Publications by authors named "Guoying Zhang"

164 Publications

The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability.

Mol Cell 2021 Apr 22. Epub 2021 Apr 22.

CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Electronic address:

Cholesterol metabolism is tightly associated with colorectal cancer (CRC). Nevertheless, the clinical benefit of statins, the inhibitor of cholesterol biogenesis mevalonate (MVA) pathway, is inconclusive, possibly because of a lack of patient stratification criteria. Here, we describe that YAP-mediated zinc finger MYND-type containing 8 (ZMYND8) expression sensitizes intestinal tumors to the inhibition of the MVA pathway. We show that the oncogenic activity of YAP relies largely on ZMYND8 to enhance intracellular de novo cholesterol biogenesis. Disruption of the ZMYND8-dependent MVA pathway greatly restricts the self-renewal capacity of Lgr5 intestinal stem cells (ISCs) and intestinal tumorigenesis. Mechanistically, ZMYND8 and SREBP2 drive the enhancer-promoter interaction to facilitate the recruitment of Mediator complex, thus upregulating MVA pathway genes. Together, our results establish that the epigenetic reader ZMYND8 endows YAP-high intestinal cancer with metabolic vulnerability.
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http://dx.doi.org/10.1016/j.molcel.2021.04.009DOI Listing
April 2021

Density functional theory study on the influence of tension and compression deformation on the electrical and phonon properties of monolayer and bilayer graphene.

J Mol Model 2021 Apr 26;27(5):138. Epub 2021 Apr 26.

College of physics, Shenyang Normal University, Liaoning, 110034, People's Republic of China.

Based on first-principles calculations using density functional theory, this paper systematically studies the effects of uniaxial tension-compression deformation on the stability and electrical and thermal properties of monolayer graphene and AA stacked bilayer graphene. The study shows that the original symmetry of graphene is broken by the tensile and compression deformations, catalyzing the interlayer coupling of bilayer graphene. Its electronic energy band, phonon dispersion, and other physical properties have changed. The transition from metalloid to semiconductor has completed since the deformation weakens the stability of the graphene system to varying degrees and opens the band gap of monolayer graphene. The band gap becomes larger with the increase of tensile and compressive deformation, in which way it can be adjusted. Influenced by the tiny tensile deformation, metalloid properties are exhibited by a small band gap of intrinsic AA-stacked bilayer graphene, and then the band gap becomes larger as the deformation increases. A band gap appears in the system phonon dispersion curves when the compression deformation increases to -15%. The phonon mode softens and shows virtual frequency. The value of virtual frequency increases with the increase of compression deformation. At the very moment, the vibration mode is discontinuous, and the system is unstable.
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http://dx.doi.org/10.1007/s00894-021-04748-7DOI Listing
April 2021

Artemisinin derivatives inhibit adipogenic differentiation of 3T3-L1 preadipocytes through upregulation of CHOP.

Biochem Biophys Res Commun 2021 Apr 21;557:309-315. Epub 2021 Apr 21.

Department of Central Laboratory, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China; Department of Plastic and Cosmetic Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. Electronic address:

Artemisinin derivatives could inhibit adipogenic differentiation of 3T3-L1 preadipocytes and prevent obesity in mice. However, the molecular mechanism remains largely unclear. Our research was designed to investigate the specific molecular target of artemisinin derivatives in adipogenic differentiation of 3T3-L1 preadipocytes. Here, we revealed that in response to dihydroartemisinin (DHA) or artesunate (ATS), intracellular lipid was decreased in a concentration dependent manner as shown by BODIPY staining. Quantitative PCR analysis showed that expression of Cebpa, Pparg, Fabp4 and Plin was significantly decreased by DHA treatment in a concentration and time dependent manner. Also, DHA treatment remarkably downregulated expression of CCAAT/enhancer-binding protein α (C/EBPα) and nuclear receptor peroxisome proliferation-activated receptor γ (PPARγ) of adipogenic induced 3T3-L1 cells as assayed by western blotting. RNA-seq analysis identified thousands of differential expression genes (DEGs), among which CHOP expression was significantly improved in DHA treated cells. Upregulation of CHOP was verified by quantitative PCR and western blotting, respectively. Knockdown of CHOP by the specific shRNA revealed that the inhibition of adipogenesis by DHA was strongly blocked, resulting in restored lipid accumulation and expression of adipogenic molecules. In conclusions, the inhibitory effect of DHA on adipogenic differentiation of 3T3-L1 preadipocytes was exerted in a concentration and time dependent manner, which was mediated by expression of CHOP.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.013DOI Listing
April 2021

Photoresponsive Micelles Enabling Codelivery of Nitric Oxide and Formaldehyde for Combinatorial Antibacterial Applications.

Biomacromolecules 2021 Apr 22. Epub 2021 Apr 22.

CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Science at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.

