Publications by authors named "Yanping Sun"

112 Publications

Luminescent Covalent Organic Frameworks for Biosensing and Bioimaging Applications.

Small 2021 Oct 3:e2103516. Epub 2021 Oct 3.

Research Center for Biosensor and Nanotheranostic, School of Biomedical Engineering, Health Science Center, Shenzhen University, Guangdong, 518060, P. R. China.

Luminescent covalent organic frameworks (LCOFs) have attracted significant attention due to their tunability of structures and photophysical properties at molecular level. LCOFs are built to highly ordered and periodic 2D or 3D framework structures through covalently assembling with various luminophore building blocks. Recently, the advantages of LCOFs including predesigned properties of structure, unique photoluminescence, hypotoxicity and good biocompatibility and tumor penetration, broaden their applications in biorelated fields, such as biosensing, bioimaging, and drug delivery. A specific review that analyses the advances of LCOFs in the field of biosensing and bioimaging is thus urged to emerge. Here the construction of LCOFs is reviewed first. The synthetic chemistry of LCOFs highlights the key role of chemical linkages, which not only concrete the building blocks but also affect the optical properties and even can act as the responsive sites for potential sensing applications. How to brighten LCOFs are clarified through description of structure managements. The ability to utilize the luminescence of LCOFs for applications in biosensing and bioimaging is discussed using state-of-the-art examples of varied practical goals. A prospect finally addresses opportunities and challenges the development of LCOFs facing from chemistry, physics to the applications, according to their current progress.
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http://dx.doi.org/10.1002/smll.202103516DOI Listing
October 2021

Role of NLRP3 Inflammasome in Lupus Nephritis and Therapeutic Targeting by Phytochemicals.

Front Pharmacol 2021 20;12:621300. Epub 2021 Aug 20.

Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, China.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune inflammatory condition that affects multiple organs and provokes extensive and severe clinical manifestations. Lupus nephritis (LN) is one of the main clinical manifestations of SLE. It refers to the deposition of immune complexes in the glomeruli, which cause kidney inflammation. Although LN seriously affects prognosis and represents a key factor of disability and death in SLE patients, its mechanism remains unclear. The NACHT, leucine-rich repeat (LRR), and pyrin (PYD) domains-containing protein 3 (NLRP3) inflammasome regulates IL-1β and IL-18 secretion and gasdermin D-mediated pyroptosis and plays a key role in innate immunity. There is increasing evidence that aberrant activation of the NLRP3 inflammasome and downstream inflammatory pathways play an important part in the pathogenesis of multiple autoimmune diseases, including LN. This review summarizes research progress on the elucidation of NLRP3 activation, regulation, and recent clinical trials and experimental studies implicating the NLRP3 inflammasome in the pathophysiology of LN. Current treatments fail to provide durable remission and provoke several sides effects, mainly due to their broad immunosuppressive effects. Therefore, the identification of a safe and effective therapeutic approach for LN is of great significance. Phytochemicals are found in many herbs, fruits, and vegetables and are secondary metabolites of plants. Evidence suggests that phytochemicals have broad biological activities and have good prospects in a variety of diseases, including LN. Therefore, this review reports on current research evaluating phytochemicals for targeting NLRP3 inflammasome pathways in LN therapy.
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http://dx.doi.org/10.3389/fphar.2021.621300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417800PMC
August 2021

Interface mechanisms of the catalytic ozonation of humic acids over siliceous ferrihydrite: Morphology, stability, and the catalytic process.

Environ Res 2021 Aug 11;203:111870. Epub 2021 Aug 11.

College of Environment & Resource Sciences, Zhejiang University, Hangzhou, 310058, PR China. Electronic address:

Ferrihydrite (Fh), a precursor of more crystalline Fe (hydr)oxides, exhibits decent catalytic behavior; however, the instability of its amorphous structure limits its engineering applications. Siliceous ferrihydrite (FhSi) was readily synthesized in this study by co-precipitation. The formation of Fe-O-Si linkages did not alter the amorphous state of pure Fh, but increased the surface area (S), reduced the point of zero charge (pH), and prevented the leaching of more iron. X-ray diffraction, Mössbauer and pyridine-Fourier transform infrared (FTIR) spectroscopies, and potentiometric titration revealed the presence of silicon-occupied portions of growth sites on the Fh surface, which increased the coordination symmetry around the Fe atom and inhibited the transition of Fh to more stable crystalline Fe (hydr)oxides during repeated use. Meanwhile, the density of surface hydroxyl groups (Ds) and the total acid content of the catalytic system after five cycles of catalytic ozonation were 56.75 % and 63.58 % higher than those of freshly prepared system, thereby benefiting the catalysis of ozone for generating ·OH. In addition, the lower pH of the FhSi/O system compared to that of the Fh/O system promoted the generation of neutral surface-hydroxyl species on the surface of FhSi, which enabled a decent catalytic performance in alkaline solutions, regardless of the catalytic cycle. Moreover, the removal of humic acids (HA) followed a hydroxy radical reaction, which involved self-decomposition (14.15 %), catalytic ozonation (21.58 %), and peroxone and Fenton-like reactions (64.27 %).
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http://dx.doi.org/10.1016/j.envres.2021.111870DOI Listing
August 2021

Chromatin accessibility landscapes of immune cells in rheumatoid arthritis nominate monocytes in disease pathogenesis.

BMC Biol 2021 04 16;19(1):79. Epub 2021 Apr 16.

Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230021, Anhui, China.

Background: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that involves a variety of cell types. However, how the epigenetic dysregulations of peripheral immune cells contribute to the pathogenesis of RA still remains largely unclear.

Results: Here, we analysed the genome-wide active DNA regulatory elements of four major immune cells, namely monocytes, B cells, CD4 T cells and CD8 T cells, in peripheral blood of RA patients, osteoarthritis (OA) patients and healthy donors using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq). We found a strong RA-associated chromatin dysregulation signature in monocytes, but no other examined cell types. Moreover, we found that serum C-reactive protein (CRP) can induce the RA-associated chromatin dysregulation in monocytes via in vitro experiments. And the extent of this dysregulation was regulated through the transcription factor FRA2.

