Publications by authors named "Di Fan"

117 Publications

Extraction of Noncondensed Lignin from Poplar Sawdusts with -Toluenesulfonic Acid and Ethanol.

J Agric Food Chem 2021 Sep 13. Epub 2021 Sep 13.

School of Chemistry & Chemical Engineering, South China University of Technology, Guangzhou 510640, P. R. China.

The traditional pretreatment leads to the recalcitration of C-C bonds during lignin fractionation, thus hindering their depolymerization into aromatic monomers. It is essential to develop an applicable approach to extract noncondensed lignin for its high-value applications. In this work, noncondensed lignins were extracted from poplar sawdust using recyclable -toluenesulfonic acid for cleaving lignin-carbohydrate complex bonds effectively and ethanol as a stabilization reagent to inhibit lignin condensation. Lignin yield of 83.74% was recovered by 3 mol/L acid in ethanol at 85 °C for 5 h, and carbohydrates were well preserved (retaining 98.97% cellulose and 50.01% hemicelluloses). During lignin fractionation, the acid concentration and extraction time were the major drivers of condensation. Ethanol reacted with lignin at the α-position to prevent the formation of the condensed structure. The extracted lignin depolymerized over the Pd/C catalysts gave a yield of 50.35% of aromatic monomers, suggesting that the novel extraction process provided a promising way for noncondensed lignin production.
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http://dx.doi.org/10.1021/acs.jafc.1c03774DOI Listing
September 2021

Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies.

Am J Physiol Cell Physiol 2021 09 8. Epub 2021 Sep 8.

Lab of Theoretical and Computational Nanoscience, CAS Key Lab of Nanophotonic Materials and Devices, CAS Key Lab of Standardization & Measurement for Nanotechnology, CAS Ctr for Excellence in Nanoscience, Beijing Key Lab of Ambient Particles Health Effects & Prevention Techniques, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, China.

Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their non-invasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.
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http://dx.doi.org/10.1152/ajpcell.00048.2021DOI Listing
September 2021

High-dose intravenous vitamin C attenuates hyperinflammation in severe coronavirus disease 2019.

Nutrition 2021 Jun 26;91-92:111405. Epub 2021 Jun 26.

Department of Cardiology, Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Province, China.

Objective: High-dose intravenous vitamin C (HIVC) is a major concern when treating patients with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the clinical efficacy of HIVC on hyperinflammation in patients with severe COVID-19.

Methods: This retrospective cohort study included hospitalized patients with severe COVID-19, a subset of whom was treated with HIVC. The medical records were screened for demographic data, laboratory findings, and medications, as well as initial and repeated values of multiple inflammatory markers for analysis.

Results: A high percentage of patients presented with hyperinflammation based on inflammatory marker levels above the upper limit of normal (high-sensitivity C-reactive protein, 80.1%; interleukin-6, 91.5%; and tumor necrosis factor-α, 67.4%). Eighty-five (36%) patients received HIVC therapy. After treatment with HIVC, the levels of inflammatory markers displayed a significant decrease compared with those of patients without HIVC. Furthermore, the percentages of reduction in inflammatory marker levels were higher in patients receiving HIVC compared with those in patients treated without HIVC. Stepwise multiple linear regression analysis revealed that HIVC was independently associated with percentages of reduction in levels of inflammatory markers.

Conclusions: HIVC has the potential benefit of attenuating hyperinflammation by reducing inflammatory marker levels in patients with severe COVID-19.
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http://dx.doi.org/10.1016/j.nut.2021.111405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234258PMC
June 2021

Adsorption-Enhanced Glucan Oligomer Production from Cellulose Hydrolysis over Hyper-Cross-Linked Polymer in Molten Salt Hydrate.

ACS Appl Mater Interfaces 2021 Aug 12. Epub 2021 Aug 12.

Department of Chemical Engineering, University of Massachusetts-Amherst, 159 Goessman Lab, 686 N Pleasant Street, Amherst, Massachusetts01003, United States.