It is of particular interest to develop new antibacterial agents with low risk of drug resistance development and low toxicity toward mammalian cells to combat pathogen infections. Although gaseous signaling molecules (GSMs) such as nitric oxide (NO) and formaldehyde (FA) have broad-spectrum antibacterial performance and the low propensity of drug resistance development, many previous studies heavily focused on nanocarriers capable of delivering only one GSM. Herein, we developed a micellar nanoparticle platform that can simultaneously deliver NO and FA under visible light irradiation. An amphiphilic diblock copolymer of poly(ethylene oxide)--poly(4-((2-nitro-5-(((2-nitrobenzyl)oxy)methoxy)benzyl)(nitroso)amino)benzyl methacrylate) (PEO--PNNBM) was successfully synthesized through atom transfer radical polymerization (ATRP). The resulting diblock copolymer self-assembled into micellar nanoparticles without premature NO and FA leakage, whereas they underwent phototriggered disassembly with the corelease of NO and FA. We showed that the NO- and FA-releasing micellar nanoparticles exhibited a combinatorial antibacterial performance, efficiently killing both Gram-negative (e.g., ) and Gram-positive (e.g., ) bacteria with low toxicity to mammalian cells and low hemolytic property. This work provides new insights into the development of GSM-based antibacterial agents.
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http://dx.doi.org/10.1021/acs.biomac.1c00251DOI Listing
April 2021

Red Light-Triggered Intracellular Carbon Monoxide Release Enables Selective Eradication of MRSA Infection.

Angew Chem Int Ed Engl 2021 Apr 7. Epub 2021 Apr 7.

CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Science at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026, Anhui, China.

Carbon monoxide (CO) is an important gaseous signaling molecule. The use of CO-releasing molecules such as metal carbonyls enables the elucidation of the pleiotropic functions of CO. Although metal carbonyls show a broad-spectrum antimicrobial activity, it remains unclear whether the bactericidal property originates from the transition metals or the released CO. Here, we develop nonmetallic CO-releasing micelles via a photooxygenation mechanism of 3-hydroxyflavone derivatives, enabling CO release under red light irradiation (e.g., 650 nm). Unlike metal carbonyls that non-specifically internalize into both Gram-positive and Gram-negative bacteria, the nonmetallic micelles are selectively taken up by S. aureus instead of E. coli cells, exerting a selective bactericidal effect. Further, we demonstrate that the CO-releasing micelles can cure methicillin-resistant S. aureus (MRSA)-infected wounds, simultaneously eradicating MRSA pathogens and accelerating wound healing.
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http://dx.doi.org/10.1002/anie.202104024DOI Listing
April 2021

The complete chloroplast genome of Tibetan medicinal plant Maxim.

Mitochondrial DNA B Resour 2021 Mar 15;6(3):886-887. Epub 2021 Mar 15.

Qinghai Provincial Key Laboratory of Modernization of Traditional Chinese and Tibetan Medicine, Qinghai Provincial Drug Inspection and Testing Institute, Xining, China.

Maxim. is a traditional Tibetan medicine and widely used in the clinical pharmacology. In current study, the complete chloroplast genome of was reported. The total length of the genome was 155,144 bp with the GC content of 37.9%. We predicted 130 genes in the genome including 84 protein-coding genes, 37 tRNA genes, 8 rRNA genes and 1 pseudogene. 17 genes were duplicated in the IR regions including 7 tRNA, 4 rRNA and 6 protein-coding genes. Phylogenomic analysis revealed that forms a strong supported branch with and under the Rosaceae clade.
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http://dx.doi.org/10.1080/23802359.2021.1886013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971196PMC
March 2021

Dynamic content changes of cordycepin and adenosine and transcriptome in Cordyceps kyushuensis Kob at different fermentation stages.

Bioprocess Biosyst Eng 2021 Mar 30. Epub 2021 Mar 30.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, China.

20% (w/w) Astragali radix was added to the rice medium to cultivate C. kyushuensis Kob. The fermentation product was collected at mycelium stage, coloring stage, stromata-forming initial stage and fruiting body stage of C. kyushuensis Kob. The dynamic content changes of cordycepin and adenosine were detected at different fermentation stages. In the rice medium with Astragalus radix, both cordycepin and adenosine reached the highest content value on the 30th day of fermentation, 17.31 mg/g and 0.94 mg/g, respectively, which were 8.6 times and 2.0 times of that in rice medium at the same stage. At the same time, transcriptomics technology was used to analyze C. kyushuensis Kob during these four periods.
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http://dx.doi.org/10.1007/s00449-021-02561-3DOI Listing
March 2021

A novel de novo mutation in COL1A1 leading to osteogenesis imperfecta confirmed by zebrafish model.

Clin Chim Acta 2021 Jun 9;517:133-138. Epub 2021 Mar 9.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

Our study reports a novel dominant COL1A1 mutation in OI. Using a zebrafish model, we confirmed that the glycine to serine substitution at position 608 of the COL1A1 protein has deleterious effects on bone development.

Purpose: Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of genetic disorders. Mutations in two genes, collagen type I alpha 1 chain (COL1A1) and collagen type I alpha 1 chain (COL1A2), which encode the pro-a1 (I) and pro-a2 (I) chains of type I collagen, respectively, the most abundant form of collagen in the human body, cause most cases of OI.

Methods: In this study, we used panel-based next-generation sequencing for prenatal diagnosis of a fetus whose ultrasound images suggested OI. A de novo mutation in COL1A1 gene was suspected to cause the phenotype. To validate the effect of this mutation in a zebrafish model, we constructed a plasmid containing the corresponding mutation in the zebrafish gene col1a1a (c.1744 G > A), and overexpressed the mutant protein in zebrafish larvae.

