Publications by authors named "Zhiyuan Ma"

148 Publications

Corrigendum to 'Physiological and pathophysiological roles of Acidic mammalian chitinase (CHIA) in multiple organs' [Biomed. Pharmacother. 138 (2021) 111465].

Biomed Pharmacother 2021 Jul 14;139:111699. Epub 2021 May 14.

Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province 563003, China; Digestive Disease Institute of Guizhou Province, Zunyi, Guizhou Province 563003, China; Endoscopy Center, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province 563003, China. Electronic address:

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http://dx.doi.org/10.1016/j.biopha.2021.111699DOI Listing
July 2021

Physiological and pathophysiological roles of acidic mammalian chitinase (CHIA) in multiple organs.

Biomed Pharmacother 2021 Jun 9;138:111465. Epub 2021 Apr 9.

Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province 563003, China; Digestive Disease Institute of Guizhou Province, Zunyi, Guizhou Province 563003, China; Endoscopy center, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province 563003, China. Electronic address:

Acidic mammalian chitinase (CHIA) belongs to the 18-glycosidase family and is expressed in epithelial cells and certain immune cells (such as neutrophils and macrophages) in various organs. Under physiological conditions, as a hydrolase, CHIA can degrade chitin-containing pathogens, participate in Type 2 helper T (Th2)-mediated inflammation, and enhance innate and adaptive immunity to pathogen invasion. Under pathological conditions, such as rhinitis, ocular conjunctivitis, asthma, chronic atrophic gastritis, type 2 diabetes, and pulmonary interstitial fibrosis, CHIA expression is significantly changed. In addition, studies have shown that CHIA has an anti-apoptotic effect, promotes epithelial cell proliferation and maintains organ integrity, and these effects are not related to chitinase degradation. CHIA can also be used as a biomolecular marker in diseases such as chronic atrophic gastritis, dry eye, and acute kidney damage caused by sepsis. Analysis of the authoritative TCGA database shows that CHIA expression in gastric adenocarcinoma, liver cancer, renal clear cell carcinoma and other tumors is significantly downregulated compared with that in normal tissues, but the specific mechanism is unclear. This review is based on all surveys conducted to date and summarizes the expression patterns and functional diversity of CHIA in various organs. Understanding the physiological and pathophysiological relevance of CHIA in multiple organs opens new possibilities for disease treatment.
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http://dx.doi.org/10.1016/j.biopha.2021.111465DOI Listing
June 2021

Multi-target mechanism of Hook for treatment of ankylosing spondylitis based on network pharmacology and molecular docking.

Ann Med 2021 12;53(1):1090-1098

Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Background: Hook (TWH) has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases. However, the multi-target mechanism of TWH on ankylosing spondylitis (AS) remains to be elucidated.

Methods: Active components and their target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Meanwhile, AS-related targets were obtained from the Genecards Database. After overlapping, the targets of TWH against AS were collected. Then protein-protein interaction (PPI) network and core targets analysis were conducted through STRING network platform and Cytoscape software. Moreover, molecular docking methods were utilized to confirm the high affinity between TWH and targets. Finally, DAVID online tool was used to perform gene ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) pathway enrichment analysis of overlapping targets.

Results: The TCMSP Database results showed that there were11 active components of TWH against AS. PPI network and core targets analysis suggested that ESR1, VEGF, ICAM-1, and RELA were key targets against AS. Moreover, molecular docking methods confirmed the high affinity between bioactive molecular of TWH and their targets in AS. At last, enrichment analysis indicated that TWH participates in various biological processes, such as cell-cell adhesion, regulation of cell-matrix adhesion, acute inflammatory response, via TNF-α, NF-κB and so forth signalling pathways.

Conclusion: Verified by network pharmacology approach based on data mining and molecular docking methods, multi-target drug TWH may serve as a promising therapeutic candidate for AS but still needs further / experiments.
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http://dx.doi.org/10.1080/07853890.2021.1918345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280885PMC
December 2021

Self-Assembled Polyoxometalate Nanodots as Bidirectional Cluster Catalysts for Polysulfide/Sulfide Redox Conversion in Lithium-Sulfur Batteries.

ACS Nano 2021 Jun 22. Epub 2021 Jun 22.

Key Lab of Organic Optoelectronics & Molecular Engineering of Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China.

Polyoxometalates (POMs) are a class of discrete molecular inorganic metal-oxide clusters with reversible multielectron redox capability. Taking advantage of their redox properties, POMs are thus expected to be directly involved in the lithium-sulfur batteries (Li-S, LSBs) system as a bidirectional molecular catalyst. Herein, we design a three-dimensional porous structure of reduced graphene-carbon nanotube skeleton supported POM catalyst as a high-conductive and high-stability host material. Based on various spectroscopic techniques and electrochemical studies together with computational methods, the catalytic mechanism of POM clusters in Li-S battery was systematically clarified at the molecular level. The constructed POM-based sulfur cathode delivers a reversible capacity 1110 mAh g at 1.0 C and cycling stability up to 1000 cycles at 3.0 C. Furthermore, Li-S pouch/beaker batteries with a POM-based cathode were successfully demonstrated. This work provides essential inputs to promote molecular catalyst design and its application in LSBs.
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http://dx.doi.org/10.1021/acsnano.1c03852DOI Listing
June 2021

Simulating spatial change of mangrove habitat under the impact of coastal land use: Coupling MaxEnt and Dyna-CLUE models.

Sci Total Environ 2021 Sep 21;788:147914. Epub 2021 May 21.

Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, PR China; Fujian Provincial Key Laboratory of Marine Ecological Conservation and Restoration, Xiamen 361005, PR China. Electronic address:

Global mangrove forests have exhibited distinct changes in the past decades owing to anthropogenic activities, with land-use pressure being among the main causes of mangrove loss. Thus, understanding the inherent conflicts between conservation/restoration and land-use demands is fundamental for mangrove management. To predict how land-use changes will drive the spatiotemporal patterns of mangrove habitats, a novel integrated framework coupling MaxEnt and Dyna-CLUE modeling was proposed. The coupled model can identify suitable mangrove afforestation habitats and predict the impact of land-use change on potential mangrove habitats. In this study, the model was used to predict the mangrove habitat change in 2030 in the province with the most mangrove forests in China. The potential suitable habitat of 14 mangrove species under three coastal land-use scenarios were mapped using the coupled model. Under the current trend scenario, only 41.2% of the existing wetland would be retained, whereas the potential distribution area of all the mangrove species will decrease by an average of 30%. Under the sustainable development and ecological protection scenarios, the mangrove habitat could be increased by 11% to 61%, depending on the species. Different mangrove species showed varied sensitivity to the improved land-use policies, with several species being harder to restore than others, even under aggressive protection and restoration policies. The combined use of both MaxEnt and Dyna-CLUE models proved complementary and offered insights into the impacts of different land-use policies on the spatiotemporal change of mangrove habitats.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147914DOI Listing
September 2021

Synthesis and Characterization of Methacrylate-Functionalized Betulin Derivatives as Antibacterial Comonomer for Dental Restorative Resins.

ACS Biomater Sci Eng 2021 07 11;7(7):3132-3140. Epub 2021 Jun 11.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.

Secondary caries is the primary cause of composite restoration failures, resulting from marginal leakage and bacterial accumulation in the oral environment. Antibacterial dental composites, especially antibacterial monomers, have emerged as a promising strategy to inhibit secondary caries, which is pivotal to prolonging the lifespan of dental restorations. In this work, monomethacrylate- and dimethacrylate-functionalized betulin derivatives (MBet and MBet) were synthesized via an esterification reaction and served as antibacterial comonomers to develop novel dental resin formulations, in which MBet and MBet were incorporated to partially or completely replace bisphenol A glycerolate dimethacrylate (Bis-GMA). The control resin was a mixture based on Bis-GMA and tri(ethyleneglycol) dimethacrylate (TEGDMA) with a weight ratio of 50:50 (5B5T). The effect of the resin compositions and the chemical structures of MBet and MBet on the rheology behavior, optical property, polymerization kinetics, mechanical performance, cell viability, and antibacterial activity of dental resins were systematically investigated. Among all materials, the 1MBet4B5T resin with 10 wt % substitution of Bis-GMA by MBet exhibited comparable viscosity, higher light transmittance, improved degree of conversion, and mechanical properties compared with 5B5T. After incubation for 24 h, this optimal resin also possessed the best antibacterial activity against , which had a significantly lower bacterial concentration (1.53 × 10 CFU/mL) than 5B5T (9.03 × 10 CFU/mL). Introducing betulin-based comonomers into dental resins is a potential strategy to develop antibacterial dental materials without sacrificing physical-mechanical properties.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00563DOI Listing
July 2021

Enhancement of Time Resolution in Ultrasonic time-of-flight Diffraction Technique with Frequency Domain Sparsity-Decomposability Inversion (FDSDI) Method.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Jun 9;PP. Epub 2021 Jun 9.

The lack of time resolution restricts the quantitative detection of shallow subsurface defects with ultrasonic time-of-flight diffraction (TOFD) technique due to the superposition between lateral wave and diffracted waves from upper and lower tips. In this paper, frequency domain sparsity-decomposability inversion (FDSDI) method was proposed to enhance the time resolution in TOFD based on the sparsity and decomposability of ultrasonic reflection sequence. An optimization problem was formulated in frequency domain by combining l1 and l2 norm constraints. The simulation was performed with a carbon steel model containing a series of shallow subsurface cracks at the depths of 2.0 mm, 2.5 mm, 3.0 mm, 3.5 mm, and 4.0 mm. The relative measurement errors of defect depths and heights were no more than 6.57%, and the depth of dead zone was reduced by 70%. Subsequently, the feasibility of FDSDI method was experimentally verified on a carbon steel specimen with an artificial defect. The defect depth and height were calculated with relative errors within 6.0%. Finally, the detection capacity of FDSDI method was discussed, and the effects of frequency bandwidth, regularization parameter, and noise on inversion results were analyzed by experiments. It is concluded that the FDSDI method decouples the multiple overlapped signals and significantly improves the time resolution to quantify the small defects in dead zone.
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http://dx.doi.org/10.1109/TUFFC.2021.3087754DOI Listing
June 2021

Decitabine Sensitizes the Radioresistant Lung Adenocarcinoma to Pemetrexed Through Upregulation of Folate Receptor Alpha.

Front Oncol 2021 17;11:668798. Epub 2021 May 17.

Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, China.

