Publications by authors named "Wenting Wu"

193 Publications

Printing dynamic color palettes and layered textures through modeling-guided stacking of electrochromic polymers.

Mater Horiz 2021 Nov 14. Epub 2021 Nov 14.

Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.

In printable electrochromic polymer (ECP) displays, a wide color gamut, precise patterning, and controllable color switching are important. However, it is a significant challenge to achieve such features synergistically. Here, we present a solution-processable ECP stacking scheme, where a crosslinker is co-processed with three primary ECPs (ECP-Cyan, ECP-Magenta, and ECP-Yellow), which endows the primary ECPs with solvent-resistant properties and allows them to be sequentially deposited. varying the film thickness of each ECP layer, a full-color palette can be constructed. The ECP stacking strategy is further integrated with photolithography. Delicate multilayer patterns with overhang and undercut textures can be generated, allowing information displays with spatial dimensionality. In addition, modulating the stacking sequence, the electrochemical onset potentials of the ECP components can be synchronized to reduce unwanted intermediate colors that are often found in co-processed ECPs. Should specific color properties be desired, COMSOL modeling could be applied to guide the stacking. We believe that this ECP stacking strategy opens a new avenue for electrochromic printing and displays.
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http://dx.doi.org/10.1039/d1mh01098kDOI Listing
November 2021

Exploration of Ziziphi Spinosae Semen in Treating Insomnia Based on Network Pharmacology Strategy.

Evid Based Complement Alternat Med 2021 28;2021:9888607. Epub 2021 Oct 28.

Jiangxi University of Chinese Medicine, Nanchang, China.

Ziziphi Spinosae Semen (ZSS) is a common natural medicine used to treat insomnia, and to show clearly its method of action, we managed and did an in-depth discussion. Network pharmacology research is very suitable for the analysis of multiple components, multiple targets, and multiple pathways of Traditional Chinese Medicine (TCM). According to the relevant theory, we first carefully collected and screened the active ingredients in ZSS and received 11 active ingredients that may work. The targets going along with these active components were also strongly related to insomnia targets, 108 common genes were identified, and drug-compound-gene symbol-disease visualization network and protein-protein interaction network were constructed. Forty-eight core genes were identified by PPI analysis and subjected to GO functional analysis with KEGG pathway analysis. The results of GO analysis pointed that there were 998 gene ontology items for the treatment of insomnia, including terms of 892 biological processes, 47 cellular components, and 59 molecular functions. It mainly shows the coupling effect and transport mode of some proteins in the biological pathways of ZSS in the treatment of insomnia and explains the mechanism of action through the connection between the target and the cell biomembrane. KEGG enrichment analyzed 19 signaling pathways, which were collectively classified into seven categories. We have identified the potential pathways of ZSS against insomnia and obtained the regulatory relationship between core genes and pathways and know that the same target can be regulated by multiple components at the same time. The results of molecular docking also prove this conclusion. We sought to provide a new analytical approach to explore TCM treatments for diseases using network pharmacology analysis tools.
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http://dx.doi.org/10.1155/2021/9888607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568550PMC
October 2021

The Impact of Pro-Inflammatory Cytokines on Alternative Splicing Patterns in Human Islets.

Diabetes 2021 Oct 25. Epub 2021 Oct 25.

Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, Indiana

Alternative splicing (AS) within the β cell has been proposed as one potential pathway that may exacerbate autoimmunity and unveil novel immunogenic epitopes in type 1 diabetes (T1D). We employed a computational strategy to prioritize pathogenic splicing events in human islets treated with IL-1β + IFN-γ as an model of T1D and coupled this analysis with a k-mer based approach to predict RNA binding proteins involved in AS. In total, 969 AS events were identified in cytokine-treated islets, with the majority (44.8%) involving a skipped exon. ExonImpact identified 129 events predicted to impact protein structure. AS occurred with high frequency in MHC Class II-related mRNAs, and targeted qPCR validated reduced inclusion of Exon5 in the MHC Class II gene HLA-DMB. Single molecule RNA FISH confirmed increased HLA-DMB splicing in pancreatic sections from human donors with established T1D and autoantibody positivity. Serine and Arginine Rich Splicing Factor 2 was implicated in 37.2% of potentially pathogenic events, including Exon5 exclusion in HLA-DMB. Together, these data suggest that dynamic control of AS plays a role in the β cell response to inflammatory signals during T1D evolution.
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http://dx.doi.org/10.2337/db20-0847DOI Listing
October 2021

Kudzu Resistant Starch: An Effective Regulator of Type 2 Diabetes Mellitus.

Oxid Med Cell Longev 2021 13;2021:4448048. Epub 2021 Oct 13.

Key Laboratory of Modern Preparation of Traditional Chinese Medicines, Ministry of Education, Jiangxi University of Chinese Medicine, 330004 Nanchang, China.