Results: We identified a novel COL1A1 mutation (c.1822 G > A; p.Gly608Ser) in the fetus but not in her parents by an skeletal dysplasias panel. Bioinformatic analysis showed that the affected residue (p.Gly608) is highly conserved from zebrafish to humans. In contrast to larvae expressing wild-type (WT) col1a1a and enhanced green fluorescent protein (EGFP), col1a1a mutation-expressing larvae showed significant spinal curvature and embryonic lethality, mimicking the phenotype of human OI.

Conclusions: Our study revealed the pathogenicity of a de novo mutation, c.1822 G > A, in human COL1A1, which expands the mutation spectrum of OI.
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http://dx.doi.org/10.1016/j.cca.2021.02.024DOI Listing
June 2021

A Chinese multicenter retrospective study of isolated increased nuchal translucency associated chromosome anomaly and prenatal diagnostic suggestions.

Sci Rep 2021 Mar 10;11(1):5596. Epub 2021 Mar 10.

School of Computer Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Extensive researches involving fetuses with multiple ultrasound anomalies have been conducted over the years, but only few were focused on the isolated increased nuchal translucency (NT). On top of that, these limited number of researches were all designed as single-arm studies and the control group was missing. In this study, we conducted a multicenter, retrospective study using amniotic fluid samples collected from 1197 pregnant women having fetuses with isolated increased NT (INT group) or normal NT values (NNT group). Copy number variation sequencing (CNV-seq) was performed to determine their chromosome status and pathogenic variations were validated using SNP array. Overall, 59 chromosome aneuploidies, 34 pathogenic CNVs and 23 copy number variants of unknown significance (VOUS CNVs) were discovered. the INT group had a significantly higher proportion of aneuploidy (19.44%) and pathogenic CNV (8.33%) than the control group (3.49% and 2.30% respectively), and 88.89% of the pathogenic CNVs were related to heart defects. Additionally, more male fetuses were presented in the INT group (68.51%), but they did not have a higher risk (Relative Risk = 1.03) of carrying pathogenic chromosome variations than female fetuses. Our results demonstrated that fetuses with isolated increased NT had a distinct pattern of chromosome abnormality and majority of detected pathogenic CNVs could be linked to the congenital heart disease. Furthermore, because a considerable proportion of pathogenic CNVs were detected, we strongly recommend to perform a joint test of karyotyping and CNV analysis in prenatal diagnosis for fetuses with isolated increased NT in order to decrease the incident of missed diagnosis.
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http://dx.doi.org/10.1038/s41598-021-85108-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947009PMC
March 2021

The complete chloroplast genome of the Tibetan medicinal plant .

Mitochondrial DNA B Resour 2021 Jan 21;6(1):222-223. Epub 2021 Jan 21.

Qinghai Provincial Key Laboratory of Modernization of Traditional Chinese and Tibetan Medicine, Qinghai Provincial Drug Inspection and Testing Institute, Xining, China.

is a widely used Tibetan medicine. Here, we report the complete sequence of the chloroplast genome of The genome was 150,896 bp in length with 131 genes comprising 85 protein-coding genes, 37 tRNA genes, 8 rRNA genes and 1 pseudogene, with 20 of them occurring in double copies. Phylogenomic analysis suggested that forms a clade with , , and in genus.
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http://dx.doi.org/10.1080/23802359.2020.1861561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832499PMC
January 2021

Palladium-Catalyzed Allyl-Allyl Reductive Coupling of Allylamines or Allylic Alcohols with H as Sole Reductant.

Org Lett 2021 Jan 5;23(2):365-369. Epub 2021 Jan 5.

Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei 230026, P. R. China.

Catalytic carbon-carbon bond formation building on reductive coupling is a powerful method for the preparation of organic compounds. The identification of environmentally benign reductants is key for establishing an efficient reductive coupling reaction. Herein an efficient strategy enabling H as the sole reductant for the palladium-catalyzed allyl-allyl reductive coupling reaction is described. A wide range of allylamines and allylic alcohols as well as allylic ethers proceed smoothly to deliver the C-C coupling products under 1 atm of H. Kinetic studies suggested that the dinuclear palladium species was involved in the catalytic cycle.
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http://dx.doi.org/10.1021/acs.orglett.0c03865DOI Listing
January 2021

A modified rabbit model of tracheal stenosis and a household endoscope. More simplicity and accessibility.

Acta Cir Bras 2020 18;35(11):e351104. Epub 2020 Dec 18.

Master, Full Professor, Department of Pulmonary and Critical Care Medicine, Respiratory Medicine Center of Fujian Province, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China. Substantive scientific and intellectual contributions to the study, conception and design, manuscript preparation and writing, critical revision, final approval.

Purpose: To develop a simpler animal model for benign tracheal stenosis and introduce a low-cost household endoscope for postmodeling endotracheal evaluation.

Methods: Twenty rabbits were randomly divided into a model group (15 rabbits, subjected to transoral nylon brush scraping of the trachea) and a mock group (5 rabbits, merely exempted from scraping), a household endoscope was then introduced for weekly endoscopic examination. Meanwhile, other 15 rabbits (modeling like the model group) underwent batch tracheal resection at different postintervention times for pathological analysis.

Results: The model group presented a low mortality and few complications. The endoscope could obtain adequate images for stenosis assessment, which showed that the models presented homogeneous injury after scraping and developed a mature scar stricture at 28 days postoperatively with a mean stenosis degree of 65.9%, and 71.4% (10/14) above Myer-Cotton's grade II. The pathological findings were consistent with the clinicopathological process of human. No stenosis was found in mock group.

