020

A novel process for asparagus polyphenols utilization by ultrasound assisted adsorption and desorption using resins.

Ultrason Sonochem 2020 May 9;63:104920. Epub 2019 Dec 9.

State Key Laboratory of Food Science & Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, China. Electronic address:

The ultrasound assisted purification of asparagus polyphenols by adsorption and desorption on the macroporous resins was investigated. The ultrasound within the selected intensities (12-120 W) and temperatures (25-35 °C) increased the adsorption and desorption capacities of asparagus polyphenols on D101 resins. Higher ultrasound intensity (120 W) and lower temperature (25 °C) benefited the adsorption process and the adsorption capacity of total polyphenols after ultrasound was 3.95 mg/g, which was 2 times than that obtained after shaking at 120 rpm. Meanwhile, ultrasound can significantly shorten the equilibrium time and the adsorption process of asparagus polyphenols could be well described by Pseudo-second order model and Freundlich model. Stereoscopic microscope was first used to investigate the microstructure characterization of resins, indicating that ultrasound mainly enhanced the surface roughness of resins. Interestingly, rutin possessed the highest adsorption capacities and ferulic acid had the highest the desorption capacities among the studied individual polyphenols. The obtained results evidenced on a progressive insight of application of ultrasound assisted resins for purification of asparagus polyphenols.
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http://dx.doi.org/10.1016/j.ultsonch.2019.104920DOI Listing
May 2020

Antifouling and pH-Responsive Poly(Carboxybetaine)-Based Nanoparticles for Tumor Cell Targeting.

Front Chem 2019 22;7:770. Epub 2019 Nov 22.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, China.

Nanocarriers with responsibility and surface functionality of targeting molecules have been widely used to improve therapeutic efficiency. Hence, we report the assembly of pH-responsive and targeted polymer nanoparticles (NPs) composed of poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) as the core and poly(carboxybetaine methacrylate) (PCBMA) as the shell, functionalized with cyclic peptides containing Arginine-Glycine-Aspartic acid--Phenylalanine-Lysine (RGD). The resulting polymer NPs (PDPA@PCBMA-RGD NPs) can maintain the pH-responsivity of PDPA (pKa ~6.5) and low-fouling property of PCBMA that significantly resist non-specific interactions with RAW 264.7 and HeLa cells. Meanwhile, PDPA@PCBMA-RGD NPs could specifically target αβ integrin-expressed human glioblastoma (U87) cells. The pH-responsiveness and low-fouling properties of PDPA@PCBMA NPs are comparable to PDPA@poly(ethylene glycol) (PDPA@PEG) NPs, which indicates that PCBMA is an alternative to PEG for low-fouling coatings. The advantage of PDPA@PCBMA NPs lies in the presence of carboxyl groups on their surfaces for further modification (e.g., RGD functionalization for cell targeting). The reported polymer NPs represent a new carrier that have the potential for targeted therapeutic delivery.
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http://dx.doi.org/10.3389/fchem.2019.00770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883901PMC
November 2019

Peptidyl-Lys metalloendopeptidase (Lys-N) purified from dry fruit of Grifola frondosa demonstrates "mirror"digestion property with lysyl endopeptidase (Lys-C).

Rapid Commun Mass Spectrom 2020 Jan;34(2):e8573

Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing, 100850, China.

Rationale: Lys-N, also known as lysine-specific metalloendopeptidase, functions as the "sister" enzyme of lysyl endopeptidase (Lys-C) in proteomic research. Its digestion specificity at the N-terminal lysine residue makes it a very useful tool in proteomics analysis, especially in mass spectrometry (MS)-based de novo sequencing of proteins.

Methods: Here we present a complete production process of highly purified Lys-N from dry fruit of Grifola frondosa (maitake mushroom). The purification process includes one step of microfiltration plus one step of UF/DF (ultrafiltration used in tandem with a diafiltration method) recovery and four steps of chromatographic purification.

Results: The overall yield of the process was approximately 6.7 mg Lys-N protein/kg dry fruit of G. frondosa. The assay data demonstrated that the purified Lys-N exhibited high enzymatic activity and specificity.

Conclusions: The novel production process provides for the first time the extraction of Lys-N from dry fruit of G. frondosa. The process is also stable and scalable, and provides an economic way of producing the enzyme in large quantities for MS-based proteomics and other biological studies.
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http://dx.doi.org/10.1002/rcm.8573DOI Listing
January 2020

Advancing Metal-Phenolic Networks for Visual Information Storage.