Chemotherapy is the backbone of subsequent treatment for patients with lung adenocarcinoma (LUAD) exhibiting radiation resistance, and pemetrexed plays a critical role in this chemotherapy. However, few studies have assessed changes in the sensitivity of LUAD cells to pemetrexed under radioresistant circumstances. Therefore, the objectives of this study were to delineate changes in the sensitivity of radioresistant LUAD cells to pemetrexed and to elucidate the related mechanisms and then develop an optimal strategy to improve the cytotoxicity of pemetrexed in radioresistant LUAD cells. Our study showed a much lower efficacy of pemetrexed in radioresistant cells than in parental cells, and the mechanism of action was the significant downregulation of folate receptor alpha (FRα) by long-term fractionated radiotherapy, which resulted in less cellular pemetrexed accumulation. Interestingly, decitabine effectively reversed the decrease in FRα expression in radioresistant cells through an indirect regulatory approach. Thereafter, we designed a combination therapy of pemetrexed and decitabine and showed that the activation of FRα by decitabine sensitizes radioresistant LUAD cells to pemetrexed both and in xenografts. Our findings raised a question regarding the administration of pemetrexed to patients with LUAD exhibiting acquired radioresistance and accordingly suggested that a combination of pemetrexed and decitabine would be a promising treatment strategy.
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http://dx.doi.org/10.3389/fonc.2021.668798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165306PMC
May 2021

Alteration and dysfunction of ion channels/transporters in a hypoxic microenvironment results in the development and progression of gastric cancer.

Cell Oncol (Dordr) 2021 Apr 15. Epub 2021 Apr 15.

Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou Province, China.

Background: Gastric cancer (GC) is one of the most common malignant cancers in the world and has only few treatment options and, concomitantly, a poor prognosis. It is generally accepted now that the tumor microenvironment, particularly that under hypoxia, plays an important role in cancer development. Hypoxia can regulate the energy metabolism and malignancy of tumor cells by inducing or altering various important factors, such as oxidative stress, reactive oxygen species (ROS), hypoxia-inducible factors (HIFs), autophagy and acidosis. In addition, altered expression and/or dysfunction of ion channels/transporters (ICTs) have been encountered in a variety of human tumors, including GC, and to play an important role in the processes of tumor cell proliferation, migration, invasion and apoptosis. Increasing evidence indicates that ICTs are at least partly involved in interactions between cancer cells and their hypoxic microenvironment. Here, we provide an overview of the different ICTs that regulate or are regulated by hypoxia in GC.

Conclusions And Perspectives: Hypoxia is one of the major obstacles to cancer therapy. Regulating cellular responses and factors under hypoxia can inhibit GC. Similarly, altering the expression or activity of ICTs, such as the application of ion channel inhibitors, can slow down the growth and/or migration of GC cells. Since targeting the hypoxic microenvironment and/or ICTs may be a promising strategy for the treatment of GC, more attention should be paid to the interplay between ICTs and the development and progression of GC in such a microenvironment.
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http://dx.doi.org/10.1007/s13402-021-00604-1DOI Listing
April 2021

Smart configuration of cobalt hexacyanoferrate assembled on carbon fiber cloths for fast aqueous flexible sodium ion pseudocapacitor.

J Colloid Interface Sci 2021 Jul 17;594:522-530. Epub 2021 Mar 17.

Institute of Materials for Energy and Environment, and College of Materials Science and Engineering, Qingdao University, China. Electronic address:

Aqueous rechargeable batteries (ARBs) have the advantages of low cost, high safety and sustainable environmental friendliness. However, the key challenge for ARBs is the narrow electrochemical stability window of the water, undoubtedly leading to the low output voltage, the underachieved capacity and a low energy density. Prussian blues and their analogues have attracted great research interest for energy storage due to the advantages of facile synthesis, versatile categories and tunable three dimensional frameworks. Herein a flexible integrated potassium cobalt hexacyano ferrates (Co-HCF) on carbon fiber clothes (CFCs) were designed through a feasible route combining the controllable electrochemical deposition and the efficient co-precipitation process. The [email protected] demonstrate an excellent sodium ion storage with a high reversible capacity of 91 mAh g at 1 A g and 55 mAh g at 10 A g in aqueous electrolytes. The long cycling stability at the high current demonstrate the excellent structure stability of the [email protected] Analysis on the rate Cyclic voltammograms (CV) profiles reveal the fast electrochemical kinetics with the capacitive controlled process, while galvanostatic intermittent titration technique (GITT) tests fast diffusion coefficient related with the sodium ions intercalation/deintercalation in the [email protected] In addition, the flexible [email protected] also demonstrate excellent performance for quasi-solid-state ARBs even at the high bending angles. The high quality [email protected] with advantage of high rate capability and excellent reversible capacity make them a promising candidate for high performance ARBs.
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http://dx.doi.org/10.1016/j.jcis.2021.03.031DOI Listing
July 2021

Effect of pyrethroid pesticides on the testis of male rats: A meta-analysis.

Toxicol Ind Health 2021 Apr 16;37(4):229-239. Epub 2021 Mar 16.

Department of Neonatology, Maternal and Child health Hospital, 372527Weifang Medical University, Weifang, China.

This study quantitatively evaluated the effects of pyrethroid pesticides on the testis of male rats. An extensive literature search for relevant studies was conducted on PubMed, Web of Science, Excerpta Medica Database, the Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database. Pooled standard mean difference with corresponding 95% confidence interval was calculated via the random-effects model. was used to evaluate heterogeneity among studies. A total of 19 studies were included for analysis in our study. Results indicated that the sperm count of rats exposed to fenvalerate was lower than that of rats in control groups. The sperm count, sperm motility, and testosterone level of rats exposed to cypermethrin and deltamethrin were lower than those of rats in control groups. Moreover, the sperm morphology of rats exposed to these pyrethroid pesticides was abnormal compared with that of rats in control groups. The present meta-analysis indicates that pyrethroid pesticides decrease rat sperm count, sperm motility, and testosterone level and cause abnormal rat sperm morphology. Therefore, pyrethroid pesticides can damage the testis of male rats.
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http://dx.doi.org/10.1177/07482337211000979DOI Listing
April 2021

Microbial Functional Responses Explain Alpine Soil Carbon Fluxes under Future Climate Scenarios.

mBio 2021 02 23;12(1). Epub 2021 Feb 23.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing, China