Conclusion: The modified model is simpler, minimally invasive and reliable, while the household endoscope is competent for model's follow-up, providing easily accessible and useful tools for facilitating more extensive studies of benign tracheal stenosis.
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http://dx.doi.org/10.1590/ACB351104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748079PMC
December 2020

Calcium Ion Chelation Preserves Platelet Function During Cold Storage.

Arterioscler Thromb Vasc Biol 2021 01 12;41(1):234-249. Epub 2020 Nov 12.

Gill Heart and Vascular Institute, Division of Cardiovascular Medicine, College of Medicine (B.X., G.Z., Y.Z., C.W., A.J.M., S.S.S., Z.L.), University of Kentucky, Lexington.

Objective: Platelet transfusion is a life-saving therapy to prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. However, for >6 decades, safe and effective strategies for platelet storage have been an impediment to widespread use of platelet transfusion. Refrigerated platelets are cleared rapidly from circulation, precluding cold storage of platelets for transfusion. Consequently, platelets are stored at room temperature with an upper limit of 5 days due to risks of bacterial contamination and loss of platelet function. This practice severely limits platelet availability for transfusion. This study is to identify the mechanism of platelet clearance after cold storage and develop a method for platelet cold storage. Approach and Results: We found that rapid clearance of cold-stored platelets was largely due to integrin activation and apoptosis. Deficiency of integrin β3 or caspase-3 prolonged cold-stored platelets in circulation. Pretreatment of platelets with EGTA, a cell impermeable calcium ion chelator, reversely inhibited cold storage-induced platelet activation and consequently prolonged circulation of cold-stored platelets. Moreover, transfusion of EGTA-treated, cold-stored platelets, but not room temperature-stored platelets, into the mice deficient in glycoprotein Ibα significantly shortened tail-bleeding times and diminished blood loss.

Conclusions: Integrin activation and apoptosis is the underlying mechanism of rapid clearance of platelets after cold storage. Addition of a cell impermeable calcium ion chelator to platelet products is potentially a simple and effective method to enable cold storage of platelets for transfusion.
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http://dx.doi.org/10.1161/ATVBAHA.120.314879DOI Listing
January 2021

Pediatric living donor left lateral segment liver transplantation for biliary atresia: Doppler ultrasound findings in early postoperative period.

Jpn J Radiol 2021 Apr 8;39(4):367-375. Epub 2020 Nov 8.

Department of Ultrasound, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin, 300192, China.

Purpose: To analyze hepatic hemodynamic parameters detected by Doppler ultrasound (DU) of uncomplicated children with biliary atresia who underwent left lateral segment living donor liver transplantation (LLS-LDLT), explore its normal change trend over time and determine the normal reference interval.

Methods: We retrospectively involved the data from 227 biliary atresia patients (100 Males,127 Females). Hemodynamic parameters include peak systolic velocity (PSV), end-diastolic velocity (EDV), resistivity index (RI), and pulsation index (PI) of the hepatic artery (HA), portal vein velocity (PVV), portal vein flow (PVF) and hepatic vein velocity (HVV) during intra-operative and on the 1st, 3rd, 5th and 7th day after operation were collected. Repeated measures analysis of the variance and Friedman test were used to analyze the changing trend of hemodynamic parameters over time in the first week after the operation.

Results: PSV and EDV showed a similar changing tendency at one week after surgery, with an overall decrease-rise trend; RI and PI also changed similarly with an overall rise-decrease trend. The HVV and PVV at surgery were lower than at all time points after surgery. As for PVF, the value of POD5 was the highest and then decreased. Additionally, this study provided the normal reference interval of hemodynamic parameters for LLS-LDLT patients, which were PSV: 18.4-98.3 cm/s, EDV: 0-43.3 cm/s, RI: 0.41-1.0, PI: 0.51-2.0, PVV: 19.0-83.7 cm/s, HVV: 19.4-68.0 cm/s, and PVF:99.5-500.0 ml/min/100 g at intraoperation. Within the first postoperative week: PSV: 21.0-97.7 cm/s, EDV: 0-32.7 cm/s, RI: 0.47-1.0, PI: 0.62-2.0, PVV: 23.0-92.0 cm/s, HVV: 19.7-86.0 cm/s, and PVF: 100.0-513.0 ml/min/100 g.

Conclusion: The hepatic hemodynamic of post-transplanted children detected by DU had specific changing trends and normal ranges, which provides valuable reference values for ultrasonologists and pediatric transplant clinicians.
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http://dx.doi.org/10.1007/s11604-020-01067-4DOI Listing
April 2021

A practical base mediated synthesis of 1,2,4-triazoles enabled by a deamination annulation strategy.

Chem Commun (Camb) 2020 Nov 28;56(91):14215-14218. Epub 2020 Oct 28.

Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education, Shan-dong Key Laboratory of Biochemical Analysis, Key Laboratory of Analytical Chem-istry for Life Science in Universities of Shandong, Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P. R. China.

A rapid and efficient base mediated synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed using the annulation of nitriles with hydrazines, which can be expanded to a wide range of triazoles in good to excellent yields. Ammonia gas is liberated during the reaction, and halo and hetero functional groups as well as free hydroxyl and amino groups are tolerated in this transformation. A variety of alkyl and aryl-substituted nitriles can be functionalized with aromatic and aliphatic hydrazines employing this procedure. This finding provides a practical and useful strategy for the synthesis of various N-labeled 1,2,4-triazole derivatives, and two types of mGlu5 receptor pharmaceuticals can be easily assembled in a one-pot manner.
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http://dx.doi.org/10.1039/d0cc05828aDOI Listing
November 2020

The Physiochemical Properties and Adsorption Characteristics of Processed Pomelo Peel as a Carrier for Epigallocatechin-3-Gallate.