Conclusions: Together, our study revealed a CRP-induced pathogenic chromatin dysregulation signature in monocytes from RA patients and predicted the responsible signalling pathway as potential therapeutic targets for the disease.
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http://dx.doi.org/10.1186/s12915-021-01011-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050920PMC
April 2021

Uracil-Doped Graphitic Carbon Nitride for Enhanced Photocatalytic Performance.

ACS Appl Mater Interfaces 2021 Mar 3;13(10):12118-12130. Epub 2021 Mar 3.

College of Environment & Resource Sciences, Zhejiang University, Hangzhou 310058, P. R. China.

g-CN is a visible-light photocatalyst with a suitable band gap and good stability. Moreover, g-CN is considered to be earth-abundant, which makes it an appealing photocatalyst. However, due to its small specific surface area, low utilization of visible light, and high photogenerated electron-hole pair recombination rate, the photocatalytic activity of g-CN remains unsatisfactory. In this work, a highly efficient nonmetallic photocatalyst, ., g-CN doped with uracil (denoted U-CN) was successfully developed. Based on the various characterizations and calculations, it is shown that the triazine group in g-CN is replaced with the diazine group in uracil. This occurrence leads to the formation of a new electron-transfer pathway between triazine groups, which can promote the separation of photogenerated electrons and holes. Concurrently, due to the ultrathin structure of the as-prepared U-CN, the material possessed a larger specific surface area than pristine g-CN, which can provide more active sites. Furthermore, the transfer pathway between the electron and hole was also shortened, and the recombination of the electron and hole was inhibited. According to the results, an optimal hydrogen evolution rate of 31.7 mol h g was achieved by U-CN, which is 5.1 times higher as compared to that achieved by pristine g-CN (6.26 mol h g). For the photocatalytic degradation of rhodamine B, the reaction rate constant of U-CN (11.3 × 10 min) is about 5.5 times that of g-CN (2.07 × 10 min). Furthermore, the uracil-doped catalyst was also able to demonstrate good stability after five successive runs.
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http://dx.doi.org/10.1021/acsami.1c00771DOI Listing
March 2021

Does older subjective age predict poorer cognitive function and higher risk of dementia in middle-aged and older adults?

Psychiatry Res 2021 04 15;298:113807. Epub 2021 Feb 15.

Department of Epidemiology and Health Statistics, Public Health College, Qingdao University, Qingdao, China. Electronic address:

As a biopsychosocial marker of aging, subjective age (i.e., the age individuals feel regardless of their actual age) was related to many health issues in the elderly. The purpose of this study is to investigate whether subjective age is associated with subsequent cognition and dementia risk in middle-aged and older adults. Samples were drawn from the English Longitudinal Study of Ageing (ELSA). Participants reported their subjective ages at the baseline (2004/2005), and their cognitive functions were measured after 10 years (2014/2015). Newly diagnosed dementias were recorded between 2006/2007 to 2014/2015. Overall, 6,475 adults aged 50 years or older were included in the current analyses. The relationship between subjective age reported at baseline and cognition assessed ten years later was modeled using multiple linear regression models. Compared to participants who reported a younger subjective age, those who reported an older subjective age were more likely to have poorer cognition after ten years (β = -0.705, P = .002 for memory, β = -1.567, P = .001 for executive function). A Cox proportional hazard regression model suggested that older subjective age was an independent risk factor for incident dementia (HR = 1.737, 95% CI =1.060-2.848). Other than chronological age, subjective age could also be considered as an important predictor for the development of cognitive dysfunction.
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http://dx.doi.org/10.1016/j.psychres.2021.113807DOI Listing
April 2021

Intestinal Flora: A Pivotal Role in Investigation of Traditional Chinese Medicine.

Am J Chin Med 2021 20;49(2):237-268. Epub 2021 Feb 20.

Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin 150040, P. R. China.

Intestinal flora is essential for maintaining host health and plays a unique role in transforming Traditional Chinese Medicine (TCM). TCM, as a bodyguard, has saved countless lives and maintained human health in the long history, especially in this COVID-19 pandemic. Pains of diseases have been removed from the effective TCM therapy, such as TCM preparation, moxibustion, and acupuncture. With the development of life science and technology, the wisdom and foresight of TCM has been more displayed. Furthermore, TCM has been also inherited and developed in innovation to better realize the modernization and globalization. Nowadays, intestinal flora transforming TCM and TCM targeted intestinal flora treating diseases have been important findings in life science. More and more TCM researches showed the significance of intestinal flora. Intestinal flora is also a way to study TCM to elucidate the profound theory of TCM. Processing, compatibility, and properties of TCM are well demonstrated by intestinal flora. Thus, it is no doubt that intestinal flora is a core in TCM study. The interaction between intestinal flora and TCM is so crucial for host health. Therefore, it is necessary to sum up the latest results in time. This paper systematically depicted the profile of TCM and the importance of intestinal flora in host. What is more, we comprehensively summarized and discussed the latest progress of the interplay between TCM and intestinal flora to better reveal the core connotation of TCM.
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http://dx.doi.org/10.1142/S0192415X21500130DOI Listing
March 2021

Daturataturin A, a withanolide in Datura metel L., induces HaCaT autophagy through the PI3K-Akt-mTOR signaling pathway.

Phytother Res 2021 Mar 9;35(3):1546-1558. Epub 2021 Feb 9.

College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China.

Daturataturin A (DTA), a withanolide compound in Datura metel L., exhibits excellent anti-inflammatory and anti-proliferative activities. Here, we report the study of DTA-induced proliferation and inflammation in human immortalized keratinocytes (HaCaTs) and the associated molecular mechanisms. HaCaTs are a model of the epidermal proliferative state of cells. The pharmacodynamics and mechanism of DTA were studied by western blot, immunofluorescence, apoptosis and proliferation detection, and real-time quantitative polymerase chain reaction. We confirmed that DTA induced HaCaT autophagy, which, in turn, induced HaCaT senescence and, ultimately, led to cell cycle arrest. DTA also negatively regulated inflammation through the activation of autophagy. This may be one of the mechanisms underlying the action of Datura metel L. preparation used for the treatment of psoriasis.
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http://dx.doi.org/10.1002/ptr.6921DOI Listing
March 2021

The mediating role of cognition in the relationship between sleep duration and instrumental activities of daily living disability among middle-aged and older Chinese.