Soil microorganisms are sensitive to temperature in cold ecosystems, but it remains unclear how microbial responses are modulated by other important climate drivers, such as precipitation changes. Here, we examine the effects of six warming and/or precipitation treatments in alpine grasslands on microbial communities, plants, and soil carbon fluxes. These treatments differentially affected soil carbon fluxes, gross primary production, and microbial communities. Variations of soil CO and CH fluxes across all sites significantly (>0.70, < 0.050) correlated with relevant microbial functional abundances but not bacterial or fungal abundances. Given tight linkages between microbial functional traits and ecosystem functionality, we conclude that future soil carbon fluxes in alpine grasslands can be predicted by microbial carbon-degrading capacities. The warming pace in the Tibetan Plateau, which is predominantly occupied by grassland ecosystems, has been 0.2°C per decade in recent years, dwarfing the rate of global warming by a factor of 2. Many Earth system models project substantial carbon sequestration in Tibet, which has been observed. Here, we analyzed microbial communities under projected climate changes by 2100. As the soil "carbon pump," the growth and activity of microorganisms can largely influence soil carbon dynamics. However, microbial gene response to future climate scenarios is still obscure. We showed that the abundances of microbial functional genes, but not microbial taxonomy, were correlated with carbon fluxes and ecosystem multifunctionality. By identifying microbial traits linking to ecosystem functioning, our results can guide the assessment of future soil carbon fluxes in alpine grasslands, a critical step toward mitigating climate changes.
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http://dx.doi.org/10.1128/mBio.00761-20DOI Listing
February 2021

Efficacy of L-Carnitine for Dilated Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

Biomed Res Int 2021 12;2021:9491615. Epub 2021 Jan 12.

Department of Pharmacy, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.

Background: L-carnitine mediates the utilization of fatty acids and glucose in the myocardium. The potential of L-carnitine in managing dilated cardiomyopathy (DCM) in patients has been extensively reported, with additional benefits.

Objective: This meta-analysis purposed to explore the clinical efficacy of L-carnitine therapy on DCM patients.

Methods: We searched publications up to May 2020 from several databases including PubMed, Embase, Cochrane Library, Chinese Biomedical (CBM) database, Chinese Science and Technology Periodicals database (VIP), Chinese National Knowledge Infrastructure (CNKI) database, and Wanfang database. Subsequently, publications that met the inclusion criteria were systematically evaluated by two independent reviewers.

Results: A total of 23 RCTs conducted in China with 1455 DCM patients were included in this study. In the meta-analysis, L-carnitine therapy was associated with a considerable improvement in the overall efficacy (RR = 1.28, 95% CI (1.21-1.36), < 0.0001), left ventricular ejection fraction (LVEF) (MD = 6.16%, 95% CI (4.50, 7.83), < 0.0001), and cardiac output (CO) (MD = 0.88 L/min, 95% CI (0.51, 1.25), < 0.0001) as compared to the control group. Moreover, L-carnitine therapy significantly decreased left ventricular end-diastolic dimension (LVEDD) (MD = -2.53, 95% CI (-3.95, -1.12), = 0.0005), brain natriuretic peptide (BNP) (SMD = -1.71 ng/L, 95% CI (-3.02, -0.40), = 0.01), and the transforming growth factor-beta (TGF-1) (MD = -56.78 ng/L, 95% CI (-66.02, -47.53), < 0.0001).

Conclusions: L-carnitine potentially enhanced the therapeutic efficiency in DCM patients. Following weaknesses in the evidence due to low methodological quality and high clinical heterogeneity in the included studies, well-designed trials are recommended.
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http://dx.doi.org/10.1155/2021/9491615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817303PMC
February 2021

Preparation of [email protected] and Solvent Inducing Enhancement Strategy for Raman Determination of Salivary Thiocyanate.

ACS Appl Mater Interfaces 2021 Feb 27;13(5):5966-5974. Epub 2021 Jan 27.

The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, and Department of Chemistry, Shanghai Normal University, Shanghai 200234, P. R. China.

Making the substrates form highly dense, homogeneous, and stable hotspots regions is important for the sensitive detection of surface-enhanced Raman spectroscopy (SERS). A new strategy based on solvent-induced (SI) SERS substrate to form a stable interval of the hotspot for detection was explored and the enhancement factor (EF) of our SERS substrates could reach about 1.4 × 10. By preferential adsorption of alcohol solutions by Q-Sepharose microsphere (QSS) in mixed water and alcohol solutions, the size of [email protected] was dynamically adjusted and the spacing between gold nanoparticles (AuNPs) was adjusted to keep the substrate in the optimal hotspot mode for the sensitive detection of SERS in the liquid state. As a real application case, such a SI-SERS strategy was employed to determine SCN in saliva and a limit of detection (LOD) of about 10 M could be achieved.
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http://dx.doi.org/10.1021/acsami.0c19650DOI Listing
February 2021

Targeted overexpression of PPARγ in skeletal muscle by random insertion and CRISPR/Cas9 transgenic pig cloning enhances oxidative fiber formation and intramuscular fat deposition.