Molecules 2020 Sep 16;25(18). Epub 2020 Sep 16.

College of Anxi Tea, Fujian Agriculture and Forestry University, Quanzhou 362406, China.

The NaOH-HCl- and ethanol-pretreated pomelo peel samples were prepared to apply to the batch adsorption for epigallocatechin-3-gallate (EGCG). The characteristics of peel samples were determined by Fourier transform infrared spectroscopy, scanning electron microscopy and a laser particle analyzer. The results of the physiochemical properties of the peel samples demonstrate that these peel samples have a promising adsorption capacity for EGCG, because of the increased potential binding sites on the surface compared with those of untreated peel samples. These two peel samples showed enhanced adsorption capacities of EGCG compared with that of unmodified peel in terms of the isothermal adsorption process, which could be described by both Langmuir and Freundlich models, with the theoretical maximum adsorption capacity of 77.52 and 94.34 mg g for the NaOH-HCl and ethanol-treated peel samples, respectively. The adsorption kinetics demonstrated an excellent fitness to pseudo-second-order, showing that chemisorption was the rate-limiting step. The thermodynamics analysis revealed that the adsorption reaction was a spontaneous and endothermic process. This work highlights that the processed pomelo peels have outstanding adsorption capacities for EGCG, which could be promising candidates for EGCG delivering in functional food application.
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http://dx.doi.org/10.3390/molecules25184249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571172PMC
September 2020

Immunomodulatory and Antioxidant Effects of Polysaccharides from the Parasitic Fungus .

Biomed Res Int 2020 29;2020:8257847. Epub 2020 Aug 29.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.

The ascomycete Cordyceps genus has been used as valued traditional Chinese medicine. is a unique species of Cordyceps, which parasitizes on the larvae of Walker, and its major component cordycepin and aqueous extract are known to have many pharmacological effects. However, the physiological function of water-soluble polysaccharides has not been explored in detail. In this study, to resolve these doubts, we extracted and separated Cordyceps-derived polysaccharides and then evaluated the immunomodulatory and antioxidant activities. Four polysaccharide fractions were purified from Cordyceps-cultured stroma by DEAE-cellulose 23 and Sephadex G-150 column chromatography. Basic structural information was elucidated on the basis of physicochemical property and spectroscopic evidences. The antioxidant activities were evaluated by a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical method and protective effect of DNA damage. The qualified immunologic activities were also determined and . The polysaccharides could stimulate the proliferation of mouse splenocytes whether concanavalin A (ConA) and lipopolysaccharide (LPS) existed or not, strengthen peritoneal macrophages to devour neutral red, and increase the content of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-) in serum. The research provides the corresponding evidence for Cordyceps polysaccharides as a potential candidate for functional foods and therapeutic agents.
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http://dx.doi.org/10.1155/2020/8257847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475740PMC
May 2021

Effectiveness of a Daily Rounding Checklist on Processes of Care and Outcomes in Diverse Pediatric Intensive Care Units Across the World.

J Trop Pediatr 2020 Aug 27. Epub 2020 Aug 27.

METRIC-Multidisciplinary and Translational Research in Intensive Care Medicine, Mayo Clinic, Rochester, MN, USA.

Background: Implementation of checklists has been shown to be effective in improving patient safety. This study aims to evaluate the effectiveness of implementation of a checklist for daily care processes into clinical practice of pediatric intensive care units (PICUs) with limited resources.

Methods: Prospective before-after study in eight PICUs from China, Congo, Croatia, Fiji, and India after implementation of a daily checklist into the ICU rounds.

Results: Seven hundred and thirty-five patients from eight centers were enrolled between 2015 and 2017. Baseline stage had 292 patients and post-implementation 443. The ICU length of stay post-implementation decreased significantly [9.4 (4-15.5) vs. 7.3 (3.4-13.4) days, p = 0.01], with a nominal improvement in the hospital length of stay [15.4 (8.4-25) vs. 12.6 (7.5-24.4) days, p = 0.055]. The hospital mortality and ICU mortality between baseline group and post-implementation group did not show a significant difference, 14.4% vs. 11.3%; p = 0.22 for each. There was a variable impact of checklist implementation on adherence to various processes of care recommendations. A decreased exposure in days was noticed for; mechanical ventilation from 42.6% to 33.8%, p < 0.01; central line from 31.3% to 25.3%, p < 0.01; and urinary catheter from 30.6% to 24.4%, p < 0.01. Although there was an increased utilization of antimicrobials (89.9-93.2%, p < 0.01).

Conclusions: Checklists for the treatment of acute illness and injury in the PICU setting marginally impacted the outcome and processes of care. The intervention led to increasing adherence with guidelines in multiple ICU processes and led to decreased length of stay.
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http://dx.doi.org/10.1093/tropej/fmaa058DOI Listing
August 2020

Photo-Degradable Micelles Capable of Releasing of Carbon Monoxide under Visible Light Irradiation.

Macromol Rapid Commun 2020 Sep 9;41(18):e2000323. Epub 2020 Aug 9.