Arch Gerontol Geriatr 2021 May-Jun;94:104369. Epub 2021 Feb 1.

Department of Epidemiology and Health Statistics, Public Health College, Qingdao University, Qingdao, China. Electronic address:

Objective: To explore the effect of sleep duration at baseline on the incident IADL disability among middle-aged and older Chinese, and test whether cognition mediates this causality.

Methods: Data were collected from wave 1 (2011-2012) to wave 3 (2015-2016) of the China Health and Retirement Longitudinal Study (CHARLS). Sleep duration was self-reported at baseline. Cognitive function, including episodic memory and mental intactness were measured via a questionnaire. IADL was assessed at baseline and follow-up. Baron and Kenny's causal steps and Karlson/Holm/Breen (KHB) method were conducted to examine the mediating effect.

Results: A total of 10,328 participants free of IADL disability at baseline were included in this study. Over 4 years of follow-up, 17.1% of participants developed IADL disability. Compared to 7-8 h sleep duration, both short sleep (OR=1.460; 95% CI: 1.261-1.690 for sleeping ≤5 h; OR= 1.189; 95% CI: 1.011-1.400 for sleeping 5-7 h) and long sleep (OR=1.703; 95% CI: 1.269-2.286 for sleeping >9 h) were linked with incident IADL disability. KHB method identified significant mediating effect of cognition on the relationship between extreme sleep durations (≤5 h or >9 h) and IADL disability and the proportional mediation through cognition was 21.32% and 21.06% for sleeping ≤5 h and >9 h, respectively.

Conclusion: Both short (sleeping ≤5 h) and long sleep duration (sleeping >9 h) predicted incident IADL disability. Cognition partially mediated the effect of extreme sleep durations on IADL disability.
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http://dx.doi.org/10.1016/j.archger.2021.104369DOI Listing
May 2021

Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects.

Eur J Med Chem 2021 Feb 17;212:113028. Epub 2020 Nov 17.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua RoadShenhe District, Shenyang, 110016, China. Electronic address:

Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a "prodrug". In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation.
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http://dx.doi.org/10.1016/j.ejmech.2020.113028DOI Listing
February 2021

NLRP3 inflammasome upregulates PD-L1 expression and contributes to immune suppression in lymphoma.

Cancer Lett 2021 01 19;497:178-189. Epub 2020 Oct 19.

Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China. Electronic address:

The NLRP3 inflammasome plays a pro-tumorigenic role in various malignancies. However, its potential role in lymphomagenesis remains unclear. In this study, we identified an immunosuppressive state in patients with diffuse large B cell lymphoma (DLBCL), which was characterized by markedly elevated interleukin (IL)-18 levels in lymphoma tissues and positive correlation with programmed death ligand 1 (PD-L1) expression. Furthermore, NLRP3 inflammasome activation in DLBCL cell lines upregulated PD-L1 and reduced the proportion of cytotoxic T cells. NLRP3 inflammasome blockade in vivo suppressed lymphoma growth and ameliorated anti-tumor immunity by downregulating PD-L1 in the tumor microenvironment and decreasing the proportion of PD-1/TIM-3-expressing T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and regulatory T cells. Further in vivo studies revealed IL-18 as the main effector cytokine involved in the negative regulation of anti-lymphoma immunity. Interestingly, NLRP3 blockers combined with anti-PD-L1 treatment exerted antagonistic effects during lymphoma therapy. Altogether, our findings indicate that NLRP3 inflammasome promotes immunosuppression by modulating PD-L1 and immune cells. Accordingly, this study highlights the prognostic and therapeutic values of the NLRP3 inflammasome in lymphoma.
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http://dx.doi.org/10.1016/j.canlet.2020.10.024DOI Listing
January 2021

Traditional uses, phytochemistry and pharmacology of genus Syringa: A comprehensive review.

J Ethnopharmacol 2021 Feb 10;266:113465. Epub 2020 Oct 10.

Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin, 150040, China; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 232 Outer Ring Road, University Town, Guangzhou, 510006, China. Electronic address:

Ethnopharmacological Relevance: Genus Syringa, which belongs to Oleaceae family, contains 21 accepted species mainly distributed in Southeast Europe, Japan, China, Himalayas, etc. The various parts of Syringa species have been used as traditional Chinese herbal medicines for treatment of cough, myocardial ischemia, acute icteric hepatitis, diarrhea, conjunctivitis, bronchitis and other ailments.

Aim Of The Study: A more comprehensive and in-depth review about the phytochemistry, pharmacology, traditional medicinal uses and clinical applications as well as toxicology of Syringa have summarized and hope to provide a relatively novel angle for further clinical applicantion on genus.

Materials And Methods: The literatures about Syringa were collected via a series of scientific search engines including Web of Science, PubMed, Elsevier, Google Scholar, SciFinder and CNKI.

Results: The phytochemical studies revealed that about 302 compounds include phenylpropanoids, iridoids, phenylethanols, flavonoids, triterpenes and other minor compounds have been isolated and identified from Syringa species. Phenylpropanoids and iridoids are the main constituents among these compounds and may be responsible for the activities directly or indirectly. As traditional medicine, Syringa applied to treat cough, diarrhea, acute icteric hepatitis, vomit, abdominal pain, bronchitis and other ailments. Most of traditional uses are related the biological activities and confirmed by modern studies. Pharmacological researches in vitro and in vivo revealed that the extracts and pure compounds possessed significantly hepatoprotective, anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, cardioprotective, immunomodulatory and other activities.

Conclusions: The phytochemistry, pharmacology, traditional uses and clinical applications described in this article demonstrated that Syringa species possessed a huge number of activities and these findings will promote the further action mechanisms studies. However, fewer preclinical and clinical studies are focued on the pharmacokinetics of crudes extracts and conpounds from Syringa. The explored of new agents with Syringa species as ingredients may be limited. It points to the further in-depth investigations on pharmacokinetics as well as toxicological are essential in future for assessment the effectiveness and safety of drug.
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http://dx.doi.org/10.1016/j.jep.2020.113465DOI Listing
February 2021

Ru-Pd Thermoresponsive Nanocatalyst Based on a Poly(ionic liquid) for Highly Efficient and Selectively Catalyzed Suzuki Coupling and Asymmetric Transfer Hydrogenation in the Aqueous Phase.