Kudzu is a traditional medicinal dietary supplement, and recent research has shown its significant benefits in the prevention/treatment of type 2 diabetes mellitus (T2DM). Starch is one of the main substances in Kudzu that contribute decisively to the treatment of T2DM. However, the underlying mechanism of the hypoglycemic activity is not clear. In this study, the effect of Kudzu resistant starch supplementation on the insulin resistance, gut physical barrier, and gut microbiota was investigated in T2DM mice. The result showed that Kudzu resistant starch could significantly decrease the value of fasting blood glucose and the levels of total cholesterol, total triglyceride, and high-density lipoprotein, as well as low-density lipoprotein, in the blood of T2DM mice. The insulin signaling sensitivity in liver tissue was analyzed; the result indicated that intake of different doses of Kudzu resistant starch can help restore the expression of IRS-1, p-PI3K, p-Akt, and Glut4 and thus enhance the efficiency of insulin synthesis. Furthermore, the intestinal microorganism changes before and after ingestion of Kudzu resistant starch were also analyzed; the result revealed that supplementation of KRS helps to alleviate and improve the dysbiosis of the gut microbiota caused by T2DM. These results validated that Kudzu resistant starch could improve the glucose sensitivity of T2DM mice by modulating IRS-1/PI3K/AKT/Glut4 signaling transduction. Kudzu resistant starch can be used as a promising prebiotic, and it also has beneficial effects on the gut microbiota structure of T2DM mice.
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http://dx.doi.org/10.1155/2021/4448048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528595PMC
October 2021

Correction to: Boosting Transport Kinetics of Ions and Electrons Simultaneously by TiCT (MXene) Addition for Enhanced Electrochromic Performance.

Nanomicro Lett 2021 Oct 21;13(1):214. Epub 2021 Oct 21.

School of Electronic and Information Engineering and State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-021-00739-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531171PMC
October 2021

Tracking the environmental impacts of ecological engineering on coastal wetlands with numerical modeling and remote sensing.

J Environ Manage 2021 Oct 19;302(Pt A):113957. Epub 2021 Oct 19.

State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai, China.

Coastal wetlands are the most valuable ecosystems on the earth but facing severe degradation and losses owing to climate change and anthropogenic activities. Many ecological engineering projects (EEP) have been conducted to mitigate the degradation of coastal wetlands. However, the geomorphological impacts of EEP on coastal wetlands have not been well documented. In this study, a method employed a process-based hydrodynamic model and remote sensing (RS) was developed to evaluate the impacts of EEP on the geomorphological change of a prototype Ramsar site. Results demonstrated that RS can improve the quality of bathymetry data for the numerical model with a decrease of RMSE of bathymetry data from 0.52 m to 0.3 m. RS data also showed good capacity in trend detection of geomorphological change spatially. Results showed the Chongming Dongtan wetland experienced erosion with an annual rate of -0.035 m/yr from 2013 to 2016 after the implementation of EEP. The deposition rate changed significantly in the area within 200 m of the EEP. It is found that the EEP modified the composition of vegetation, sediment transportation, as well as substrate stability, affecting the geomorphological change of coastal wetlands. The study suggested that the EEP is a direct and effective way to restore the coastal habitats for waterbirds from moderate anthropogenic disturbance. However, the modification of the coastal wetland ecosystem by EEP will potentially increase the vulnerability to global climate change. Therefore, Future studies are needed to further evaluate the advantages and disadvantages of EEP and identify a more sustainable approach for coastal management.
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http://dx.doi.org/10.1016/j.jenvman.2021.113957DOI Listing
October 2021

Deoxyhypusine synthase promotes a pro-inflammatory macrophage phenotype.

Cell Metab 2021 Sep;33(9):1883-1893.e7

Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. Electronic address:

The metabolic inflammation (meta-inflammation) of obesity is characterized by proinflammatory macrophage infiltration into adipose tissue. Catalysis by deoxyhypusine synthase (DHPS) modifies the translation factor eIF5A to generate a hypusine (Hyp) residue. Hypusinated eIF5A (eIF5A) controls the translation of mRNAs involved in inflammation, but its role in meta-inflammation has not been elucidated. Levels of eIF5A were found to be increased in adipose tissue macrophages from obese mice and in murine macrophages activated to a proinflammatory M1-like state. Global proteomics and transcriptomics revealed that DHPS deficiency in macrophages altered the abundance of proteins involved in NF-κB signaling, likely through translational control of their respective mRNAs. DHPS deficiency in myeloid cells of obese mice suppressed M1 macrophage accumulation in adipose tissue and improved glucose tolerance. These findings indicate that DHPS promotes the post-transcriptional regulation of a subset of mRNAs governing inflammation and chemotaxis in macrophages and contributes to a proinflammatory M1-like phenotype.
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http://dx.doi.org/10.1016/j.cmet.2021.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432737PMC
September 2021

Fine mapping and identification of the candidate gene BFS for fruit shape in wax gourd (Benincasa hispida).

Theor Appl Genet 2021 Dec 4;134(12):3983-3995. Epub 2021 Sep 4.

College of Agriculture, Guangxi University, Guangxi, 530004, China.