Selective saccharification of cellulose into glucose is a critical step for utilization of lignocellulosic biomass. Molten salt hydrates (MSHs) have shown promising performance in selectively converting cellulose into glucose because of the high solubility of cellulose in the solvent. However, the separation of formed glucose from the MSHs is still a grand challenge. To address this issue, we developed a two-step process, where crystalline cellulose is hydrolyzed into short-chain glucan oligomers in MSHs followed by separation and subsequent hydrolysis of the formed oligomers into glucose under mild conditions. The two-step method provides an easy separation for glucan oligomers from the MSHs without sacrificing the selectivity to glucose. Application of the method for crystalline cellulose is, however, limited to a relatively low concentration, 26.2 mg/mL, because of the formation of byproducts in the MSH that facilitate oligomers degradation. In this work, reactive adsorption was employed to in situ remove the byproducts formed during cellulose hydrolysis in the MSH. It was found that hyper-cross-linked polymer (HCP) made from the polymerization of 4-vinylbenzyl chloride and divinylbenzene can selectively adsorb 5-hydroxymethylfurfural (5-HMF) and levulinic acid (LA) while showing negligible sugar adsorption in both water and the MSH. With the reactive adsorption approach, byproducts including 5-HMF and LA were removed from the reaction media under reaction conditions, and their negative effects on oligomer degradation were inhibited. In the presence of the HCP, the obtained glucan oligomer concentration was enhanced from less than 54.2 to 247.1 mg mL when the weight ratio of cellulose was increased to MSH from 1:60 to 1:4, exhibiting an oligomer yield of 69.5%. The HCP can be effectively separated from the reaction media by filtration and regenerated by oxidation with hydrogen peroxide. Application of reactive adsorption with HCP for cellulose hydrolysis in the MSH provides a promising method to produce glucan oligomers and glucose with an improved yield and efficiency.
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http://dx.doi.org/10.1021/acsami.1c09360DOI Listing
August 2021

Long non-coding RNA Pvt1 modulates the pathological cardiac hypertrophy via miR-196b-mediated OSMR regulation.

Cell Signal 2021 Oct 8;86:110077. Epub 2021 Jul 8.

Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China; The Fifth Affiliated Hospital of Xin Jiang medical University, Department of Cardiology, Urumchi 830001, China. Electronic address:

Cardiac hypertrophy is the uppermost risk factor for the development of heart failure, leading to irreversible cardiac structural remodeling and sudden death. As a major mediator of cardiac remodeling, oncostatin M (OSM) and its receptor, OSMR, attract plenty of interest. Recent studies have demonstrated key effects of noncoding RNAs on myocardial remodeling. However, whether noncoding RNAs that regulate the expression of OSMR would regulate the process of remodeling remain unclear. Herein, we observed that long noncoding RNA (lncRNA) Pvt1 expression showed to be significantly elicited by aortic banding (AB) operation in vivo and by angiotensin (Ang II) treatment in vitro. Pvt1 knockdown significantly attenuated the myocardial hypertrophy caused by pressure overload within rats and the cardiac myocyte hypertrophy caused by Ang II in vitro. Moreover, Pvt1 knockdown also decreased cellular myomesin and B-raf, which was involved in OSM function in cardiac remodeling. Based on online tools prediction, miR-196b may simultaneously target Pvt1 and OSMR 3' untranslated region (UTR). In rat H9c2 cells and primary cardiac myocyte, Pvt1 and miR-196b exerted negative regulatory effects on each other and miR-196b negatively regulated OSMR expression. Pvt1 directly targeted miR-196b to relieve miR-196b-induced OSMR suppression via acting as a competing endogenous RNA (ceRNA). Moreover, the effect of miR-196b suppression upon the B-raf was opposite to Pvt1 knockdown, and miR-196b suppression might significantly attenuate the effect of Pvt1 knockdown. In summary, Pvt1/miR-196b axis modulating cardiomyocyte hypertrophy and remodeling via OSMR. Our findings provide a rationale for further studies on the potential therapeutic benefits of Pvt1 function and mechanism in cardiac and cardiomyocyte hypertrophy by a lncRNA-miRNA-mRNA network.
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http://dx.doi.org/10.1016/j.cellsig.2021.110077DOI Listing
October 2021

Characterization of Selected Plant Growth-Promoting Rhizobacteria and Their Non-Host Growth Promotion Effects.