ACS Appl Mater Interfaces 2020 Sep 15;12(39):44094-44102. Epub 2020 Sep 15.

Henan Key Laboratory of Green Chemistry, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China.

The development of intelligent polymeric materials to precisely control the catalytic sites of heterogeneous catalysts and enable highly efficient catalysis of a cascade reaction is of great significance. Here, the utilization of a polymer ionic liquid (PIL) containing two different anions facilitates the preparation of Ru-Pd catalysts with controllable phase transition temperatures and hydrophilic and hydrophobic surfaces. The combined multifunctionality, synergistic effects, micellar effects, aggregation effects, and temperature responsiveness of the nanocatalyst render it suitable for promoting selectively catalyzed Suzuki coupling and asymmetric transfer hydrogenation in water. Above the lower critical solution temperature (LCST) of the catalyst, it catalyzes only the coupling reaction with a high turnover number (TON) of up to 999.0. Below the LCST, the catalyst catalyzes only the asymmetric transfer hydrogenation with good catalytic activity and enantioselectivity. It is important that the catalyst can be simply and effectively recovered and recycled at least 10 times without significant loss of catalytic activity and enantioselectivity. This study also highlights the superiority of multifunctional heterogeneous catalysts based on PILs, which not only overcome limitations associated with low activity of heterogeneous catalysts but also realize selective reactions according to a temperature change, thereby improving the reactivity and enantioselectivity in multiple organic transformations.
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http://dx.doi.org/10.1021/acsami.0c07811DOI Listing
September 2020

Ru-Pd Thermoresponsive Nanocatalyst Based on a Poly(ionic liquid) for Highly Efficient and Selectively Catalyzed Suzuki Coupling and Asymmetric Transfer Hydrogenation in the Aqueous Phase.

ACS Appl Mater Interfaces 2020 Sep 15;12(39):44094-44102. Epub 2020 Sep 15.

Henan Key Laboratory of Green Chemistry, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China.

The development of intelligent polymeric materials to precisely control the catalytic sites of heterogeneous catalysts and enable highly efficient catalysis of a cascade reaction is of great significance. Here, the utilization of a polymer ionic liquid (PIL) containing two different anions facilitates the preparation of Ru-Pd catalysts with controllable phase transition temperatures and hydrophilic and hydrophobic surfaces. The combined multifunctionality, synergistic effects, micellar effects, aggregation effects, and temperature responsiveness of the nanocatalyst render it suitable for promoting selectively catalyzed Suzuki coupling and asymmetric transfer hydrogenation in water. Above the lower critical solution temperature (LCST) of the catalyst, it catalyzes only the coupling reaction with a high turnover number (TON) of up to 999.0. Below the LCST, the catalyst catalyzes only the asymmetric transfer hydrogenation with good catalytic activity and enantioselectivity. It is important that the catalyst can be simply and effectively recovered and recycled at least 10 times without significant loss of catalytic activity and enantioselectivity. This study also highlights the superiority of multifunctional heterogeneous catalysts based on PILs, which not only overcome limitations associated with low activity of heterogeneous catalysts but also realize selective reactions according to a temperature change, thereby improving the reactivity and enantioselectivity in multiple organic transformations.
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http://dx.doi.org/10.1021/acsami.0c07811DOI Listing
September 2020

Chiral mesoporous silica synthesized by a facile strategy for loading and releasing poorly water-soluble drug.

Drug Dev Ind Pharm 2020 Jul 25;46(7):1177-1184. Epub 2020 Jun 25.

Department of Pharmacy, Hebei University of Science and Technology, Shijiazhuang, China.

Most of the mesoporous chiral mesoporous silica (CMS) was synthesized by the chiral surfactant-directing method. In this study, a facile method was designed to synthesize CMS. In this method, achiral amphiphile was used as templating agents, and dilute ammonia solution was applied to induce the chirality of the CMS. Meanwhile, its morphology can be controlled by changing the concentration of the aqueous ammonia solution. The obtained CMS was characterized by dynamic light scattering (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The results showed that all of the CMS possessed highly ordered mesostructures, and as the concentration of ammonia decreases, the chirality of the CMS becomes more obvious. Water-insoluble drug curcumin (Cur) was used as a model drug. The characteristics of CMS before and after drug loading were further detected by Fourier transform infrared spectrometer (FT-IR), N adsorption-desorption and differential scanning calorimetry (DSC). The result showed that Cur was successfully loaded inside the pores of the CMS and remained an amorphous state due to steric inhibition. Additionally, CMS could significantly increase the release rate of Cur under different pH conditions.
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http://dx.doi.org/10.1080/03639045.2020.1782421DOI Listing
July 2020

Corrigendum to "A systematic comparison of exercise training protocols on animal models of cardiovascular capacity" [Life Sci. 217 (2019) 128-140].

Life Sci 2020 Aug 4;254:117757. Epub 2020 Jun 4.

National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China/CGDB, Shaanxi Normal University College of Life Sciences, Xi'an 710119, China. Electronic address:

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http://dx.doi.org/10.1016/j.lfs.2020.117757DOI Listing
August 2020

Poor lung function accelerates cognitive decline in middle-aged and older adults: Evidence from the English Longitudinal Study of Ageing.

Arch Gerontol Geriatr 2020 Sep - Oct;90:104129. Epub 2020 May 28.

Department of Epidemiology and Health Statistics, Public Health College, Qingdao University, Qingdao, China. Electronic address:

Background/objective: Previous studies have linked lung function to cognitive performance. However, it is not clear whether baseline lung function has an effect on the trajectory of cognitive decline during normal aging. This study aimed to examine the association of baseline lung function with long-term changes in cognition among the middle-aged and older adults.

Methods: Lung function as indicated by forced expiratory volume 1 s (FEV1) and forced vital capacity (FVC), was measured at the baseline examination. Cognition, including memory, time orientation, executive function and processing speed, were tested four times over six years. Generalized estimating equation (GEE) models were used to test the associations between baseline lung function and four visits of cognition in 6080 participants aged 50 years or over from the English Longitudinal Study of Ageing (ELSA).