Key Message: Non-synonymous mutations in the BFS gene, which encodes the IQD protein, are responsible for the shape of wax gourd fruits. Fruit shape is an important agronomic trait in wax gourds. Therefore, in this study, we employed bulked segregant analysis (BSA) to identify a candidate gene for fruit shape in wax gourds within F populations derived by crossing GX-71 (long cylindrical fruit, fruit shape index = 4.56) and MY-1 (round fruit, fruit shape index = 1.06) genotypes. According to BSA, the candidate gene is located in the 17.18 Mb region on chromosome 2. Meanwhile, kompetitive allele-specific PCR (KASP) markers were used to reduce it to a 19.6 Kb region. Only one gene was present within the corresponding region of the reference genome, namely Bch02G016830 (designated BFS). Subsequently, BFS was sequenced in six wax gourd varieties with different fruit shapes. Sequence analysis revealed two non-synonymous mutations in the round wax gourd and one non-synonymous mutation in the cylindrical wax gourd. Quantitative real‑time PCR (qRT-PCR) analysis further showed that the expression of BFS in round fruits was significantly higher than in long cylindrical fruits at the ovary formation stage. Therefore, BFS is a candidate gene for determination wax gourd shape. The predicted protein encoded by the BFS gene belongs to the IQ67-domain protein family, which have the structural characteristics of scaffold proteins and coordinate Ca CaM signaling from the membrane to the nucleus. Ultimately, two derived cleaved amplified polymorphic sequence (dCAPS) markers were developed to facilitate marker-assisted selection for wax gourds breeding.
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http://dx.doi.org/10.1007/s00122-021-03942-8DOI Listing
December 2021

Cu,Zn Dopants Boost Electron Transfer of Carbon Dots for Antioxidation.

Small 2021 08 1;17(31):e2102178. Epub 2021 Jul 1.

State Key Laboratory of Heavy Oil Processing, College of Chemical Engineering, Institute of New Energy, China University of Petroleum (East China), Qingdao, 266580, China.

Enzyme-mimicking nanomaterials for antioxidative therapy is a promising star to treat more than 200 diseases or control their progressions through scavenging excessive reactive oxygen species (ROS), such as O and H O . However, they can inversely produce stronger ROS (e.g., •OH) under many disease conditions (e.g., low pH for myocardial ischemia). Herein, a biocompatible -Cu-O-Zn- bimetallic covalent doped carbon dots (CuZn-CDs) processing both catalase (CAT) and superoxide dismutase activities are reported, mainly because of their abundant electrons and the excellent electron transfer abilities. In addition, Cu dopant helps to balance the positive charge at Zn dopant resulting from low pH, enabling CuZn-CDs to still process CAT ability rather than peroxidase ability. Benefiting from it, CuZn-CDs exhibit sufficient in vitro ROS scavenging ability and cardiomyocyte protective effect against ROS-induced damage. In vivo results further demonstrate that CuZn-CDs can protect the heart from ischemia-reperfusion injury. In addition to antioxidative therapy, the rapid renal clearance and low toxicity properties of CuZn-CDs in animal model reveal high biocompatibility which will facilitate clinical use.
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http://dx.doi.org/10.1002/smll.202102178DOI Listing
August 2021

A self-powered photoelectrochemical ultraviolet photodetector based on TiCT/TiOformed heterojunctions.

Nanotechnology 2021 Nov 24;33(7). Epub 2021 Nov 24.

Department of Materials Science and Engineering & Shenzhen Engineering Research Center for Novel Electronic Information Materials and Devices, Southern University of Science and Technology, Shenzhen 518055, People's Republic of China.

Transition metal carbides and nitrides (MXenes), as a large family of emerging two-dimensional materials, have demonstrated extraordinary performance in many fields such as electronics, optics and energy storage. However, their susceptibility to oxidation during preparation and storage in ambient air environment is undesirable for long-term and stable applications. Here, we have demonstrated that the spontaneous oxidation of TiCTcan be harnessed ingeniously to prepare TiCT/TiOformed heterojunctions. Furthermore, a self-powered ultraviolet photodetector was constructed based on the photoelectrochemical performance of TiCT/TiOheterojunctions. Since the highly conductive TiCTcan promote the separation and transfer of photogenerated carriers in TiO, the prepared photodetector exhibits high responsivity (2.06 mA W), short rise and decay times (45 and 69 ms) and long-term stability. This work demonstrates the controllable synthesis of TiCT/TiOheterojunctions and provides a new promising potential of MXenes for photodetection applications.
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http://dx.doi.org/10.1088/1361-6528/ac0eaaDOI Listing
November 2021

Boosting Transport Kinetics of Ions and Electrons Simultaneously by TiCT (MXene) Addition for Enhanced Electrochromic Performance.

Nanomicro Lett 2020 Nov 6;13(1):20. Epub 2020 Nov 6.

School of Electronic and Information Engineering and State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, People's Republic of China.

Electrochromic technology plays a significant role in energy conservation, while its performance is greatly limited by the transport behavior of ions and electrons. Hence, an electrochromic system with overall excellent performances still need to be explored. Initially motivated by the high ionic and electronic conductivity of transition metal carbide or nitride (MXene), we design a feasible procedure to synthesize the MXene/WO composite electrochromic film. The consequently boosted electrochromic performances prove that the addition of MXene is an effective strategy for simultaneously enhancing electrons and ions transport behavior in electrochromic layer. The MXene/WO electrochromic device exhibits enhanced transmittance modulation and coloration efficiency (60.4%, 69.1 cm C), higher diffusion coefficient of Li and excellent cycling stability (200 cycles) over the pure WO device. Meanwhile, numerical stimulation theoretically explores the mechanism and kinetics of the lithium ion diffusion, and proves the spatial and time distributions of higher Li concentration in MXene/WO composite electrochromic layer. Both experiments and theoretical data reveal that the addition of MXene is effective to promote the transport kinetics of ions and electrons simultaneously and thus realizing a high-performance electrochromic device. This work opens new avenues for electrochromic materials design and deepens the study of kinetics mechanism of ion diffusion in electrochromic devices.
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http://dx.doi.org/10.1007/s40820-020-00544-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187520PMC
November 2020

Self-Powered Rewritable Electrochromic Display based on WO Film with Mechanochemically Synthesized MoO Nanosheets.