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, 4072, Australia.

Carbon monoxide (CO) has emerged as a potential therapeutic agent for the treatment of many diseases. However, the therapeutic outcome is highly dependent on the dosages and administration sites. Hence, there is mounting interest in the development of CO-releasing materials to accomplish site-specific and dose-controlled delivery of CO. Herein, a micellar nanoparticle platform for the photo-mediated release of CO by using amphiphilic triblock copolymers bearing CO-releasing moieties of 3-hydroxylflavone (3-HF) derivatives within the middle blocks is developed. These micelles are relatively stable without CO leakage but undergo visible light-mediated CO release and simultaneous main chain scission. Moreover, these micellar nanoparticles are cytocompatible regardless of light irradiation, which shows unique anti-inflammatory performance only after light irradiation as a result of photo-triggered CO release. This work may represent the first example of main-chain degradable micellar nanocarriers with controlled CO-releasing performance for potential anti-inflammatory applications.
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http://dx.doi.org/10.1002/marc.202000323DOI Listing
September 2020

Base-mediated cascade amidination/N-alkylation of amines by alcohols.

Chem Commun (Camb) 2020 Sep 7;56(72):10489-10492. Epub 2020 Aug 7.

Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education, Shandong Key Laboratory of Biochemical Analysis, Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, College of Chemistry and Molecular Engineering. Qingdao University of Science and Technology, Qingdao 266042, P. R. China.

A base-mediated cascade amidination/N-alkylation reaction of amines by alcohols has been developed. For the first time, nitriles have been identified as an efficient and benign water acceptor reagent in N-alkylation. Notably, the procedure tolerates a series of functional groups, such as methoxyl, halo, vinyl and hetero groups, providing a convenient method to construct different substituted diamino compounds, N labeled amine and could be scaled up to 1 mol scale offering 138.7 g of the desired product in good yield in one-pot. Mechanistic studies provided strong evidence for the amidination of amines with nitriles facilitated by t-BuOK.
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http://dx.doi.org/10.1039/d0cc04831cDOI Listing
September 2020

Rapid access to 3-aminoindazoles from nitriles with hydrazines: a strategy to overcome the basicity barrier imparted by hydrazines.

Chem Commun (Camb) 2020 Aug;56(66):9521-9524

College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, P. R. China.

A practical and efficient base mediated synthesis of free 3-aminoindazoles has been developed from the reaction of nitriles with hydrazines, which successfully overcomes the difficulty of using aromatic hydrazines as substrates and allows for the synthesis of a wide range of N-aryl substituted free 3-aminoindazoles in moderate to excellent yields under mild conditions in one-pot. This finding provides a rapid and useful strategy for the synthesis of various functionalized 3-aminoindazole derivatives.
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http://dx.doi.org/10.1039/d0cc03789cDOI Listing
August 2020

Photo-degradable micelles for co-delivery of nitric oxide and doxorubicin.

J Mater Chem B 2020 08 13;8(31):7009-7017. Epub 2020 Jul 13.

CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Science at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, Anhui, China.

The emerging therapeutic potential of nitric oxide (NO) has spurred the rapid development of NO donors to maximize the therapeutic outcomes. Although polymeric NO donors have shown extended release times and optimized biodistributions, many of these macromolecular NO donors are non-degradable. Herein, we devise a macromolecular NO donor by integrating photoresponsive N,N'-dinitroso-p-phenylenediamine (DNP) derivatives into the middle block of an amphiphilic triblock copolymer and the photo-mediated NO release process transforms the DNP to quinondimine (QDI) moieties, enabling the degradation of the resulting polymers due to the spontaneous hydrolysis of QDI moieties. We demonstrated that the NO release process could be selectively activated under visible light irradiation both in vitro and in vivo. Moreover, the simultaneous release of NO and DOX could be achieved under visible light by taking advantage of the NO release-mediated micelle disassembly. This work provides new insights into the design of degradable macromolecular NO donors where the polymer breakdown could be actuated by triggered NO release.
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http://dx.doi.org/10.1039/d0tb00817fDOI Listing
August 2020

SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways.

Cancer Cell 2020 09 2;38(3):350-365.e7. Epub 2020 Jul 2.

CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China. Electronic address:

The level of SETD2-mediated H3K36me3 is inversely correlated with that of EZH2-catalyzed H3K27me3. Nevertheless, it remains unclear whether these two enzymatic activities are molecularly intertwined. Here, we report that SETD2 delays prostate cancer (PCa) metastasis via its substrate EZH2. We show that SETD2 methylates EZH2 which promotes EZH2 degradation. SETD2 deficiency induces a Polycomb-repressive chromatin state that enables cells to acquire metastatic traits. Conversely, mice harboring nonmethylated EZH2 mutant or SETD2 mutant defective in binding to EZH2 develop metastatic PCa. Furthermore, we identify that metformin-stimulated AMPK signaling converges at FOXO3 to stimulate SETD2 expression. Together, our results demonstrate that the SETD2-EZH2 axis integrates metabolic and epigenetic signaling to restrict PCa metastasis.
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http://dx.doi.org/10.1016/j.ccell.2020.05.022DOI Listing
September 2020

Can Viscoelasticity Measurements Obtained Through Shear-Wave US Elastography be used to Monitor Hepatic Ischemia-Reperfusion Injury and Treatment Response? An Animal Study.