Microbiol Spectr 2021 Sep 30;9(1):e0027921. Epub 2021 Jun 30.

Department of Plant Science, McGill University, Macdonald Campus, Sainte-Anne-de-Bellevue, Quebec, Canada.

Plant growth-promoting rhizobacteria (PGPR) are a functionally diverse group of microbes having immense potential as biostimulants and biopesticides. We isolated four PGPR (designated n, L, K, and Y) that confer growth-promoting effects on Arabidopsis thaliana. The present study describes the detailed polyphasic characterization of these PGPR. Classical methods of bacterial identification and biochemical test kits (API20E, API20NE, API ZYM, and API 50CH) revealed their metabolic versatility. All rhizobacterial isolates were positive for 1-aminocyclopropane-1-carboxylate (ACC) deaminase (ACCD) and indole acetic acid production and phosphorous solubilization. PCR analysis confirmed the presence of the gene in strains n, L, and Y, showing their N-fixation potential. dual culture methods and bacterial infestation demonstrated that strains n and L exerted antagonistic effects on Pseudomonas syringae pv. tomato DC3000 and 191 and provided protection to plants against both phytopathogens. Short- or long-term bacterial treatment revealed significant changes in transcript levels of genes annotated to stress response and hormone metabolism in . In particular, the expression of stress-responsive genes in showed an upregulation under salinity stress. MAP kinase 6 (MPK6) was involved in the growth promotion induced by the four bacterial strains. Furthermore, these strains caused a significant increase in root dry weight of maize seedlings under gnotobiotic conditions. We conclude that the four rhizobacteria are good candidates as biofertilizers for enhancing growth of maize, among which strains n and L showed marked plant growth-promoting attributes and the potential to be exploited as functional biostimulants and biopesticides for sustainable agriculture. There are pressing needs to reduce the use of agrochemicals, and PGPR are receiving increasing interest in plant growth promotion and disease protection. This study follows up our previous report that the four newly isolated rhizobacteria promote the growth of Arabidopsis thaliana. We test the hypothesis that they have multiple PGP traits and that they can be used as biofertilizers and biopesticides. assays indicated that these four strains have various PGP properties related to nutrient availability, stress resistance, and/or pest organism antagonism. They significantly influenced the transcript levels of genes involved in stress response and hormone metabolism in . MPK6 is indispensable to the growth stimulation effects. Strains n and L protected seedlings against phytopathogens. Three strains significantly increased maize growth . In summary, introducing these four strains onto plant roots provides a benefit to the plants. This is the first study regarding the potential mechanism(s) applied by sp. as biostimulants.
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http://dx.doi.org/10.1128/Spectrum.00279-21DOI Listing
September 2021

Assessing right ventricular systolic function using ultrasonic speckle-tracking imaging in repaired Tetralogy of Fallot with different pulmonary artery branch angles.

Echocardiography 2021 01 3;38(1):89-96. Epub 2020 Dec 3.

Department of Echocardiography Diagnosis, Children's Hospital of Hebei Province, Hebei Medical University, Shijiazhuang, China.

Objective: This study assessed whether ultrasonic speckle-tracking imaging (STI) could help evaluate right ventricular systolic function in repaired Tetralogy of Fallot (TOF) with different pulmonary artery branch angles.

Methods: We retrospectively evaluated 64 patients who underwent surgery for TOF and 60 normal children. The angle between the left pulmonary artery and main pulmonary artery was measured using echocardiography and computed tomography angiography (CTA). Furthermore, STI was used to record the global longitudinal strain of the four-chamber view (GLS4), the global longitudinal strain of the two-chamber view (GLS2), and the global longitudinal strain of the right ventricle (RVGLS).

Results: The GLS4, GLS2, and RVGLS values in the TOF groups with different pulmonary artery branch angles were significantly lower than those in the control group. Furthermore, the GLS2 and RVGLS values were significantly lower for angles of 90-100° and <90° (vs >100°). Multivariate linear regression analyses revealed that pulmonary regurgitation and the angle between the left and main pulmonary arteries were two important factors affecting RVGLS. The Bland-Altman consistency test revealed good agreement regarding the pulmonary artery branch angles measured using echocardiography and CTA.