ACS Appl Mater Interfaces 2021 May 21;13(17):20326-20335. Epub 2021 Apr 21.

School of Electronic and Information Engineering and State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, P. R. China.

Electrochromic displays with bistable color states provide a promising means toward transparent human-machine interfaces. However, the need for external power and the weak optical modulation in the visible light region of most electrochromic devices hinder their practical applications in displays. Here we prepare the MoO/WO films based on MoO nanosheets, which show a dark blue color that matches the response of the eye and meets visual comfort standards compared to pure WO film. By introducing the highly transparent Al ion hydrogel layer, a convenient electrochromic device driven by the internal chemical potential has been designed. The device based on the MoO /WO film exhibits a high optical modulation in the whole visible light range and can operate at self-powered mode with fast response speed and excellent cycle stability. Moreover, we develop an ionic writing board based on the MoO/WO film to surmount the fixed display information issue in conventional electrochromic displays. The ionic writing board exhibits excellent visual display quality and realizes arbitrary writing with a self-powered characteristic. This work provides a simple mechanochemical synthesis procedure of MoO nanosheets and an ingenious design of self-powered electrochromic devices, which will enable the development of next-generation high-performance electrochromic displays.
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http://dx.doi.org/10.1021/acsami.1c01959DOI Listing
May 2021

Deoxyhypusine synthase, an essential enzyme for hypusine biosynthesis, is required for proper exocrine pancreas development.

FASEB J 2021 05;35(5):e21473

Indiana Biosciences Research Institute, Indianapolis, IN, USA.

Pancreatic diseases including diabetes and exocrine insufficiency would benefit from therapies that reverse cellular loss and/or restore cellular mass. The identification of molecular pathways that influence cellular growth is therefore critical for future therapeutic generation. Deoxyhypusine synthase (DHPS) is an enzyme that post-translationally modifies and activates the mRNA translation factor eukaryotic initiation factor 5A (eIF5A). Previous work demonstrated that the inhibition of DHPS impairs zebrafish exocrine pancreas development; however, the link between DHPS, eIF5A, and regulation of pancreatic organogenesis remains unknown. Herein we identified that the conditional deletion of either Dhps or Eif5a in the murine pancreas results in the absence of acinar cells. Because DHPS catalyzes the activation of eIF5A, we evaluated and uncovered a defect in mRNA translation concomitant with defective production of proteins that influence cellular development. Our studies reveal a heretofore unappreciated role for DHPS and eIF5A in the synthesis of proteins required for cellular development and function.
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http://dx.doi.org/10.1096/fj.201903177RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034418PMC
May 2021

Understanding the Synergistic Correlation between the Spatial Distribution of Drug-Loaded Mixed Micellar Systems and Behavior Experimental and Computational Approaches.

Mol Pharm 2021 04 24;18(4):1643-1655. Epub 2021 Mar 24.

Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.

To better promote the application of polymeric mixed micelles (PMMs), a coarse-grained molecular dynamics simulation (CGMD) has been employed to investigate the factors controlling the spatial distribution within the PMMs and predict their drug-loading properties, meanwhile, combined with experimental methods to validate and examine it. In this study, the snapshots obtained from CGMD and the results of proton nuclear magnetic resonance (H NMR) and transmission electron microscopy (TEM) provide new insights into the distribution principle that the spatial distribution depends on the hydrophobic compatibility of drugs with the regions within PMMs. Docetaxel (DTX) is located within the interior or near the core-corona interface of the HS15 hydrophobic core inside FS/PMMs (PMMs fabricated from a nonionic triblock copolymer (F127)) and a nonionic surfactant (HS15), and therefore, the system with a high HS15 ratio, such as system I, is more suitable for loading DTX. In contrast, the more water-soluble puerarin (PUE) is more likely to be solubilized in the "secondary hydrophobic area," mainly formed by the hydrophobic part of F127 within FS/PMMs. However, when the initial feeding concentration of the drug is increased or the FS mixing ratios are changed, an inappropriate distribution would occur and hence influence the drug-loading stability. Also, this impact was further elucidated by the calculated parameters (solvent-accessible surface area (SASA), the radius of gyration (), and energy landscape), and the analysis of the drug leakage, concluding that inappropriate distribution of the drug would lower the stability of the drug in the PMMs. These results combined together provide new insights into the distribution principle that the spatial distribution of drugs within PMMs depends on the hydrophobic compatibility of drugs with the regions formed by micellar materials. Additionally, drug release yielded a consistent picture with the above conclusions and provides evidence that both the location of the drug within the systems and the stability of the drug-loading system have a great influence on the drug release behavior. Accordingly, this work demonstrates that we can tune the drug-loading stability and drug release behavior the drug-PMM interaction and drug location study, and CGMD technology would be a step forward in the search for suitable drug-delivery PMMs.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01095DOI Listing
April 2021

Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer.

Int J Epidemiol 2021 08;50(4):1325-1334

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Background: Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases.

Methods: We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02-1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08-1.38, Ptrend = 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus.