ACS Appl Mater Interfaces 2019 Aug 31;11(32):29305-29311. Epub 2019 Jul 31.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering , Shandong University , Jinan , Shandong 250100 , China.

We report a facile inking strategy for visual information storage (e.g., writing, printing, and beyond) via surface modification of substrates with polyphenols and subsequent in situ formation of metal-phenolic networks (MPNs) on the substrates. The reported technique has several advantages compared with current printing techniques. Diverse substrates can be used to fulfill the requirements for different applications (e.g., printing, writing, painting, and stamping). A range of colors (e.g., yellow, blue, and green) can be realized using different polyphenols (e.g., tannic acid, gallic acid, and pyrogallol) and metal ions (e.g., Cu, Fe, and Ti). The disadvantages (e.g., ink precipitation, color fading) associated with writing or printing using traditional ink can be overcome. The obtained paintings can be easily removed by acids enabling the recycling of substrates. The reported strategy provides a new avenue for the development of portable, nontoxic, and green technologies for writing, printing, and beyond, which expands the applications of MPN-based materials.
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http://dx.doi.org/10.1021/acsami.9b09830DOI Listing
August 2019

Five individual polyphenols as tyrosinase inhibitors: Inhibitory activity, synergistic effect, action mechanism, and molecular docking.

Food Chem 2019 Nov 27;297:124910. Epub 2019 May 27.

Institute of Food Research, Hezhou University, Guangxi 542899, China.

Polyphenols can inhibit the enzymatic browning in food, but their indistinct synergistic effect and conformational change have limited their applications. In this paper, the mixture of quercetin, cinnamic acid and ferulic acid (Group 11, K = 0.239 mM) possessed a higher inhibition ability than quercetin (K = 0.361 mM), which could promote the spontaneous binding process. The final Group 11-tyrosinase complex is more stable, and the hydrophobic effect is the major driving force during the binding process. Moreover, there is not a direct relationship between the destruction of secondary structures and catalytic activity of tyrosinase. The interaction between ferulic acid and tyrosinase could destroy the secondary structures of enzyme but it had little impact on the tyrosinase activity. Molecular docking suggested that three polyphenols from Group 11 have synergistic effect on tyrosinase. This study provides new perspectives about the development of tyrosinase inhibitors in food products.
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http://dx.doi.org/10.1016/j.foodchem.2019.05.184DOI Listing
November 2019

Polyphenol-Based Particles for Theranostics.

Theranostics 2019 18;9(11):3170-3190. Epub 2019 May 18.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.

Polyphenols, due to their high biocompatibility and wide occurrence in nature, have attracted increasing attention in the engineering of functional materials ranging from films, particles, to bulk hydrogels. Colloidal particles, such as nanogels, hollow capsules, mesoporous particles and core-shell structures, have been fabricated from polyphenols or their derivatives with a series of polymeric or biomolecular compounds through various covalent and non-covalent interactions. These particles can be designed with specific properties or functionalities, including multi-responsiveness, radical scavenging capabilities, and targeting abilities. Moreover, a range of cargos (e.g., imaging agents, anticancer drugs, therapeutic peptides or proteins, and nucleic acid fragments) can be incorporated into these particles. These cargo-loaded carriers have shown their advantages in the diagnosis and treatment of diseases, especially of cancer. In this review, we summarize the assembly of polyphenol-based particles, including polydopamine (PDA) particles, metal-phenolic network (MPN)-based particles, and polymer-phenol particles, and their potential biomedical applications in various diagnostic and therapeutic applications.
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http://dx.doi.org/10.7150/thno.31847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567970PMC
July 2020

Overexpression of TIM-3 in Macrophages Aggravates Pathogenesis of Pulmonary Fibrosis in Mice.