Results: Compared to participants with higher lung function, those who had lower lung function at baseline experienced a faster rate of decline in memory (joint test: χ = 12.07, df = 3, P = 0.007 for FVC), time orientation (joint test: χ = 9.49, df = 3, P = 0.023 for FVC) and executive function (joint test: χ = 9.13, df = 3, P = 0.028 for FEV1 and joint test: χ = 12.76, df = 3, P = 0.005 for FVC). No association was found between baseline lung function and the rate of decline in processing speed (joint test: χ = 1.29, df = 3, P=0.733 for FEV1 and joint test: χ = 2.35, df = 3, P = 0.503 for FVC).

Conclusions: Poor lung function at baseline predicted a faster rate of cognitive decline in memory, time orientation and executive function. The mechanism for this association deserves further investigation.
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http://dx.doi.org/10.1016/j.archger.2020.104129DOI Listing
December 2020

Spleen and thymus metabolomics strategy to explore the immunoregulatory mechanism of total withanolides from the leaves of Datura metel L. on imiquimod-induced psoriatic skin dermatitis in mice.

Biomed Chromatogr 2020 Sep 5;34(9):e4881. Epub 2020 Jun 5.

Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.

Our previous work demonstrated that total withanolides of Datura metel L. leaves (TWD) exhibited excellent therapeutic effects on psoriasis. However, current knowledge of its mechanisms is incomplete. In this study, integrated spleen and thymus untargeted metabolomics were used to analyze the changes in endogenous metabolites underlying the immunosuppressive activity of TWD on psoriasis animal models induced by imiquimod. The results suggested that TWD treatment markedly attenuated imiquimod-induced psoriasis and showed significant immunosuppressive activity as evidenced by decreased elevation index of spleen and thymus. Meanwhile, TWD significantly reversed the elevation of immunoregulatory factors, including IL-10, IL-17, IL-22 and IL-23. Multivariate trajectory analysis revealed that TWD treatment could restore the psoriasis-disturbed spleen and thymus metabolite profiles towards the normal metabolic status. A total of 25 and 27 metabolites associated with the immunomodulatory effects for which levels changed markedly upon treatment have been identified in spleen and thymus, respectively. These differential metabolites were mainly involved in amino acid metabolism, nucleotide metabolism, fatty acid metabolism and lipid metabolism. Our investigation provided a holistic view of TWD for intervention in psoriasis through immunoregulation and provided further scientific information in vivo about a clinical value of TWD for psoriasis.
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http://dx.doi.org/10.1002/bmc.4881DOI Listing
September 2020

Rational Design of "Three-in-One" Ratiometric Nanoprobes: Protein-Caged Dityrosine, CdS Quantum Dots, and Gold Nanoclusters.

ACS Omega 2020 Apr 9;5(15):8943-8951. Epub 2020 Apr 9.

Beijing Key Laboratory for Bioengineering and Sensing Technology, Research Center for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, P. R. China.

Recently, multiplexed ratiometric fluorescence sensors for detecting several analytes have received much interest because of their multifunctionality. Here, we fabricate a novel trinity fluorescent nanoprobe in which one small-molecule fluorophore, blue-emissive dityrosine (diTyr) residues, and two nanomaterial fluorophores, green-emissive CdS quantum dots (CdSQDs) and red-emissive gold nanoclusters (AuNCs), are cocaged in a bovine serum albumin (BSA) molecule. The large differences of Stokes shifts among diTyr residues, CdSQDs, and AuNCs ensure their emission at a single excitation wavelength. The nanoprobes can be facilely integrated using two-step synthetic reactions. DiTyr residues and AuNCs are formed and bound to the protein cage through the redox reaction between Au and tyrosine residues of BSA, and the CdSQDs are followed to be conjugated to the modified BSA cage-templated CdS combination reaction. With established benign biocompatibility, the nanoprobes can ratiometrically detect intracellular glutathione by significantly enhancing the green emission of the conjugated CdSQDs. Likewise, the ratiometric sensing of solution alkalinity and tris(2-carboxyethyl)phosphine can be achieved using blue-emitted diTyr residues and red-emitted AuNCs as the responsive units, respectively, and the corresponding other two fluorophores as the reference signals. This study addresses a concept of trinity fluorescence ratiometric sensing system with multiple targets and optional references, which should be a promising pathway to meet the challenges from complexing biochemical environments and multivariate analysis.
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http://dx.doi.org/10.1021/acsomega.0c00711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178766PMC
April 2020

Integrated serum metabolomics and network pharmacology approach to reveal the potential mechanisms of withanolides from the leaves of Datura metel L. on psoriasis.

J Pharm Biomed Anal 2020 Jul 3;186:113277. Epub 2020 Apr 3.

Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin, 150040, People's Republic of China. Electronic address:

Psoriasis is a chronic, immune-mediated inflammatory skin disease and highly depends on inflammation and angiogenesis as well as other pathways. Our previous study showed that the withanolides from the leaves of Datura metel L. exhibited significant therapeutically effect on psoriasis, but the mechanisms concerning this effect have not been systematically studied. The purpose of this paper was to investigate the possible mechanism of withanolides for treating psoriasis using an integrated metabolomics and network pharmacology strategy. Untargeted metabolomics profiling of serum with UHPLC/Orbitrap MS and a multivariate data method were performed to discover the potential biomarkers and metabolic pathways. Afterward, the compound-target-pathway network of withanolides for psoriasis was constructed by virtue of network pharmacology. Finally, the crucial pathways were selected by integrating the results of metabolomics and network pharmacology, and then validated by ELISA and western blot analysis. The results showed that withanolides could exert excellent effects on psoriasis through regulating two types of pathways, angiogenesis and inflammation, including sphingolipids metabolism and HIF-1α/VEGF pathway, reflected by inhibiting the production of inflammatory cytokines (IL-1β, IL-6, IL-8, IFN-γ, TNF-α, HIF-1α and VEGF), as well as reducing the protein expressions of HIF-1α and VEGF. Our study successfully explained the polypharmcological mechanisms underlying the efficiency of withanolides from the D. metel L. leaves on treating psoriasis. Meanwhile, it was also valuable for performing a systematical investigation of herb medicines, as well as for efficiently predicting the therapeutic mechanisms of traditional Chinese medicine.
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http://dx.doi.org/10.1016/j.jpba.2020.113277DOI Listing
July 2020

Lipid membranes supported by planar porous substrates.