Conclusion: These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.
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http://dx.doi.org/10.1093/ije/dyab042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521875PMC
August 2021

Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color.

Sci Adv 2021 Mar 10;7(11). Epub 2021 Mar 10.

Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.
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http://dx.doi.org/10.1126/sciadv.abd1239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946369PMC
March 2021

Fe/Fe C Boosts H O Utilization for Methane Conversion Overwhelming O Generation.

Angew Chem Int Ed Engl 2021 Apr 10;60(16):8889-8895. Epub 2021 Mar 10.

State Key Laboratory of Heavy Oil Processing, Institute of New Energy, College of Chemical Engineering, China University of Petroleum (East China), Qingdao, 266580, P. R. China.

H O as a well-known efficient oxidant is widely used in the chemical industry mainly because of its homolytic cleavage into OH (stronger oxidant), but this reaction always competes with O generation resulting in H O waste. Here, we fabricate heterogeneous Fenton-type Fe-based catalysts containing Fe-N sites and Fe/Fe C nanoparticles as a model to study this competition. Fe-N in the low spin state provides the active site for OH generation. Fe/Fe C, in particular Fe C, promotes Fe-N sites for the homolytic cleavages of H O into OH, but Fe/Fe C nanoparticles (Fe as the main component) with more electrons are prone to the undesired O generation. With a catalyst benefiting from finely tuned active sites, 18 % conversion rate for the selective oxidation of methane was achieved with about 96 % selectivity for liquid oxygenates (formic acid selectivity over 90 %). Importantly, O generation was suppressed 68 %. This work provides guidance for the efficient utilization of H O in the chemical industry.
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http://dx.doi.org/10.1002/anie.202016888DOI Listing
April 2021

Single-Cell Transcriptional Profiling of Mouse Islets Following Short-Term Obesogenic Dietary Intervention.

Metabolites 2020 Dec 18;10(12). Epub 2020 Dec 18.

Kolver Diabetes Center and Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.

Obesity is closely associated with adipose tissue inflammation and insulin resistance. Dysglycemia and type 2 diabetes results when islet β cells fail to maintain appropriate insulin secretion in the face of insulin resistance. To clarify the early transcriptional events leading to β-cell failure in the setting of obesity, we fed male C57BL/6J mice an obesogenic, high-fat diet (60% kcal from fat) or a control diet (10% kcal from fat) for one week, and islets from these mice (from four high-fat- and three control-fed mice) were subjected to single-cell RNA sequencing (sc-RNAseq) analysis. Islet endocrine cell types (α cells, β cells, δ cells, PP cells) and other resident cell types (macrophages, T cells) were annotated by transcript profiles and visualized using Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP) plots. UMAP analysis revealed distinct cell clusters (11 for β cells, 5 for α cells, 3 for δ cells, PP cells, ductal cells, endothelial cells), emphasizing the heterogeneity of cell populations in the islet. Collectively, the clusters containing the majority of β cells showed the fewest gene expression changes, whereas clusters harboring the minority of β cells showed the most changes. We identified that distinct β-cell clusters downregulate genes associated with the endoplasmic reticulum stress response and upregulate genes associated with insulin secretion, whereas others upregulate genes that impair insulin secretion, cell proliferation, and cell survival. Moreover, all β-cell clusters negatively regulate genes associated with immune response activation. Glucagon-producing α cells exhibited patterns similar to β cells but, again, in clusters containing the minority of α cells. Our data indicate that an early transcriptional response in islets to an obesogenic diet reflects an attempt by distinct populations of β cells to augment or impair cellular function and/or reduce inflammatory responses as possible harbingers of ensuing insulin resistance.
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http://dx.doi.org/10.3390/metabo10120513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765825PMC
December 2020

Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19.

Cell Metab 2020 12 13;32(6):1041-1051.e6. Epub 2020 Nov 13.

Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA; Department of Pediatrics, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA. Electronic address:

Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.
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http://dx.doi.org/10.1016/j.cmet.2020.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664515PMC
December 2020

Highly Effective Near-Infrared Activating Triplet-Triplet Annihilation Upconversion for Photoredox Catalysis.

J Am Chem Soc 2020 10 19;142(43):18460-18470. Epub 2020 Oct 19.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.

Organic triplet-triplet annihilation upconversion (TTA-UC) materials have considerable promise in areas as broad as biology, solar energy harvesting, and photocatalysis. However, the development of highly efficient near-infrared (NIR) light activatable TTA-UC systems remains extremely challenging. In this work, we report on a method of systematically tailoring an annihilator to attain such outstanding systems. By chemical modifications of a commonly used perylene annihilator, we constructed a family of perylene derivatives that have simultaneously tailored triplet excited state energy (T) and singlet excited state energy (S), two key annihilator factors to determine TTA-UC performance. this method, we were able to tune the TTA-UC system from an endothermic type to an exothermic one, thus significantly elevating the upconversion performance of NIR light activatable TTA upconversion systems. In conjunction with the photosensitizer PdTNP (10 μM), the upconversion efficiency using the optimal annihilator (100 μM) identified in this study was measured to be 14.1% under the low-power density of NIR light (100 mW/cm, 720 nm). Furthermore, using such a low concentration of perylene derivative, we demonstrated that the optimal TTA-UC pair developed in our study can act as a highly effective light wavelength up-shifter to enable NIR light to drive a photoredox catalysis that otherwise requires visible light. We found that such an NIR driven method is highly effective and can even surpass directly visible light driven photoredox catalysis. This method is important for photoredox catalysis as NIR light can penetrate much deeper in colored photoredox catalysis reaction solutions, especially when done in a large-scale manner. Furthermore, this TTA-UC mediated photoredox catalysis reaction is found to be outdoor sunlight operable. Thus, our study provides a solution to enhance NIR activatable organic upconversion and set the stage for a wide array of applications that have previously been limited by the suboptimal efficiency of the existing TTA upconversion materials.
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http://dx.doi.org/10.1021/jacs.0c06976DOI Listing
October 2020

Alkali Halide Boost of Carbon Nitride for Photocatalytic H Evolution in Seawater.