Ultrasound Med Biol 2020 Sep 15;46(9):2464-2471. Epub 2020 Jun 15.

Department of Ultrasound, Tianjin First Center Hospital, Tianjin 300192, China.

This study aimed to investigate whether viscoelasticity measurements can be used to quantitatively analyze and monitor therapy response in hepatic ischemia-reperfusion injury (HIRI). All animals were divided into three groups: a sham operation group (n = 12), an ischemia-reperfusion injury (IRI) group (n = 12) and an andrographolide pre-treatment group (n = 6). To assess the feasibility of using shear-wave velocity (SWV) and shear-wave dispersion (SWD), shear-wave ultrasound elastography was applied onto IRI rats after 4 and 24 h of reperfusion or sham operation (each time point subgroup n = 6). For the verification experiments, six additional rats received andrographolide injection 2 h before IRI and were examined 24 h after reperfusion. The rats were sacrificed for biochemical and histopathological analyses after ultrasound scanning was performed. Compared with the sham group, the IRI group exhibited significantly higher SWD after both 4 and 24 h of reperfusion(10.69 ± 0.69 vs. 15.20 ± 3.23 and 9.01 ± 0.46 vs. 19.35 ± 0.86; p < 0.05). A positive correlation was found between SWD values and Suzuki's score (r = 0.621; p < 0.05). No correlation was found between SWV and Suzuki's score (r = 0.283; p > 0.05), although significant differences were found between the two groups after 24 h of reperfusion. Andrographolide treatment resulted in a significantly decreased SWD (15.24 ± 0.45 vs. 19.35 ± 0.86; p < 0.05), whereas SWV showed no statistically significant difference. This study demonstrated the potential of using viscoelasticity measurements for the diagnosis and therapeutic monitoring of HIRI, and that the use of SWD was significantly more advantageous than SWV.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.04.021DOI Listing
September 2020

Base-Mediated Amination of Alcohols Using Amidines.

J Org Chem 2020 Jun 3;85(12):7728-7738. Epub 2020 Jun 3.

Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing 210037, P. R. China.

Novel and efficient base-mediated -alkylation and amidation of amidines with alcohols have been developed, which can be carried out in one-pot reaction conditions, which allows for the synthesis of a wide range of -alkyl amines and free amides in good to excellent yields with high atom economy. In contrast to borrowing hydrogen/hydrogen autotransfer or oxidative-type -alkylation reactions, in which alcohols are activated by transition-metal-catalyzed or oxidative aerobic dehydrogenation, the use of amidines provides an effective surrogate of amines. This circumvents the inherent necessity in -alkylation of an oxidant or a catalyst to be stabilized by ligands.
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http://dx.doi.org/10.1021/acs.joc.0c00281DOI Listing
June 2020

Case report of holocarboxylase synthetase deficiency (late-onset) in 2 Chinese patients.

Medicine (Baltimore) 2020 May;99(18):e19964

Department of Pediatrics Intensive Care Unit, Chengdu Women's and Children's Central Hosptial, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.

Rationale: Holocarboxylase synthetase (HCLS) deficiency, especially the late-onset type, is a rare disease. Affected patients can present with irreversible metabolic acidosis and may be misdiagnosed with a glucose metabolic disorder. Prompt and correct diagnosis and treatment can reduce mortality to a great extent.

Patient Concerns: We report 2 Chinese patients who were diagnosed with late-onset HCLS deficiency. The age of onset of the 2 patients was approximately 8 months. The 2 patients had skin lesions, severe profound metabolic acidosis, dyspnea, and hyperglycemia.

Diagnoses: The results of urinary and blood organic acid analysis with gas chromatography/mass spectrometry revealed multiple carboxylase deficiency. Maple syrup urine disease and diabetic ketoacidosis could not be excluded. This finding is different from those of hypoglycemic complications reported in previous reports. Human genetic analysis eventually provided a definite diagnosis.

Interventions: Prompt oral treatment with biotin dramatically corrected the metabolic imbalances of the 2 patients, and continued oral biotin therapy was essential to the improvement of their prognoses.

Outcomes: Their metabolic disorders were corrected within 48 hours. During long-term follow-up, the patients achieved developmental milestones.

Lessons: Late-onset HCLS deficiency may present with obvious hyperglycemia. Human genetic analysis eventually provided a definite diagnosis. Prompt treatment with biotin is vital to correct metabolic imbalances, and continued therapy is essential to the improving long-term prognoses. Their mutations were p.R508W and c.1088T > A, and these mutations might represent hot-spot genes in Chinese populations with HCLS deficiency. The variants c.1484T > G(p.L495*) and c.835G > T(p.E279x) are likely pathogenic, and more studies are needed to confirm these results.
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http://dx.doi.org/10.1097/MD.0000000000019964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440356PMC
May 2020

Regulating vesicle bilayer permeability and selectivity via stimuli-triggered polymersome-to-PICsome transition.

Nat Commun 2020 03 23;11(1):1524. Epub 2020 Mar 23.

CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, 230026, Hefei, Anhui, China.