Chem Phys Lipids 2020 05 22;228:104893. Epub 2020 Feb 22.

Department of Pharmacy, Hebei University of Science and Technology, Shijiazhuang, 050018, China; State Key Laboratory Breeding Base - Hebei Province Key Laboratory of Molecular Chemistry for Drugs, Hebei University of Science and Technology, Shijiazhuang, 050018, China; Hebei Research Center of Pharmaceutical and Chemical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, China. Electronic address:

Biological membranes play key roles in cell life, but their intrinsic complexity motivated the study and development of artificial lipid membranes with the primary aim to reconstitute and understand the natural functions in vitro. Porous-supported lipid membrane (pSLM) has emerged as a flexible platform for studying the surface chemistry of the cell due to their high stability and fluidity, and their ability to study the transmembrane process of the molecules. In this review, the pSLM, for the first time, to our knowledge, was divided into three types according to the way of the porous materials support the lipid membrane, containing the lipid membrane on the pores of the porous materials, the lipid membrane on both sides of the porous materials, the lipid membrane in the pores of the porous materials. All of these pSLMs were systematically elaborated from several aspects, including the substrates, formation, and characterization. Meanwhile, the advantages and disadvantages of each model membranes were summarized. Finally, suggestions for selecting appropriate pSLM and future directions in this area are discussed.
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http://dx.doi.org/10.1016/j.chemphyslip.2020.104893DOI Listing
May 2020

Polyphyllin VII induces apoptotic cell death via inhibition of the PI3K/Akt and NF‑κB pathways in A549 human lung cancer cells.

Mol Med Rep 2020 02 12;21(2):597-606. Epub 2019 Dec 12.

Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, School of Pharmacy, Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China.

Polyphyllin VII is an active compound isolated from Paris polyphylla, which is termed Chonglou in China. The present study was designed to investigate the underlying mechanisms of the antitumor effect of Polyphyllin VII in lung cancer cells. The cytotoxic effect of Polyphyllin VII in human lung cancer A549 cells was analyzed; the results revealed an IC50 value of 0.41±0.10 µM at 24 h. The associated mechanisms were investigated by phase‑contrast microscopy, fluorescence microscopy, flow cytometry and western blot analysis. Exposure of A549 cells to Polyphyllin VII resulted in apoptosis. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF‑κB, and wortmannin, an inhibitor of PI3K, both decreased the proportion of viable A549 cells in the presence of Polyphyllin VII. The ratio of apoptotic cells increased in the presence of wortmannin and PDTC. Western blot analysis revealed that PI3K, phosphorylated (p)‑PI3K, Akt, p‑Akt, NF‑κB and p‑NF‑κB were downregulated following treatment with Polyphyllin VII. Increased caspase‑3 activity, increased poly‑(ADP‑ribose) polymerase cleavage and a downregulation of inhibitor of caspase‑activated DNase were observed following treatment with Polyphyllin VII, and these effects were enhanced by either wortmannin or PDTC. The present results revealed that Polyphyllin VII was able to induce apoptotic cell death in A549 human lung cancer cells via inhibition of the PI3K/Akt and NF‑κB pathways.
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http://dx.doi.org/10.3892/mmr.2019.10879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947863PMC
February 2020

New withanolides with anti-inflammatory activity from the leaves of Datura metel L.

Bioorg Chem 2020 01 28;95:103541. Epub 2019 Dec 28.

Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, People's Republic of China. Electronic address:

Twenty three undescribed withanolides, daturmetelides A-W (1-23), were isolated from 70% EtOH extract of the leaves of Datura metel L. The structural characterizations and relative configurations of 1-23 were elucidated by extensive spectroscopic analysis as well as by comparison with literature values. The absolute configurations of 1 and 3 were determined by X-ray crystallography. Bioassay results showed that 1 and 7 exhibited moderate inhibitory effects against NO production in lipopolysaccharide-stimulated RAW 264.7 cells (IC values of 13.74 μM and 13.92 μM, respectively). In addition, 1 and 7 showed significant anti-inflammatory activities against the production of TNF-α, IL-1β, IL-6 and COX-2. Western blot analysis was further performed to reveal the mechanism of anti-inflammatory action via inhibition of the NF-κB activation.
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http://dx.doi.org/10.1016/j.bioorg.2019.103541DOI Listing
January 2020

Organogels based on amino acid derivatives and their optimization for drug release using response surface methodology.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):266-275

School of Pharmacy, China Medical University, Shenyang, P. R. China.

Organogels are excellent drug carrier for controlled release. Organogels based on amino acid derivatives has been widely used in the area of drug delivery. In this study, a series of the organogel system based on amino acid derivatives gelators was designed and prepared to investigate the structure-property correlation in organogels. To investigate the factors that influence the property of drug release, we varied the formulation in the organogels: gelator structure, gelator concentration, volume of antigelation solvent, and drug loading. Through the Box-Behnken tests, the optimum organogel formulation was obtained. The self-healing properties of the organogel have been utilised for injection of a model lipophilic risperidone , and sustained release of the drug has been studied over about one week . In conclusion, the gelation ability of gelators could be adjusted by the gelator structure. Gel property is related with the whole composition of the formulation. As drug carrier, the drug release property of organogels is affected by multiple factors. Our investigation of the gel release property will play a theoretical guiding role in the application in the drug delivery system.
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http://dx.doi.org/10.1080/21691401.2019.1699833DOI Listing
December 2020

Roles of GluN2C in cerebral ischemia: GluN2C expressed in different cell types plays different role in ischemic damage.

J Neurosci Res 2020 06 10;98(6):1188-1197. Epub 2019 Dec 10.

Department of Pharmacy, Hebei University of Science and Technology, Shijiazhuang, China.