Conclusion: In patients with TOF, the RVGLS was lower for acute left pulmonary artery angulation than for round and blunt left pulmonary artery angulation. The angle of the pulmonary artery branches was an important factor affecting RVGLS. Echocardiography can be used to measure the angle of the pulmonary artery branches, which provides valuable information for surgical correction of pulmonary artery morphology.
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http://dx.doi.org/10.1111/echo.14948DOI Listing
January 2021

Plasmid DNA-Based Bioluminescence-Activated System for Photodynamic Therapy in Cancer Treatment.

ChemMedChem 2021 Jun 4;16(12):1967-1974. Epub 2021 Mar 4.

College of Chemistry and Materials Science, Jiangsu Key Laboratory of Bio-functional Materials, Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials, Key Laboratory of Applied Photochemistry, Nanjing Normal University, Nanjing, 210023, P. R. China.

The low depth of tissue penetration by therapeutic light sources severely restricts photodynamic therapy (PDT) in treating deep-seated tumors. Using a luciferase/d-luciferin bioluminescence system to artificially create internal light sources in cells instead of external light sources is an effective means of solving the above problems. However, high-efficiency bioluminescence requires a higher concentration of luciferase in the cell, which poses a considerable challenge to the existing system of enzyme loading, delivery, activity and retention of drugs, and dramatically increases the cost of treatment. We loaded the substrate D-luciferin, and the photosensitizer hypericin into a polyethyleneimine (PEI)-modified nano-calcium phosphate (CaP) to solve this problem. Subsequently, the plasmid DNA containing the luciferase gene was loaded onto it using the high-density positive charge characteristic of PEI from the nanodrug (denoted DHDC). After the DHDC enters the tumor cell, it collapses and releases the plasmid DNA, which uses the intracellular protein synthesis system to continuously and massively express luciferase. Using endogenous ATP, Mg , and O in cells, luciferase oxidizes d-luciferin and produces luminescence. The luminescence triggers hypericin excitation to generate ROS and kill cancer cells. This study provides a new strategy for the application of bioluminescence in PDT treatment.
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http://dx.doi.org/10.1002/cmdc.202000979DOI Listing
June 2021

Hyper-Inflammatory Response Involves in Cardiac Injury Among Patients With Coronavirus Disease 2019.

Am J Med Sci 2021 06 12;361(6):718-724. Epub 2021 Feb 12.

Department of Cardiology, Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 West 5th Road, Xi'an 710004, Shaanxi, China.

Background: Inflammation can facilitate development of coronavirus disease 2019 (COVID-19) and cardiac injury is associated with worse clinical outcomes. However, data are relatively scarce on the association between hyper-inflammatory response and cardiac injury among COVID-19 patients.

Methods: The study was designed based on severe and critically ill patients with COVID-19. Information on clinical characteristics and laboratory examinations was collected from the electronic medical records and analyzed.

Results: There were 32.4% (n = 107) of patients with cardiac injury. The median age was 67 years, and 48.8% (n = 161) of patients were men. Hypertension was the most common in 161 (48.8%) patients, followed by diabetes (16.7%, n = 55) and coronary heart disease (13.3%, n = 44). Compared to cases without cardiac injury, those with cardiac injury were older, had higher proportions of coronary heart disease, and leukocyte counts, significantly elevated concentrations of N-terminal pro-B-Type natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6, and IL-8, but lower lymphocyte counts. A significant positive correlation was observed between high-sensitivity troponin I and inflammatory cytokines. Logistic regression analysis showed that hs-CRP, TNF-α and IL-6 were independent risk factors for cardiac injury.

Conclusions: Cardiac injury was associated with elevated levels of inflammatory cytokines among severe and critically ill patients with COVID-19, suggesting that hyper-inflammatory response may involve in cardiac injury.
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http://dx.doi.org/10.1016/j.amjms.2021.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879031PMC
June 2021

Siderophores for medical applications: Imaging, sensors, and therapeutics.

Authors:
Di Fan Qiaojun Fang

Int J Pharm 2021 Mar 1;597:120306. Epub 2021 Feb 1.