ACS Appl Mater Interfaces 2020 Oct 13;12(43):48526-48532. Epub 2020 Oct 13.

State Key Laboratory of Heavy Oil Processing, College of Chemical Engineering, China University of Petroleum (East China), No. 66 Changjiang West Road, Qingdao 266580, P. R. China.

Photocatalytic H evolution (PHE) from extremely abundant seawater resources is an ideal way to secure sustainable H for humanity, but the saline in seawater easily competitively absorbs the active sites and poisons the catalyst. Herein, a series of low-cost alkali halide (NaI, KI, RbI, CsI, CsBr, and CsCl), analogous to the saline in natural seawater, was selected to modify carbon nitride (MX-CN) through one-step facile pyrolysis with the assistance of water. MX-CN possesses a large amount of negative charges, which could inhibit anion absorption, to some extent, preventing chloride corrosion. Importantly, it can greatly boost the electron transfer between MX-CN and triethanolamine (TEOA) (sacrificial agent) because the alkali cation in seawater can coordinate with TEOA, and easily come in contact with MX-CN through alkali-cation exchange and electrostatic attraction. Benefiting from it, the PHE performance in seawater is 200 times better than that of original CN in deionized water above, and the apparent quantum efficiency of MX-CN (CsI-CN) under 420 nm light irradiation comes to 72% in seawater, the highest value reported for seawater thus far. This work provides a new research direction for engineering the electron transfer pathway between the photocatalyst and sacrificial agent (e.g., pollutant) in natural seawater.
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http://dx.doi.org/10.1021/acsami.0c13060DOI Listing
October 2020

STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus.

Nat Commun 2020 09 28;11(1):4882. Epub 2020 Sep 28.

Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

T helper cell differentiation requires lineage-defining transcription factors and factors that have shared expression among multiple subsets. BATF is required for development of multiple Th subsets but functions in a lineage-specific manner. BATF is required for IL-9 production in Th9 cells but in contrast to its function as a pioneer factor in Th17 cells, BATF is neither sufficient nor required for accessibility at the Il9 locus. Here we show that STAT5 is the earliest factor binding and remodeling the Il9 locus to allow BATF binding in both mouse and human Th9 cultures. The ability of STAT5 to mediate accessibility for BATF is observed in other Th lineages and allows acquisition of the IL-9-secreting phenotype. STAT5 and BATF convert Th17 cells into cells that mediate IL-9-dependent effects in allergic airway inflammation and anti-tumor immunity. Thus, BATF requires the STAT5 signal to mediate plasticity at the Il9 locus.
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http://dx.doi.org/10.1038/s41467-020-18648-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523001PMC
September 2020

Olaparib monotherapy for Asian patients with a germline BRCA mutation and HER2-negative metastatic breast cancer: OlympiAD randomized trial subgroup analysis.

Sci Rep 2020 05 29;10(1):8753. Epub 2020 May 29.

National Hospital Organization, Osaka National Hospital, Osaka, Japan.

The OlympiAD Phase III study (NCT02000622) established the clinical benefits of olaparib tablet monotherapy (300 mg twice daily) over chemotherapy treatment of physician's choice (TPC) in patients with a germline BRCA1/2 mutation (gBRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who had received ≤2 chemotherapy lines in the metastatic setting. Here, we report pre-specified analyses of data from Asian (China, Japan, Korea and Taiwan) patients in the study. All patients were randomized 2:1 to olaparib tablets (300 mg twice daily) or single-agent chemotherapy TPC (21-day cycles of either capecitabine, eribulin or vinorelbine). The primary endpoint was progression-free survival assessed by blinded independent central review. The prevalence of gBRCAm in the OlympiAD Asian subgroup screened for study recruitment was 13.5%. Patient demographics and disease characteristics of the Asian subgroup (87/302 patients) were generally well balanced between treatment arms. Asian patients in the olaparib arm achieved longer median progression-free survival, assessed by blinded independent central review, versus the chemotherapy TPC arm (5.7 vs 4.2 months; HR = 0.53 [95% CI: 0.29-0.97]), which was consistent with findings in the global OlympiAD study population. Findings on secondary efficacy and safety/tolerability outcome measures in Asian patients were also similar to those observed in the global OlympiAD study population. The OlympiAD study was not powered to detect race-related differences between treatment groups; however, the consistency of our findings with the global OlympiAD study population suggests that previously reported findings are generalizable to Asian patients.
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http://dx.doi.org/10.1038/s41598-020-63033-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260217PMC
May 2020

Proteomic analysis of liver proteins of mice exposed to 1,2-dichloropropane.