Over the past decade, many studies have focused on clarifying the roles of different N-methyl-d-aspartate (NMDA) receptor subunits in cerebral ischemia, hoping to develop subunit-selective drugs. Recently, more attention was given to studying the role of GluN2C in ischemia damage, which may lead to the development of new NMDA receptor antagonists for cerebral ischemia. Results showed that GluN2C inhibition or knockout can effectively alleviate the ischemic injury caused by middle cerebral artery occlusion and, contrarily, can aggravate the damage to hippocampal CA1 circuit caused by transient global cerebral ischemia. These results indicate the complicated roles of GluN2C in cerebral ischemia. In this minireview, we focus on these findings, describe the roles of GluN2C from different cell origins in ischemic damage, and explain the above inconsistent experimental results.
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http://dx.doi.org/10.1002/jnr.24574DOI Listing
June 2020

Exploring the functions of polymers in adenovirus-mediated gene delivery: Evading immune response and redirecting tropism.

Acta Biomater 2019 10 3;97:93-104. Epub 2019 Aug 3.

Department of Pharmacy, Hebei University of Science and Technology, Shijiazhuang 050018, China; State Key Laboratory Breeding Base - Hebei Province Key Laboratory of Molecular Chemistry for Drugs, Hebei University of Science and Technology, Shijiazhuang 050018, China; Hebei Research Center of Pharmaceutical and Chemical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China. Electronic address:

Adenovirus (Ad) is a promising viral carrier in gene therapy because of its unique attribution. However, clinical applications of Ad vectors are currently restricted by their immunogenicity and broad native tropism. To address these obstacles, a variety of nonimmunogenic polymers are utilized to modify Ad vectors chemically or physically. In this review, we systemically discuss the functions of polymers in Ad-mediated gene delivery from two aspects: evading the host immune responses to Ads and redirecting Ad tropism. With polyethylene glycol (PEG) first in order, a variety of polymers have been developed to shield the surface of Ad vectors and well accomplished to evade the host immune response, block CAR-dependant cellular uptake, and reduce accumulation in the liver. In addition, shielding Ad vectors with targeted polymers (including targeting ligand-conjugated polymers and bio-responsive polymers) can also efficiently retarget Ad vectors to tumor tissues and reduce their distribution in nontargeted tissues. With its potential to evade the immune response and retarget Ad vectors, modification with polymers has been generally regarded as a promising strategy to facilitate the clinical applications of Ad vectors for virotherapy. STATEMENT OF SIGNIFICANCE: There is no doubt that Adenovirus (Ads) are attractive vectors for gene therapy, with high sophistication and effectiveness in overcoming both extra- and intracellular barriers, which cannot be exceeded by any other nonviral gene vectors. Unfortunately, their clinical applications are still restricted by some critical hurdles, including immunogenicity and native broad tropism. Therefore, a variety of elegant strategies have been developed from various angles to address these hurdles. Among these various strategies, coating Ads with nonimmunogenic polymers has attracted much attention. In this review, we systemically discuss the functions of polymers in Ad-mediated gene delivery from two aspects: evading the host immune responses to Ads and redirecting Ad tropism. In addition, the key factors in Ad modification with polymers have been highlighted and summarized to provide guiding theory for the design of more effective and safer polymer-Ad hybrid gene vectors.
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http://dx.doi.org/10.1016/j.actbio.2019.06.059DOI Listing
October 2019

Alcohol Consumption and Functional Limitations in Older Men: Does Muscle Strength Mediate Them?

J Am Geriatr Soc 2019 11 2;67(11):2331-2337. Epub 2019 Aug 2.

Department of Epidemiology and Health Statistics, Public Health College, Qingdao University, Qingdao, China.

Objectives: To evaluate the dose-response relationships between alcohol consumption and functional limitations in older European men, and explore the role of muscle strength as a mediator of these relationships.

Design: Cross-sectional study of older men participating in the Survey of Health, Aging and Retirement in Europe (SHARE).

Setting: Urban and rural households in 17 European countries and Israel.

Participants: A total of 17 870 men aged 65 years and older from the SHARE (Wave 6, 2015) were included in this study.

Measurements: Outcome variables were functional limitations: mobility limitation, arm function limitation, and fine motor limitation. Main exposure variable was alcohol consumption. Mediating factor was grip strength. Basic demographics, life habits, and health status were considered as potential confounders. Dose-response analyses with restricted cubic splines and the Karlson/Holm/Breen method were conducted.

Results: A total of 17 870 participants were included in this study. Dose-response analyses revealed that moderate alcohol consumption was related to the lower odds of reporting mobility limitation (≤35 units/wk) and arm function limitation (≤41 units/wk), with a minimum odds ratio (OR) occurring at 10 units/week drinks for mobility limitation (OR = .71; 95% confidence interval [CI] = .62-.81) and arm function limitation (OR = .66; 95% CI = .59-.75). The odds of reporting the fine motor limitation monotonically increased with alcohol consumption when alcohol consumption was beyond 15 units/week. No significant mediating effect of grip strength on the relationships between alcohol consumption and mobility limitation and arm function limitation was found.

Conclusion: Moderate alcohol consumption has a protective role in mobility and arm function limitation in older European men. Grip strength is not the main mediator of these associations, suggesting that the protective effect is independent of muscle strength. Alcohol consumption is associated with higher odds of reporting fine motor limitation in older European men. J Am Geriatr Soc 67:2331-2337, 2019.
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http://dx.doi.org/10.1111/jgs.16082DOI Listing
November 2019

Reproducibility and Changes in Vena Caval Blood Flow by Using 4D Flow MRI in Pulmonary Emphysema and Chronic Obstructive Pulmonary Disease (COPD): The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Substudy.

Radiology 2019 09 23;292(3):585-594. Epub 2019 Jul 23.

From the Department of Radiology, Feinberg School of Medicine, Northwestern University, 737 N Michigan Ave, Suite 1600, Chicago, IL 60611 (O.R., M.M., H.B., C.B., K.S., J.C.); Departments of Radiology (O.R., S.D., M.R.P., Y.S.), Medicine (P.B., Y.S., R.G.B.), and Epidemiology (R.G.B.), Columbia University Medical Center, New York, NY; Department of Radiology, NewYork-Presbyterian Hospital, New York, NY (O.R.); Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, Ill (M.M.); Departments of Medical Physics (O.W.) and Radiology (D.A.B.), University of Wisconsin School of Medicine and Public Health, Madison, Wis; Division of Cardiology, Johns Hopkins University, Baltimore, Md (J.L., E.M., B.A.V.); Department of Radiology, Biomedical Engineering and Medicine, University of Iowa, Iowa City, Iowa (E.A.H.); and Departments of Radiology (A.S.G.) and Medicine (K.W.), University of California Los Angeles, Los Angeles, Calif.