Compared to liposomes, polymersomes of block copolymers (BCPs) possess enhanced stability, along with compromised bilayer permeability. Though polyion complex vesicles (PICsomes) from oppositely charged block polyelectrolytes possess semipermeable bilayers, they are unstable towards physiologically relevant ionic strength and temperature; moreover, permselectivity tuning of PICsomes has remained a challenge. Starting from a single component diblock or triblock precursor, we solve this dilemma by stimuli-triggered chemical reactions within pre-organized BCP vesicles, actuating in situ polymersome-to-PICsome transition and achieving molecular size-selective cargo release at tunable rates. UV light and reductive milieu were utilized to trigger carboxyl decaging and generate ion pairs within hydrophobic polymersome bilayers containing tertiary amines. Contrary to conventional PICsomes, in situ generated ones are highly stable towards extreme pH range (pH 2-12), ionic strength (~3 M NaCl), and elevated temperature (70 °C) due to multivalent ion-pair interactions at high local concentration and cooperative hydrogen bonding interactions of pre-organized carbamate linkages.
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http://dx.doi.org/10.1038/s41467-020-15304-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090076PMC
March 2020

Fatsia Japonica-Derived Hierarchical Porous Carbon for Supercapacitors With High Energy Density and Long Cycle Life.

Front Chem 2020 20;8:89. Epub 2020 Feb 20.

Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Materials Science and Engineering, Nanjing Forestry University, Nanjing, China.

Fatsia Japonica seed, which is mainly composed of glucose, has potential as a porous carbon matrix precursor for supercapacitors that can achieve high-value utilization. Cost-effective hierarchical porous carbon materials (HPC) were prepared from Fatsia Japonica by annealing at high temperature. The pore size and distribution of the HPC can be precisely controlled and adjusted by altering the activation temperature. The HPC obtained at 600°C showed favorable features for electrochemical energy storage, with a surface area of 870.3 m/g. The HPC for supercapacitors (a three-electrode system) exhibited good specific capacitance of 140 F/g at a current density of 1 A/g and a long cycling life stability (87.5% remained after 10,000 cycles). In addition, the HPC electrode showed an excellent energy density of 23 Wh/Kg. Such hierarchical porous biomass-derived carbon would be a good candidate for application in the electrodes of supercapacitors due to its simple preparation process and the outstanding electrochemical performance.
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http://dx.doi.org/10.3389/fchem.2020.00089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044675PMC
February 2020

Dose Effect of Bovine Lactoferrin Fortification on Iron Metabolism of Anemic Infants.

J Nutr Sci Vitaminol (Tokyo) 2020 ;66(1):24-31

School of Exercise and Nutritional Sciences, San Diego State University.

To evaluate the effect of iron-fortified formula with different concentrations of bovine lactoferrin (bLF) on improvement of anemic status in term infants who were previously breast-fed. A randomized, controlled, open, and post-market intervention study. A total of 108 infants aged 6-9 mo who were previously breast-fed and weaned were selected. The subjects were divided into three groups with the sequence of outpatient: fortified group 1 (FG1) with a bLF concentration of 38 mg/100 g, FG2 with 76 mg/100 g bLF, FG0 with no bLF. The intervention duration was 3 mo. Weight, height, head circumference and the concentration of hemoglobin (Hb), serum ferritin (SF), serum transferring receptor (sTfR) were measured and sTfR-SF index (TFR-F index) and total body iron content (TBIC) were computed before and after intervention. The primary outcome measures were obtained from 96 infants (35, 33 and 28 for FG0, FG1 and FG2, respectively). After 1 mo of intervention, the changes of Hb level showed no significant difference (p>0.05) among the three groups, however, the Hb level of infants in FG2 were significantly higher than those of infants in the other two groups after 3 mo of intervention (p<0.05). The present data indicated that the formula fortified with 76 mg/100 g bLF positively affected the Hb of anemic infants who were previously breastfed when compared with fortification with 38 mg/100 g bLF and no bLF fortification.
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http://dx.doi.org/10.3177/jnsv.66.24DOI Listing
December 2020

Light-triggered nitric oxide (NO) release from photoresponsive polymersomes for corneal wound healing.

Chem Sci 2020 Jan 5;11(1):186-194. Epub 2019 Nov 5.

CAS Key Laboratory of Soft Matter Chemistry , Hefei National Laboratory for Physical Science at the Microscale , Department of Polymer Science and Engineering , University of Science and Technology of China , Hefei 230026 , Anhui , China . Email:

Polymersomes have been extensively used in the delivery of both small and macromolecular payloads. However, the controlled delivery of gaseous therapeutics (, nitric oxide, NO) remains a grand challenge due to its difficulty in loading of gaseous payloads into polymersomes without premature leakage. Herein, NO-releasing vesicles could be fabricated the self-assembly of NO-releasing amphiphiles, which were synthesized by the direct polymerization of photoresponsive NO monomers (abbreviated as NBN, NBN, and BN). These monomers were rationally designed through the integration of the photoresponsive behavior of -nitrosoamine moieties and the self-immolative chemistry of 4-aminobenzyl alcohol derivatives, which outperformed conventional NO donors such as diazeniumdiolates (NONOates) and -nitrosothiols (SNOs) in terms of ease of preparation, stability of storage, and controllability of NO release. The unique design made it possible to selectively release NO by a light stimulus and to regulate the NO release rates. Importantly, the photo-mediated NO release could be manipulated in living cells and showed promising applications in the treatment of corneal wounds. In addition to delivering NO, the current design enabled the synergistic delivery of NO and other therapeutic payloads by taking advantage of NO release-mediated traceless crosslinking of the vesicles.
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http://dx.doi.org/10.1039/c9sc04039kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012058PMC
January 2020