Arch Toxicol 2020 08 20;94(8):2691-2705. Epub 2020 May 20.

Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan.

1,2-Dichloropropane (1,2-DCP) is recognized as the causative agent for cholangiocarcinoma among offset color proof-printing workers in Japan. The aim of the present study was to characterize the molecular mechanisms of 1,2-DCP-induced hepatotoxic effects by proteomic analysis. We analyzed quantitatively the differential expression of proteins in the mouse liver and investigated the role of P450 in mediating the effects of 1,2-DCP. Male C57BL/6JJcl mice were exposed to 0, 50, 250, or 1250 ppm 1,2-DCP and treated with either 1-aminobenzotriazole (1-ABT), a nonselective P450 inhibitor, or saline, for 8 h/day for 4 weeks. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF/MS) was used to detect and identify proteins affected by the treatment. PANTHER overrepresentation test on the identified proteins was conducted. 2D-DIGE detected 61 spots with significantly different intensity between 0 and 250 ppm 1,2-DCP groups. Among them, 25 spots were identified by MALDI-TOF/TOF/MS. Linear regression analysis showed significant trend with 1,2-DCP level in 17 proteins in mice co-treated with 1-ABT. 1-ABT mitigated the differential expression of these proteins. The gene ontology enrichment analysis showed overrepresentation of proteins functionally related to nickel cation binding, carboxylic ester hydrolase activity, and catalytic activity. The results demonstrated that exposure to 1,2-DCP altered the expression of proteins related with catalytic and carboxylic ester hydrolase activities, and that such effect was mediated by P450 enzymatic activity.
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http://dx.doi.org/10.1007/s00204-020-02785-4DOI Listing
August 2020

Assessment of 5-Aminolaevulinic Acid Photodynamic Therapy (ALA-PDT) in Chinese patients with actinic keratosis: Correlation of dermoscopic features with histopathology.

Australas J Dermatol 2020 Aug 18;61(3):e339-e343. Epub 2020 May 18.

Department of Dermatology, Peking University Third Hospital, Beijing, China.

Objectives: The study examines the changes in dermoscopic features of actinic keratosis (AK) after photodynamic therapy, and delineates the association between AK dermoscopic and histopathological findings.

Methods: A total of 21 patients (23 lesions) with pathologically confirmed actinic keratosis who received 5-aminolaevulinic acid (ALA) photodynamic therapy (ALA-PDT) were enrolled. The numbers of PDT treatments were: 1, n = 1; 2, n = 2; 3, n = 10; 4, n = 6; 5, n = 2; 6, n = 2). The dermoscopic features before and after the PDT were compared.

Results: There were statistically significant decreases in the positive rates of dermoscopic features including scales (P < 0.001), follicular plugs with whitish halo (P = 0.013), and red pseudonetwork (P = 0.022) among patients treated with ALA-PDT. Dermoscopic feature was significantly associated with pathological grade (P < 0.001). Histopathological hyperkeratosis was significantly associated with dermoscopic red pseudonetwork (P = 0.034) and wavy vessel (P = 0.005). Parakeratosis was associated with wavy vessels (P = 0.001). For vascular hyperplasia in dermal papillae, the significant correlates included scales (P = 0.011), follicular plugs with whitish halo (P = 0.011), red pseudonetwork (P < 0.001); coiled vessels (P = 0.003) and rosette sign (P = 0.004). Wavy vessels was the only feature correlating keratosis pilaris (P = 0.003).

Conclusions: The findings of the present study support dermoscopy as having potential to be useful for diagnosing and monitoring of actinic keratosis.
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http://dx.doi.org/10.1111/ajd.13289DOI Listing
August 2020

Exploring the dynamics and interplay of human papillomavirus and cervical tumorigenesis by integrating biological data into a mathematical model.

BMC Bioinformatics 2020 May 5;21(Suppl 7):152. Epub 2020 May 5.

College of Computer Science, Sichuan University, Chengdu, 610065, China.

Background: Cervical cancer is the fourth most common tumor in women worldwide, mostly resulting from high-risk human papillomavirus (HR-HPV) with persistent infection.

Results: The present discoveries are comprised of the following: (i) A total of 16.64% of the individuals were positive for HR-HPV infection, with 13.04% having a single HR-HPV type and 3.60% having multiple HR-HPV types. (ii) Cluster analysis showed that the infection rate trends of HPV31 and HPV33 in all infections as well as HPV33 and HPV35 in single infections in precancerous stages were very similar. (iii) The single/multiple infection proportions of HR-HPV demonstrated a trend that the multiple infections rates of HR-HPV increased as the disease developed.

Conclusions: The HR-HPV prevalence in outpatients was 16.64%, and the predominant HR-HPV types in the study were HPV52, HPV58 and HPV16. HR-HPV subtypes with common biological properties had similar infection rate trends in precancerous stages. Especially, as the disease development of precancer evolved, defense against HPV infection broke, meanwhile, the potential of more HPV infection increased, which resulted in increase of multiple infections of HPV.
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http://dx.doi.org/10.1186/s12859-020-3454-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199323PMC
May 2020

Olaparib for Metastatic Castration-Resistant Prostate Cancer.

N Engl J Med 2020 05 28;382(22):2091-2102. Epub 2020 Apr 28.