Laboratory of Theoretical and Computational Nanoscience, CAS Key Laboratory of Nanophotonic Materials and Devices, CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Ambient Particles Health Effects and Prevention Techniques, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, PR China; Sino-Danish Center for Education and Research, Beijing 101408, PR China. Electronic address:

Siderophores are low-molecular-weight chelators produced by microorganisms to scavenge iron from the environment and deliver it to cells via specific receptors. Tremendous researches on the molecular basis of siderophore regulation, synthesis, secretion, and uptake have inspired their diverse applications in the medical field. Replacing iron with radionuclides in siderophores, such as the most prominent Ga-68 for positron emission tomography (PET), carves out ways for targeted imaging of infectious diseases and cancers. Additionally, the high affinity of siderophores for metal ions or microorganisms makes them a potent detecting moiety in sensors that can be used for diagnosis. As for therapeutics, the notable Trojan horse-inspired siderophore-antibiotic conjugates demonstrate enhanced toxicity against multi-drug resistant (MDR) pathogens. Besides, siderophores can tackle iron overload diseases and, when combined with moieties such as hydrogels and nanoparticles, a wide spectrum of iron-induced diseases and even cancers. In this review, we briefly outline the related mechanisms, before summarizing the siderophore-based applications in imaging, sensors, and therapeutics.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120306DOI Listing
March 2021

The microRNA476a-RFL module regulates adventitious root formation through a mitochondria-dependent pathway in Populus.

New Phytol 2021 06 24;230(5):2011-2028. Epub 2021 Mar 24.

Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation, School of Life Sciences, Southwest University, Chongqing, 400715, China.

For woody plants, clonal propagation efficiency is largely determined by adventitious root (AR) formation at the bases of stem cuttings. However, our understanding of the molecular mechanisms contributing to AR morphogenesis in trees remains limited, despite the importance of vegetative propagation, currently the most common practice for tree breeding and commercialization. Here, we identified Populus-specific miR476a as a regulator of wound-induced adventitious rooting that acts by orchestrating mitochondrial homeostasis. MiR476a exhibited inducible expression during AR formation and directly targeted several Restorer of Fertility like (RFL) genes encoding mitochondrion-localized pentatricopeptide repeat proteins. Genetic modification of miR476a-RFL expression revealed that miR476a/RFL-mediated dynamic regulation of mitochondrial homeostasis influences AR formation in poplar. Mitochondrial perturbation via exogenous application of a chemical inhibitor indicated that miR476a/RFL-directed AR formation depends on mitochondrial regulation that acts via auxin signaling. Our results thus establish a microRNA-directed mitochondrion-auxin signaling cascade required for AR development, providing insights into the role of mitochondrial regulation in the developmental plasticity of plants.
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http://dx.doi.org/10.1111/nph.17252DOI Listing
June 2021

6-Gingerol protects against cardiac remodeling by inhibiting the p38 mitogen-activated protein kinase pathway.

Acta Pharmacol Sin 2021 Jan 18. Epub 2021 Jan 18.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

6-Gingerol, a pungent ingredient of ginger, has been reported to possess anti-inflammatory and antioxidant activities, but the effect of 6-gingerol on pressure overload-induced cardiac remodeling remains inconclusive. In this study, we investigated the effect of 6-gingerol on cardiac remodeling in in vivo and in vitro models, and to clarify the underlying mechanisms. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 6-gingerol (20 mg/kg, ig) three times a week (1 week in advance and continued until the end of the experiment). Four weeks after TAC surgery, the mice were subjected to echocardiography, and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes and cardiac fibroblasts were used to validate the protective effects of 6-gingerol in response to phenylephrine (PE) and transforming growth factor-β (TGF-β) challenge. We showed that 6-gingerol administration protected against pressure overload-induced cardiac hypertrophy, fibrosis, inflammation, and dysfunction in TAC mice. In the in vitro study, we showed that treatment with 6-gingerol (20 μM) blocked PE-induced-cardiomyocyte hypertrophy and TGF-β-induced cardiac fibroblast activation. Furthermore, 6-gingerol treatment significantly decreased mitogen-activated protein kinase p38 (p38) phosphorylation in response to pressure overload in vivo and extracellular stimuli in vitro, which was upregulated in the absence of 6-gingerol treatment. Moreover, transfection with mitogen-activated protein kinase kinase 6 expressing adenoviruses (Ad-MKK6), which specifically activated p38, abolished the protective effects of 6-gingerol in both in vitro and in vivo models. In conclusion, 6-gingerol improves cardiac function and alleviates cardiac remodeling induced by pressure overload in a p38-dependent manner. The present study demonstrates that 6-gingerol is a promising agent for the intervention of pathological cardiac remodeling.
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http://dx.doi.org/10.1038/s41401-020-00587-zDOI Listing
January 2021