BackgroundChronic obstructive pulmonary disease (COPD) is associated with hemodynamic changes in the pulmonary vasculature. However, cardiac effects are not fully understood and vary by phenotype of chronic lower respiratory disease.PurposeTo use four-dimensional (4D) flow MRI for comprehensive assessment of the right-sided cardiovascular system, assess its interrater and intraobserver reproducibility, and examine associations with venous return to the right heart in individuals with chronic COPD and emphysema.Materials and MethodsThe Multi-Ethnic Study of Atherosclerosis COPD substudy prospectively recruited participants who smoked and who had COPD and nested control participants from population-based samples. Electrocardiography and respiratory gated 4D flow 1.5-T MRI was performed at three sites with full volumetric coverage of the thoracic vessels in 2014-2017 with postbronchodilator spirometry and inspiratory chest CT to quantify percent emphysema. Net flow, peak velocity, retrograde flow, and retrograde fraction were measured on 14 analysis planes. Interrater reproducibility was assessed by two independent observers, and the principle of conservation of mass was employed to evaluate the internal consistency of flow measures. Partial correlation coefficients were adjusted for age, sex, race/ethnicity, height, weight, and smoking status.ResultsAmong 70 participants (29 participants with COPD [mean age, 73.5 years ± 8.1 {standard deviation}; 20 men] and 41 control participants [mean age, 71.0 years ± 6.1; 22 men]), the interrater reproducibility of the 4D flow MRI measures was good to excellent (intraclass correlation coefficient range, 0.73-0.98), as was the internal consistency. There were no statistically significant differences in venous flow parameters according to COPD severity ( > .05). Greater percent emphysema at CT was associated with greater regurgitant flow in the superior and inferior caval veins and tricuspid valve (adjusted = 0.28-0.55; all < .01), particularly in the superior vena cava.ConclusionFour-dimensional flow MRI had good-to-excellent observer variability and flow consistency. Percent emphysema at CT was associated with statistically significant differences in retrograde flow, greatest in the superior vena cava.© RSNA, 2019See also the editorial by Choe in this issue.
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http://dx.doi.org/10.1148/radiol.2019182143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736177PMC
September 2019

Withanolides, Extracted from Datura Metel L. Inhibit Keratinocyte Proliferation and Imiquimod-Induced Psoriasis-Like Dermatitis via the STAT3/P38/ERK1/2 Pathway.

Molecules 2019 Jul 17;24(14). Epub 2019 Jul 17.

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin 150040, China.

Psoriasis is an immune-mediated inflammatory dermatosis characterized by epidermal hyperplasia and excessive infiltration of inflammatory cells. Withanolides, extracted from L.; are the main effective components for the treatment of psoriasis. However, the precise mechanisms of action of withanolides for the treatment of psoriasis remain unclear. We found that treatment with withanolides alleviated imiquimod (IMQ)-induced epidermal hyperplasia and inflammatory cell infiltration in the effective skin of model mice. In addition, we also found that withanolides suppressed the activation of STAT3, ERK1/2 and P38 signaling pathways in IMQ-stimulated HaCat cells. These results suggest that withanolides possess an anti-inflammatory effect and have significant therapeutic potential for the prevention and treatment of psoriasis.
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http://dx.doi.org/10.3390/molecules24142596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680890PMC
July 2019

Deep semantic lung segmentation for tracking potential pulmonary perfusion biomarkers in chronic obstructive pulmonary disease (COPD): The multi-ethnic study of atherosclerosis COPD study.

J Magn Reson Imaging 2020 02 5;51(2):571-579. Epub 2019 Jul 5.

Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.

Background: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality. Identification of imaging biomarkers for phenotyping is necessary for future treatment and therapy monitoring. However, translation of visual analytic pipelines into clinics or their use in large-scale studies is significantly slowed by time-consuming postprocessing steps.

Purpose: To implement an automated tool chain for regional quantification of pulmonary microvascular blood flow in order to reduce analysis time and user variability.

Study Type: Prospective.

Population: In all, 90 MRI scans of 63 patients, of which 31 had a COPD with a mean Global Initiative for Chronic Obstructive Lung Disease status of 1.9 ± 0.64 (μ ± σ).

Field Strength/sequence: 1.5T dynamic gadolinium-enhanced MRI measurement using 4D dynamic contrast material-enhanced (DCE) time-resolved angiography acquired in a single breath-hold in inspiration. [Correction added on August 20, 2019, after first online publication: The field strength in the preceding sentence was corrected.] ASSESSMENT: We built a 3D convolutional neural network for semantic segmentation using 29 manually segmented perfusion maps. All five lobes of the lung are denoted, including the middle lobe. Evaluation was performed on 61 independent cases from two sites of the Multi-Ethnic Study of Arteriosclerosis (MESA)-COPD study. We publish our implementation of a model-free deconvolution filter according to Sourbron et al for 4D DCE MRI scans as open source.

Statistical Test: Cross-validation 29/61 (# training / # testing), intraclass correlation coefficient (ICC), Spearman ρ, Pearson r, Sørensen-Dice coefficient, and overlap.

Results: Segmentations and derived clinical parameters were processed in ~90 seconds per case on a Xeon E5-2637v4 workstation with Tesla P40 GPUs. Clinical parameters and predicted segmentations exhibit high concordance with the ground truth regarding median perfusion for all lobes with an ICC of 0.99 and a Sørensen-Dice coefficient of 93.4 ± 2.8 (μ ± σ).

Data Conclusion: We present a robust end-to-end pipeline that allows for the extraction of perfusion-based biomarkers for all lung lobes in 4D DCE MRI scans by combining model-free deconvolution with deep learning.

Level Of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:571-579.
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http://dx.doi.org/10.1002/jmri.26853DOI Listing
February 2020
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