FASEB J 2021 02;35(2):e21308

Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs & Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, P.R. China.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator of adipogenesis and lipogenesis. To understand its roles in fiber formation and fat deposition in skeletal muscle, we successfully generated muscle-specific overexpression of PPARγ in two pig models by random insertion and CRISPR/Cas9 transgenic cloning procedures. The content of intramuscular fat was significantly increased in PPARγ pigs while had no changes on lean meat ratio. PPARγ could promote adipocyte differentiation by activating adipocyte differentiating regulators such as FABP4 and CCAAT/enhancer-binding protein (C/EBP), along with enhanced expression of LPL, FABP4, and PLIN1 to proceed fat deposition. Proteomics analyses demonstrated that oxidative metabolism of fatty acids and respiratory chain were activated in PPARγ pigs, thus, gathered more Ca in PPARγ pigs. Raising of Ca could result in increased phosphorylation of CAMKII and p38 MAPK in PPARγ pigs, which can stimulate MEF2 and PGC1α to affect fiber type and oxidative capacity. These results support that skeletal muscle-specific overexpression of PPARγ can promote oxidative fiber formation and intramuscular fat deposition in pigs.
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http://dx.doi.org/10.1096/fj.202001812RRDOI Listing
February 2021

Noncanonical scaffolding of G and β-arrestin by G protein-coupled receptors.

Science 2021 03 21;371(6534). Epub 2021 Jan 21.

Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific G protein subtypes and β-arrestin adaptor proteins. G protein-mediated signaling and β-arrestin-mediated signaling have been considered separable. We show here that GPCRs promote a direct interaction between G protein subtype family members and β-arrestins regardless of their canonical G protein subtype coupling. G:β-arrestin complexes bound extracellular signal-regulated kinase (ERK), and their disruption impaired both ERK activation and cell migration, which is consistent with β-arrestins requiring a functional interaction with G for certain signaling events. These results introduce a GPCR signaling mechanism distinct from canonical G protein activation in which GPCRs cause the formation of G:β-arrestin signaling complexes.
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http://dx.doi.org/10.1126/science.aay1833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005335PMC
March 2021

Downregulation of breast cancer resistance protein by long-term fractionated radiotherapy sensitizes lung adenocarcinoma to SN-38.

Invest New Drugs 2021 Apr 21;39(2):458-468. Epub 2021 Jan 21.

Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.

Chemotherapy is usually the subsequent treatment for non-small cell lung cancer patients with acquired radioresistance after long-term fractionated radiotherapy. However, few studies have focused on the selection of chemotherapeutic drugs to treat lung adenocarcinoma patients with radioresistance. Our study compared the sensitivity changes of lung adenocarcinoma cells to conventional chemotherapeutic drugs under radioresistant circumstances by using three lung adenocarcinoma cell models, which were irradiated with fractionated X-rays at a total dose of 60 Gy. The results showed that the toxicities of paclitaxel, docetaxel and SN-38 were increased in radioresistant cells. The IC values of docetaxel and SN-38 decreased 0 ~ 3 times and 3 ~ 36 times in radioresistant cells, respectively. Notably, the A549 radioresistant cells were approximately 36 times more sensitive to SN-38 than the parental cells. Further results revealed that the downregulation of the efflux transporter BCRP by long-term fractionated irradiation was an important factor contributing to the increased cytotoxicity of SN-38. In addition, the reported miRNAs and transcriptional factors that regulate BCRP did not participate in the downregulation. In conclusion, these results presented important data on the sensitivity changes of lung adenocarcinoma cells to chemotherapeutic drugs after acquiring radioresistance and suggested that irinotecan (the prodrug of SN-38) might be a promising drug candidate for lung adenocarcinoma patients with acquired radioresistance.
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http://dx.doi.org/10.1007/s10637-020-01003-3DOI Listing
April 2021

Physiological and Pathophysiological Roles of Ion Transporter-Mediated Metabolism in the Thyroid Gland and in Thyroid Cancer.

Onco Targets Ther 2020 3;13:12427-12441. Epub 2020 Dec 3.

Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, People's Republic of China.

Thyroid cancer is the most common type of endocrine tumor and has shown an increasing annual incidence, especially among women. Patients with thyroid cancer have a good prognosis, with a high five-year survival rate; however, the recurrence rate and disease status of thyroid cancer remain a burden for patients, which compels us to further elucidate the pathogenesis of this disease. Recently, ion transporters have gradually become a hot topic in the field of thyroid gland biology and cancer research. Additionally, alterations in the metabolic state of tumor cells and protein molecules have gradually become the focus of scientific research. This review focuses on the progress in understanding the physiological and pathophysiological roles of ion transporter-mediated metabolism in both the thyroid gland and thyroid cancer. We also hope to shed light on new targets for the treatment and prognosis of thyroid cancer.
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http://dx.doi.org/10.2147/OTT.S280797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721308PMC
December 2020

From electronic health records to terminology base: A novel knowledge base enrichment approach.

J Biomed Inform 2021 01 21;113:103628. Epub 2020 Nov 21.

School of Information Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.

Enriching terminology base (TB) is an important and continuous process, since formal term can be renamed and new term alias emerges all the time. As a potential supplementary for TB enrichment, electronic health record (EHR) is a fundamental source for clinical research and practise. The task to align the set of external terms in EHRs to TB can be regarded as entity alignment without structure information. Conventional approaches mainly use internal structural information of multiple knowledge bases (KBs) to map entities and their counterparts among KBs. However, the external terms in EHRs are independent clinical terms, which lack of interrelations. To achieve entity alignment in this case, we proposed a novel automatic TB enrichment approach, named semantic & structure embeddings-based relevancy prediction (S2ERP). To obtain the semantic embedding of external terms, we fed them with formal entity into a pre-trained language model. Meanwhile, a graph convolutional network was used to obtain the structure embeddings of the synonyms and hyponyms in TB. Afterwards, S2ERP combines both embeddings to measure the relevancy. Experimental results on clinical indicator TB, collected from 38 top-class hospitals of Shanghai Hospital Development Center, showed that the proposed approach outperforms baseline methods by 14.16% in [email protected]
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http://dx.doi.org/10.1016/j.jbi.2020.103628DOI Listing
January 2021

Downregulation of glucose-6-phosphatase expression contributes to fluoxetine-induced hepatic steatosis.