BMI1 in the heart: Novel functions beyond tumorigenesis.

EBioMedicine 2021 Jan 6;63:103193. Epub 2021 Jan 6.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, PR China. Electronic address:

The BMI1 protein, a member of the PRC1 family, is a well recognised transcriptional suppressor and has the capability of maintaining the self-renewal and proliferation of tissue-specific stem cells. Numerous studies have established that BMI1 is highly expressed in a variety of malignant cancers and serves as a key regulator in the tumorigenesis process. However, our understanding of BMI1 in terminally differentiated organs, such as the heart, is relatively nascent. Importantly, emerging data support that, beyond the tumor, BMI1 is also expressed in the heart tissue and indeed exerts profound effects in various cardiac pathological conditions. This review gives a summary of the novel functions of BMI1 in the heart, including BMI1-positive cardiac stem cells and BMI1-mediated signaling pathways, which are involved in the response to various cardiac pathological stimuli. Besides, we summarize the recent progress of BMI1 in some novel and rapidly developing cardiovascular therapies. Furtherly, we highlight the properties of BMI1, a therapeutic target proved effective in cancer treatment, as a promising target to alleviate cardiovascular diseases.
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http://dx.doi.org/10.1016/j.ebiom.2020.103193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804972PMC
January 2021

TMEM173 protects against pressure overload-induced cardiac hypertrophy by modulating autophagy.

J Cell Physiol 2021 Jul 23;236(7):5176-5192. Epub 2020 Dec 23.

Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, China.

TMEM173 has been reported to participate in endoplasmic reticulum stress, inflammation and immunology, all of which closely involved with cardiac hypertrophy. But its role in autophagy is not fully figured out. In our research, Tmem173 global knockout (KO) mice manifested more deteriorated hypertrophy, fibrosis, inflammatory infiltration and cardiac malfunction compared with wild type C57BL/6 mice after 6 weeks of transverse aortic constriction. And KO mice showed inhibited autophagosome degradation in myocardium observed under transmission electron microscope and in protein level. In in vitro experiments conducted in neonatal rat cardiomyocytes under phenylephrine treatment, the abundance of Tmem173 gene was negatively related to the abundance of LC3-Ⅱ and the number of red and yellow fluorescent dots, of which reflected the capacity of autophagosome degradation. These results indicated that TMEM173 might be a promoter of autophagic flux and protected against pressure overload-induced cardiac hypertrophy. It may serve as a potential therapeutic target for cardiac hypertrophy in the future.
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http://dx.doi.org/10.1002/jcp.30223DOI Listing
July 2021

Hyaluronic acid thiol modified injectable hydrogel: Synthesis, characterization, drug release, cellular drug uptake and anticancer activity.

Carbohydr Polym 2021 Feb 22;254:117286. Epub 2020 Oct 22.

College of Chemistry and Materials Science, Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials, Key Laboratory of Applied Photochemistry, Nanjing Normal University, Nanjing, 210023, China; School of Chemistry and Chemical Engineering, Yancheng Institute of Technology, Yancheng, Jiangsu, 224051, China. Electronic address:

Dimethyl sulfoxide (DMSO) is an excellent solvent for various types of anticancer drugs. Here, beyond that, it can participate in a disulfide bond crosslink between sulfhydryl (-SH) modified hyaluronic acid (HA-SH) molecules to form the hydrogel. Thus, during the above crosslink process, the dissolved drug in DMSO could be effectively loaded inside the hydrogels' porous structures as an injectable peritumoral implant. The loaded drugs can be sustained released through hydrogel swelling and degradation around the tumor tissue to suppress tumor growth. In this paper, the above hydrogel was used as a peritumoral drug-loaded implant for chemotherapeutics, photosensitizer, and photothermal reagent, respectively, for chemotherapy, photodynamic therapy, and photothermal therapy in cancer treatment. Therefore, this DMSO involved HA-SS-HA (HA, hyaluronic acid; -SS-, disulfide bond) hydrogel fabrication method is simple and widely applicable for drug-loaded peritumoral implant preparation.
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http://dx.doi.org/10.1016/j.carbpol.2020.117286DOI Listing
February 2021

Histone methyltransferase ATX1 dynamically regulates fiber secondary cell wall biosynthesis in Arabidopsis inflorescence stem.

Nucleic Acids Res 2021 01;49(1):190-205

Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation, School of Life Sciences, Southwest University, Chongqing 400715, China.

Secondary wall thickening in the sclerenchyma cells is strictly controlled by a complex network of transcription factors in vascular plants. However, little is known about the epigenetic mechanism regulating secondary wall biosynthesis. In this study, we identified that ARABIDOPSIS HOMOLOG of TRITHORAX1 (ATX1), a H3K4-histone methyltransferase, mediates the regulation of fiber cell wall development in inflorescence stems of Arabidopsis thaliana. Genome-wide analysis revealed that the up-regulation of genes involved in secondary wall formation during stem development is largely coordinated by increasing level of H3K4 tri-methylation. Among all histone methyltransferases for H3K4me3 in Arabidopsis, ATX1 is markedly increased during the inflorescence stem development and loss-of-function mutant atx1 was impaired in secondary wall thickening in interfascicular fibers. Genetic analysis showed that ATX1 positively regulates secondary wall deposition through activating the expression of secondary wall NAC master switch genes, SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1) and NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1). We further identified that ATX1 directly binds the loci of SND1 and NST1, and activates their expression by increasing H3K4me3 levels at these loci. Taken together, our results reveal that ATX1 plays a key role in the regulation of secondary wall biosynthesis in interfascicular fibers during inflorescence stem development of Arabidopsis.
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http://dx.doi.org/10.1093/nar/gkaa1191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797065PMC
January 2021

Speckle-tracking imaging for pre-excitation cardiomyopathy.

Acta Cardiol 2021 Jun 17;76(4):446-448. Epub 2020 Dec 17.

Department of Ultrasound diagnosis, Children's Hospital of Hebei Province, Shijiazhuang, China.

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http://dx.doi.org/10.1080/00015385.2020.1841972DOI Listing
June 2021

TLR9 deficiency alleviates doxorubicin-induced cardiotoxicity via the regulation of autophagy.

J Cell Mol Med 2020 09 9;24(18):10913-10923. Epub 2020 Aug 9.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Doxorubicin is a commonly used anthracycline chemotherapeutic drug. Its application for treatment has been impeded by its cardiotoxicity as it is detrimental and fatal. DNA damage, cardiac inflammation, oxidative stress and cell death are the critical links in DOX-induced myocardial injury. Previous studies found that TLR9-related signalling pathways are associated with the inflammatory response of cardiac myocytes, mitochondrial dysfunction and cardiomyocyte death, but it remains unclear whether TLR9 could influence DOX-induced heart injury. Our current data imply that DOX-induced cardiotoxicity is ameliorated by TLR9 deficiency both in vivo and in vitro, manifested as improved cardiac function and reduced cardiomyocyte apoptosis and oxidative stress. Furthermore, the deletion of TLR9 rescued DOX-induced abnormal autophagy flux in vivo and in vitro. However, the inhibition of autophagy by 3-MA abolished the protective effects of TLR9 deletion on DOX-induced cardiotoxicity. Moreover, TLR9 ablation suppressed the activation of p38 MAPK during DOX administration and may promote autophagy via the TLR9-p38 MAPK signalling pathway. Our study suggests that the deletion of TLR9 exhibits a protective effect on doxorubicin-induced cardiotoxicity by enhancing p38-dependent autophagy. This finding could be used as a basis for the development of a prospective therapy against DOX-induced cardiotoxicity.
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http://dx.doi.org/10.1111/jcmm.15719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521247PMC
September 2020

Critical roles of macrophages in pressure overload-induced cardiac remodeling.