Am J Respir Cell Mol Biol 2019 12;61(6):727-736

Beijing Institute of Transfusion Medicine, Beijing, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disorder and lacks effective treatments because of unclear mechanisms. Aberrant function of alveolar macrophages is directly linked to pulmonary fibrosis. Here, we show TIM-3 (T-cell immunoglobulin domain and mucin domain-3), a key regulator of macrophage function, aggravates pulmonary fibrosis. TIM-3 mRNA of patients with IPF was analyzed based on the Gene Expression Omnibus and Array Express databases. Lung pathology and profibrotic molecules were assessed in a bleomycin (BLM)-induced pulmonary fibrosis model using wild-type (WT) and TIM-3 transgenic (TIM-3-TG) mice. Macrophage cells, RAW264.7, were then applied to investigate the effect of macrophage TIM-3 under BLM exposure . Macrophage depletion and adoptive-transfer experiments were finally performed to examine lung morphology and profibrotic molecules. TIM-3 expression was increased both in patients with IPF and in our BLM-induced mouse model. TIM-3-TG mice developed more serious pathological changes in lung tissue and higher expressions of TGF-β1 (transforming growth factor-β1) and IL-10 than WT mice. After BLM treatment, TGF-β1 and IL-10 expression was significantly decreased in RAW264.7 cells after TIM-3 knock-out, whereas it was increased in TIM-3-TG peritoneal macrophages. The scores of pulmonary fibrosis in WT and TIM-3-TG mice were significantly reduced, and there was no difference between them after macrophage depletion. Furthermore, WT mice receiving adoptive macrophages from TIM-3-TG mice also had more serious lung fibrosis and increased expression of TGF-β1 and IL-10 than those receiving macrophages from WT mice. Our findings revealed that overexpressed TIM-3 in alveolar macrophages aggravated pulmonary fibrosis.
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http://dx.doi.org/10.1165/rcmb.2019-0070OCDOI Listing
December 2019

Use of ultrasound combined with magnetic resonance imaging for diagnosis of breast masses and fibroids.

J Int Med Res 2019 Jul 2;47(7):3070-3078. Epub 2019 Jun 2.

1 Department of Ultrasonography, Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Chinese Medicine, Xuanwu, Nanjing, Jiangsu, China.

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http://dx.doi.org/10.1177/0300060519848611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683940PMC
July 2019

Divalent oseltamivir analogues as potent influenza neuraminidase inhibitors.

Carbohydr Res 2019 May 1;477:32-38. Epub 2019 Apr 1.

Research Centre of Modern Analytical Technology, Tianjin University of Science & Technology, No. 29, 13th Avenue, TEDA, Tianjin, 300457, China; China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, Tianjin, 300457, China. Electronic address:

A panel of divalent oseltamivir and guanidino oseltamivir analogues with esterification on the carboxyl acid group as potent inhibitors of influenza virus neuraminidase was prepared via click reaction. The primary structure activity relationship study demonstrated that appropriate distance between two oseltamivir monomers around 30 Å can crosslink two adjacent neuraminidase tetramers on the virion surface and result in highly effective NA inhibitors against three strains of influenza virus and H7N9 virus like particle. This strategy also provides a basis for the multivalent modification on oseltamivir.
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http://dx.doi.org/10.1016/j.carres.2019.03.012DOI Listing
May 2019

Succinimide-Promoted Malonylamination of Alkenes with Amines and Iodonium Ylides via Trapping of Transient Aminium Radical Cations.

Org Lett 2019 04 3;21(8):2923-2926. Epub 2019 Apr 3.

School of Chemistry and Chemical Engineering, Key Laboratory of the Colloid and Interface Chemistry , Shandong University , Jinan 250100 , China.

A conceptually distinct strategy enabling malonylamination of alkenes with abundant amines and iodonium ylides without assistance of any transition metal was developed. Succinimide was identified as a proton shuttle that can not only largely accelerate the process of trapping highly unstable radical ion pairs with alkenes but also significantly improve the chemical yields.
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http://dx.doi.org/10.1021/acs.orglett.9b00983DOI Listing
April 2019

Peptide Self-Assembly Nanoparticles Loaded with Panobinostat to Activate Latent Human Immunodeficiency Virus.

J Biomed Nanotechnol 2019 May;15(5):979-992

Highly active antiretroviral therapy (HAART) can turn human immunodeficiency virus-1 (HIV-1) infection into a controllable chronic disease, but because of the presence of an HIV reservoir, it cannot completely eliminate the virus in HIV-infected patients. The activation of latent reservoirs is the key to the successful treatment of acquired immune deficiency syndrome (AIDS). As a class of latency-reversing agents (LRAs), histone deacetylase inhibitors (HDACis), such as panobinostat, have been the most widely investigated, but most of them have resulted in only a modest and transient activation of HIV latency. To improve the potency of latency activation, an injectable peptide self-assembly nanoparticle loaded with panobinostat (PNP-P) was designed with the ability to efficiently penetrate the cell to achieve better drug delivery and activation of latent HIV. The results confirmed that these nanoparticles could activate latently infected cells and and activate peripheral blood mononuclear cells (PBMCs) from latently infected patients . Increased cellular drug uptake made the PNP-P more effective than panobinostat alone. Therefore, this strategy demonstrates that nanotechnology can help improve the activation of latent HIV, and this study lays a foundation for further development of LRA delivery systems for use against an HIV reservoir.
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http://dx.doi.org/10.1166/jbn.2019.2764DOI Listing
May 2019