J Appl Toxicol 2021 Aug 12;41(8):1232-1240. Epub 2020 Nov 12.

Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Fluoxetine is a first-line selective serotonin reuptake inhibitor widely applied for the treatment of depression; however, it induces abnormal hepatic lipid metabolism. Considering decreased expression or function of glucose-6-phosphatase (G6Pase), a key enzyme in gluconeogenesis, or the upregulation of fatty acid uptake, causes hepatic lipid accumulation. The aim of this study was to elucidate whether G6Pase regulation and fatty acid uptake alteration contribute to fluoxetine-induced abnormal hepatic lipid metabolism. Our study revealed that 8-week oral administration of fluoxetine dose-dependently increased hepatic triglyceride, causing hepatic steatosis. Concomitantly, the expression of G6Pase in mouse livers and primary mouse hepatocytes (PMHs) was downregulated in a concentration-dependent manner. Furthermore, fluoxetine increased the concentrations of glucose-6-phosphate (G6Pase substrate) and acetyl CoA (the substrate for de novo lipogenesis) in mouse livers. Additionally, fluoxetine also induced lipid accumulation and downregulated G6Pase expression in HepG2 cells. However, the uptake of green fluorescent fatty acid (BODIPY™ FL C16) in PMHs was not changed after fluoxetine treatment, indicating that fluoxetine-induced hepatic steatosis was not associated with fatty acid uptake alteration. In conclusion, fluoxetine downregulated hepatic G6Pase expression, subsequently enhanced the transformation of glucose to lipid, and ultimately resulted in hepatic steatosis, but with no impact on fatty acid uptake.
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http://dx.doi.org/10.1002/jat.4109DOI Listing
August 2021

Application of carbon nanoparticles combined with intraoperative neuromonitoring in papillary thyroid microcarcinoma surgery.

Am J Otolaryngol 2021 Jan - Feb;42(1):102790. Epub 2020 Oct 24.

Gastroenterology Department, Affiliated Hospital of Zunyi Medical University, Zunyi, China. Electronic address:

Purposes: To improve the lymph node dissection as well as protect parathyroid gland and recurrent laryngeal nerve, the carbon nanoparticles and intraoperative neuromonitoring were applied in papillary thyroid microcarcinoma surgery.

Methods: Carbon nanoparticles and intraoperative neuromonitoring were used in the experimental group, whereas the control group were not. Routine pathological examination was performed.

Results: The lymph nodes dissected was significantly higher in the experimental group, but the metastatic lymph nodes were not. The number of mistakenly dissected parathyroid gland and postoperative hypoparathyroidism were 3 and 13 in the experimental group respectively, significantly less than 10 and 25 in the control group. The incidences of overall, transient and persistent recurrent laryngeal nerve palsy in the experimental group were 5.5%, 5.5% and 0% respectively, whereas in the control group were 8.6%, 6.9% and 1.7%.

Conclusions: Carbon nanoparticles can improve lymph node dissection in papillary thyroid microcarcinoma surgery, and the combination of carbon nanoparticles with intraoperative neuromonitoring can reduce surgical complications and improve patient quality of life.
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http://dx.doi.org/10.1016/j.amjoto.2020.102790DOI Listing
April 2021

A mechanistic effect modeling approach to the prioritization of hidden drivers in chemical cocktails.

Sci Total Environ 2020 Dec 24;748:142525. Epub 2020 Sep 24.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China. Electronic address:

Exposure to a single chemical does not exist in reality. Mixtures, which are the ecological norm, are often characterized by numerous intrinsic driving factors with unknown combined effects. Interactions between heterogeneous chemicals, or chemical and nonchemical stressors, could alter their toxicity traits relative to single exposure. Hence, revealing the hidden environmental effects affecting multiple stressor interactions is essential to expand our knowledge about uncertainty sources in chemical risk-based decision contexts. Global sensitivity analysis (GSA) techniques involving Morris method sampling and elementary effects (EE) sensitivity analysis was applied to investigate the driving factors underlying the combined effects on Scenedesmus obliquus, and identify the mode of interaction in mixtures at environmentally-relevant concentrations. One hundred mixed-exposure formulas were generated with 9 variables (8 chemicals and temperature) via the Morris method, representing environmental perspective in the field. Subsequently, EE sensitivity analysis combined with quantitative high-throughput screening (q-HTS) was adopted to identify the most critical mixture and its primary drivers. Combined exposure exerted significantly increased effects on S. obliquus compared to the effects of individual exposure. The critical drivers were identified and validated by the control variate method. For the mode of combined action, mixture toxicity did not match the additivity relationship, and a strong interaction existed among chemicals. Collectively, the data provides evidence that a combination of specific pesticides and emerging brominated flame retardants can produce comparable, or even stronger, bionegative effects than pure chemicals due to complicated interactions. The method used offers direct comparison of multifarious factors in a unified standard scale, bridges the actual interaction scenarios in the field to toxicity simulations in the laboratory, and fill a gap in ecotoxicology.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142525DOI Listing
December 2020

Mapping the potential of mangrove forest restoration based on species distribution models: A case study in China.

Sci Total Environ 2020 Dec 12;748:142321. Epub 2020 Sep 12.

Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, PR China; Fujian Provincial Key Laboratory of Marine Ecological Conservation and Restoration, Xiamen 361005, PR China. Electronic address:

Mangrove forests support numerous ecosystem services and contribute to coastal ecological risk reduction. However, they are one of the most severely threatened ecosystems in the world. China has carried out national mangrove restoration projects, but there is still insufficient scientific information for the strategic planning of this restoration. In this study, we carried out mangrove suitability assessments using the genetic algorithm for rule-set prediction (GARP) and maximum entropy (MaxEnt) models, and we mapped the restoration potential of mangrove forests in China for the first time. The restoration potential index (RPI), which combines suitability and land use data, is proposed as a rapid estimator method for locating theoretically available areas for restoration. The results showed that the MaxEnt model performed better than GARP in predicting potential mangrove distributions. Temperature was the most important environmental factor for determining large scale distribution of mangroves. The predicted northern limit of mangrove distribution was around 28°27' N-28°35' N. Using the RPI approach, 16,800 ha with the potential to restore mangrove forests was identified. According to both models, the largest area with restoration potential occurs along the Guangdong and Guangxi coast. Nationwide, about 75% of the potential area suitable for mangrove forests has been lost as a consequence of land use and is no longer available for restoration. Around 6400 ha of ponds is currently used for aquaculture, accounting for 38% of theoretically restorable areas. These areas can be a priority for mangrove forest restoration. In conclusion, our findings provide a better scientific understanding of mangrove distribution in China and can underpin strategic design and planning of mangrove restoration.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142321DOI Listing
December 2020

Phase Behavior and Thermo-Mechanical Properties of IF-WS Reinforced PP-PET Blend-Based Nanocomposites.

Polymers (Basel) 2020 Oct 13;12(10). Epub 2020 Oct 13.

College of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.

The industrial advancement of high-performance technologies directly depends on the thermo-mechanical properties of materials. Here we give an account of a facile approach for the bulk production of a polyethylene terephthalate (PET)/polypropylene (PP)-based nanocomposite blend with Inorganic Fullerene Tungsten Sulfide (IF-WS) nanofiller using a single extruder. Nanofiller IF-WS was produced by the rotary chemical vapor deposition (RCVD) method. Subsequently, IF-WS nanoparticles were dispersed in PET and PP in different loadings to access impact and their dispersion behavior in polymer matrices. As-prepared blend nanocomposites were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), dynamic differential scanning (DSC), dynamic mechanical analysis (DMA), and X-ray diffraction (XRD). In this work, the tensile strength of the PP/PET matrix with 1% IF-WS increased by 31.8%, and the thermal stability of the sample PP/PET matrix with 2% increased by 18 °C. There was an extraordinary decrease in weight loss at elevated temperature for the nanocomposites in TGA analysis, which confirms the role of IF-WS on thermal stability versus plain nanocomposites. In addition, this method can also be used for the large-scale production of such materials used in high-temperature environments.
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http://dx.doi.org/10.3390/polym12102342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602003PMC
October 2020

Fabrication of homogeneous waffle-like silver composite substrate for Raman determination of trace chloramphenicol.

Mikrochim Acta 2020 Oct 7;187(11):593. Epub 2020 Oct 7.

Department of Chemistry, Key Laboratory of Resource Chemistry of Ministry of Education, 100 Guilin Road, Shanghai, 200234, People's Republic of China.

Waffle-like anodized aluminum oxide homogeneously immobilized with Ag nanoparticles (AAO/Ag) is rationally designed and fabricated as surface-enhanced Raman scattering (SERS) substrate. The as-prepared SERS substrate is characterized with transmission electron microscope (TEM), scanning electron microscopy (SEM), UV-Vis spectrophotometer, and Fourier transform infrared spectrometer (FT-IR). The AAO/Ag substrate shows good uniformity of the Raman signals (RSD = 7.02%) due to waffle-like AAO supporting the well-dispersed Ag nanoparticles. For real application, the AAO/Ag substrate is used for rapid determination of chloramphenicol (CAP) in honey with low detection limit (4.0 × 10 mol L) and good linearity from 1.0 × 10 to 1.0 × 10 mol L based on the SERS peak at 1348 cm. The better accumulation in the short pore path of AAO improves the target molecule approaching into the vicinity of hot spots of Ag nanoparticles. The high selectivity for CAP is attributed to the strong interaction between -NO group in CAP and the composite substrate. Schematic representation of the preparation of SERS substrate, AAO/Ag-5 composite nanoparticles, and antibiotic determination.
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http://dx.doi.org/10.1007/s00604-020-04567-2DOI Listing
October 2020

Determination of intracellular anlotinib, osimertinib, afatinib and gefitinib accumulations in human brain microvascular endothelial cells by liquid chromatography/tandem mass spectrometry.

Rapid Commun Mass Spectrom 2021 Jan;35(1):e8955

Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China.

Rationale: Brain metastases are a common complication in patients with non-small-cell lung cancer (NSCLC). Anlotinib hydrochloride is a novel multi-target tyrosine kinase inhibitor (TKI) exhibiting a superior overall response rate for brain metastases from NSCLC. The penetrability of anlotinib and three generations of epidermal growth factor receptor (EGFR) TKIs (osimertinib, afatinib and gefitinib) into brain microvascular endothelial cells (HBMECs) was compared.

Methods: A sensitive quantification method for the four TKIs was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). Anlotinib and the three EGFR TKIs were separated on an ACQUITY BEH C18 column after a direct protein precipitation, and then analyzed using electrospray ionization in positive ion mode. The linearity, accuracy, precision, limit of quantification, specificity and stability were assessed.

Results: The four analytes could be efficiently quantified in a single run of 3.8 min. The validation parameters of all analytes satisfy the acceptance criteria of bioanalytical method guidelines. The calibration range was 0.2-200 ng mL for anlotinib and gefitinib, 1-500 ng mL for osimertinib and 1-200 ng mL for afatinib. The penetration of anlotinib across HBMECs was comparable with that of afatinib and gefitinib but less than that of osimertinib.