From the Institute of Cancer Research and Royal Marsden Hospital, London (J. de Bono), and AstraZeneca, Translational Medicine, Cambridge (C.A.A.) - all in the United Kingdom; Vall d'Hebron Institute of Oncology and Vall d'Hebron University Hospital, Barcelona (J.M.), the Spanish National Cancer Research Center, Madrid (D.O.), and Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Malaga (D.O.) - all in Spain; Institut Gustave Roussy, University of Paris Sud, Villejuif (K.F.), and the Department of Medical Oncology, Centre Hospitalier Universitaire Besançon, Besançon (A.T.-V.) - all in France; Centre Hospitalier de l'Université de Montréal-Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal (F.S.), and BC Cancer Agency, Vancouver (K.N.C.) - all in Canada; Carolina Urologic Research Center, Myrtle Beach, SC (N.S.); Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (S.S.); Tulane University School of Medicine, New Orleans (O.S.); Huntsman Cancer Institute, University of Utah Comprehensive Cancer Center, Salt Lake City (N.A.); John Wayne Cancer Institute, Santa Monica, CA (P.T.); Radboud University Medical Center, Nijmegen, the Netherlands (N.M.); AstraZeneca, Global Medicines Development, Oncology, Gaithersburg, MD (C.G., J.K., W.W.); Merck, Kenilworth, NJ (J. Burgents); AstraZeneca, Precision Medicine, Oncology Research and Development, Gaithersburg, MD (A.K.); and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago (M.H.).

Background: Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition in patients with prostate and other cancers.

Methods: We conducted a randomized, open-label, phase 3 trial evaluating the PARP inhibitor olaparib in men with metastatic castration-resistant prostate cancer who had disease progression while receiving a new hormonal agent (e.g., enzalutamide or abiraterone). All the men had a qualifying alteration in prespecified genes with a direct or indirect role in homologous recombination repair. Cohort A (245 patients) had at least one alteration in , , or ; cohort B (142 patients) had alterations in any of 12 other prespecified genes, prospectively and centrally determined from tumor tissue. Patients were randomly assigned (in a 2:1 ratio) to receive olaparib or the physician's choice of enzalutamide or abiraterone (control). The primary end point was imaging-based progression-free survival in cohort A according to blinded independent central review.

Results: In cohort A, imaging-based progression-free survival was significantly longer in the olaparib group than in the control group (median, 7.4 months vs. 3.6 months; hazard ratio for progression or death, 0.34; 95% confidence interval, 0.25 to 0.47; P<0.001); a significant benefit was also observed with respect to the confirmed objective response rate and the time to pain progression. The median overall survival in cohort A was 18.5 months in the olaparib group and 15.1 months in the control group; 81% of the patients in the control group who had progression crossed over to receive olaparib. A significant benefit for olaparib was also seen for imaging-based progression-free survival in the overall population (cohorts A and B). Anemia and nausea were the main toxic effects in patients who received olaparib.

Conclusions: In men with metastatic castration-resistant prostate cancer who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair, olaparib was associated with longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. (Funded by AstraZeneca and Merck Sharp & Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).
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http://dx.doi.org/10.1056/NEJMoa1911440DOI Listing
May 2020

Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Radix Puerariae for Treatment of Hypertension.

Front Pharmacol 2020 24;11:345. Epub 2020 Mar 24.

School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Hypertension is a clinical cardiovascular syndrome characterized by elevated systemic arterial pressure with or without multiple cardiovascular risk factors. Radix Pueraria (RP) has the effects of anti-myocardial ischemia, anti-arrhythmia, vasodilatation, blood pressure reduction, anti-inflammation, and attenuating insulin resistance. Although RP can be effective for the treatment of hypertension, its active compounds, drug targets, and exact molecular mechanism are still unclear. In this study, systems pharmacology was used to analyze the active compounds, drug target genes, and key pathways of RP in the treatment of hypertension. Thirteen active compounds and related information on RP were obtained from the TCMSP database, and 140 overlapping genes related to hypertension and drugs were obtained from the GeneCards and OMIM databases. A PPI network and a traditional Chinese medicine (TCM) comprehensive network (Drug-Compounds-Genes-Disease network) were constructed, and 2,246 GO terms and 157 pathways were obtained by GO enrichment analysis and KEGG pathway enrichment analysis. Some important active compounds and targets were evaluated by experiments. This study shows that RP probably acts by influencing the proliferation module, apoptosis module, inflammation module, and others when treating hypertension. This study provides novel insights for researchers to systematically explore the mechanism of action of TCM.
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http://dx.doi.org/10.3389/fphar.2020.00345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107014PMC
March 2020

Construction of Thiazole-Fused Dihydropyrans via Formal [4 + 2] Cycloaddition Reaction on DNA.

Org Lett 2020 04 3;22(8):3239-3244. Epub 2020 Apr 3.

Department of Therapeutic Discovery, Amgen Asia R&D Center, Amgen Research, 4560 Jinke Road, Pudong, Shanghai 201210, P. R. China.

An efficient and facile formal [4 + 2] cycloaddition reaction was developed to synthesize diverse thiazole-fused dihydropyrans (TFDP) on DNA. Mild reaction conditions, broad substrate scope, and compatibility with subsequent enzymatic ligation demonstrated the utility of this methodology in DNA-encoded library synthesis.
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http://dx.doi.org/10.1021/acs.orglett.0c01016DOI Listing
April 2020
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