Conclusions: A sensitive LC/MS/MS method to simultaneously measure anlotinib, osimertinib, afatinib and gefitinib in cell extracts was successfully validated and applied to determine their uptake inside HBMECs, which could pave the way for future research on the role of anlotinib in NSCLC brain metastases.
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http://dx.doi.org/10.1002/rcm.8955DOI Listing
January 2021

extract (FA-2-b-β) induces apoptosis in chronic myeloid leukemia cells.

Oncol Lett 2020 Nov 21;20(5):270. Epub 2020 Sep 21.

Department of Hematology, Gansu Provincial Hospital, Lanzhou, Gansu 730000, P.R. China.

(AbM) is a mushroom belonging to the Basidiomycetes family, which is believed to have antitumor and antioxidative activities. Proteoglycans and ergosterol are considered the key compounds of AbM for antitumor properties and so are used in complementary and alternative medicine as an anticancer drug. AbM is used to avoid serious side effects that would inevitably affect patients. Currently, the efficacy of AbM against chronic myeloid leukemia (CML) has not been established. The present study aimed to investigate the antitumor activities of the acidic RNA protein complex, FA-2-b-β, extracted from wild edible AbM. The CML K562 cells or primary CML bone marrow (BM) cells were treated with FA-2-b-β at different concentrations and time points. CML cell line proliferation and apoptosis were determined using the CCK-8 assay or Annexin V/propidium iodide (PI) labeling, RT-qPCR and western blotting was performed to determine the involvement of the Wnt/β-catenin-associated apoptotic pathway. The results of the present study demonstrated that FA-2-b-β has a high anti-proliferative potency and strong pro-apoptotic effects. Thus, daily intake of mushrooms containing FA-2-b-β may be an adequate source as an alternative medicine in the management of CML, and may provide useful information for the development of a novel therapeutic target in this area.
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http://dx.doi.org/10.3892/ol.2020.12133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517625PMC
November 2020

Proteome-wide effects of naphthalene-derived secondary organic aerosol in BEAS-2B cells are caused by short-lived unsaturated carbonyls.

Proc Natl Acad Sci U S A 2020 10 28;117(41):25386-25395. Epub 2020 Sep 28.

Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada;

Exposure to air pollution causes adverse health outcomes, but the toxicity mechanisms remain unclear. Here, we investigated the dynamic toxicities of naphthalene-derived secondary organic aerosol (NSOA) in a human bronchial epithelial cell line (BEAS-2B) and identified the chemical components responsible for toxicities. The chemical composition of NSOA was found to vary with six simulated atmospheric aging conditions (C-C), as characterized by high-resolution mass spectrometry and ion mobility mass spectrometry. Global proteome profiling reveals dynamic evolution in toxicity: Stronger proteome-wide impacts were detected in fresh NSOA, but the effects declined along with atmospheric aging. While Nrf2-regulated proteins (e.g., ) were significantly up-regulated, the majority (78 to 97%) of proteins from inflammation and other pathways were down-regulated by NSOA exposure (e.g., ). This pattern is distinct from the reactive oxygen species (ROS)-mediated toxicity pathway, and an alternative cysteine reaction pathway was revealed by the decreased abundance of proteins (e.g., ) prone to posttranslational thiol modification. This pathway was further validated by observing decreased Nrf2 response in reporter cells, after preincubating NSOA with cysteine. Ethynyl-naphthalene probe was employed to confirm the alkylation of cellular proteome thiols on the proteome-wide level by fresh NSOA via in-gel fluorescence imaging. Nontarget analysis identified several unsaturated carbonyls, including naphthoquinones and hydroxylated naphthoquinones, as the toxic components responsible for cysteine reactivity. Our study provides insights into the dynamic toxicities of NSOA during atmospheric aging and identifies short-lived unsaturated carbonyls as the predominant toxic components at the posttranslational level.
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http://dx.doi.org/10.1073/pnas.2001378117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568281PMC
October 2020

Heteropoly acid-driven assembly of glutathione into redox-responsive underwater adhesive.

Chem Commun (Camb) 2020 Sep 18;56(75):11034-11037. Epub 2020 Aug 18.

State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Qianjin Avenue 2699, Changchun 130012, China.

Dynamic adhesives were fabricated based on the ionic co-assembly of glutathione and heteropoly acids (HPAs). The underwater attachment and detachment of the adhesives were achieved based on the redox properties of glutathione. We demonstrated that the formation of disulfide bonds of glutathione plays a pivotal role in the formation of robust 3D network structures as well as the improvement of cohesion.
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http://dx.doi.org/10.1039/d0cc03746jDOI Listing
September 2020

Pathological role of ion channels and transporters in the development and progression of triple-negative breast cancer.

Cancer Cell Int 2020 6;20:377. Epub 2020 Aug 6.

Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003 Guizhou Province China.

Breast cancer is a common malignancy in women. Among breast cancer types, triple-negative breast cancer (TNBC) tends to affect younger women, is prone to axillary lymph node, lung, and bone metastases; and has a high recurrence rate. Due to a lack of classic biomarkers, the currently available treatments are surgery and chemotherapy; no targeted standard treatment options are available. Therefore, it is urgent to find a novel and effective therapeutic target. As alteration of ion channels and transporters in normal mammary cells may affect cell growth, resulting in the development and progression of TNBC, ion channels and transporters may be promising new therapeutic targets for TNBC. This review summarizes ion channels and transporters related to TNBC and may provide new tumor biomarkers and help in the development of novel targeted therapies.
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http://dx.doi.org/10.1186/s12935-020-01464-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409684PMC
August 2020
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