J Mol Med (Berl) 2021 01 31;99(1):33-46. Epub 2020 Oct 31.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.

Macrophages are integral components of the mammalian heart that show extensive expansion in response to various internal or external stimuli. After the onset of sustained pressure overload (PO), the accumulation of cardiac macrophages through local macrophage proliferation and monocyte migration has profound effects on the transition to cardiac hypertrophy and remodeling. In this review, we describe the heterogeneity and diversity of cardiac macrophages and summarize the current understanding of the important roles of macrophages in PO-induced cardiac remodeling. In addition, the possible mechanisms involved in macrophage modulation are also described. Finally, considering the significant effects of cardiac macrophages, we highlight their emerging role as therapeutic targets for alleviating pathological cardiac remodeling after PO.
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http://dx.doi.org/10.1007/s00109-020-02002-wDOI Listing
January 2021

Weaving public health and safety nets to respond the COVID-19 pandemic.

Saf Sci 2021 Feb 22;134:105058. Epub 2020 Oct 22.

Center of Excellence in Risk & Decision Sciences, European University Cyprus, Nicosia 2404, Cyprus.

How do governments take strategic actions in weaving public health and safety nets to respond to the COVID-19 pandemic? Embracing Moore's strategic action framework, this study investigates how municipal governments can configure authorizing environment-operational capacity-public value attributes to weave public health and safety nets, in order to prevent and control the public health and safety emergency. Leveraging fuzzy-set Qualitative Comparative Analysis (fsQCA) with a sample of 323 Chinese cities, we identify a distinctive taxonomy of four equally effective configurations of urban actions in blocking COVID-19 transmission: , , , and . Overall, this study provides a novel insight of public health and safety management into battles against COVID-19 in human society.
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http://dx.doi.org/10.1016/j.ssci.2020.105058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580673PMC
February 2021

Eye Gaze Based 3D Triangulation for Robotic Bionic Eyes.

Sensors (Basel) 2020 Sep 15;20(18). Epub 2020 Sep 15.

Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China.

Three-dimensional (3D) triangulation based on active binocular vision has increasing amounts of applications in computer vision and robotics. An active binocular vision system with non-fixed cameras needs to calibrate the stereo extrinsic parameters online to perform 3D triangulation. However, the accuracy of stereo extrinsic parameters and disparity have a significant impact on 3D triangulation precision. We propose a novel eye gaze based 3D triangulation method that does not use stereo extrinsic parameters directly in order to reduce the impact. Instead, we drive both cameras to gaze at a 3D spatial point at the optical center through visual servoing. Subsequently, we can obtain the 3D coordinates of through the intersection of the two optical axes of both cameras. We have performed experiments to compare with previous disparity based work, named the integrated two-pose calibration (ITPC) method, using our robotic bionic eyes. The experiments show that our method achieves comparable results with ITPC.
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http://dx.doi.org/10.3390/s20185271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571035PMC
September 2020

The Roles of Noncardiomyocytes in Cardiac Remodeling.

Int J Biol Sci 2020 2;16(13):2414-2429. Epub 2020 Jul 2.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, RP China.

Cardiac remodeling is a common characteristic of almost all forms of heart disease, including cardiac infarction, valvular diseases, hypertension, arrhythmia, dilated cardiomyopathy and other conditions. It is not merely a simple outcome induced by an increase in the workload of cardiomyocytes (CMs). The remodeling process is accompanied by abnormalities of cardiac structure as well as disturbance of cardiac function, and emerging evidence suggests that a wide range of cells in the heart participate in the initiation and development of cardiac remodeling. Other than CMs, there are numerous noncardiomyocytes (non-CMs) that regulate the process of cardiac remodeling, such as cardiac fibroblasts and immune cells (including macrophages, lymphocytes, neutrophils, and mast cells). In this review, we summarize recent knowledge regarding the definition and significant effects of various non-CMs in the pathogenesis of cardiac remodeling, with a particular emphasis on the involved signaling mechanisms. In addition, we discuss the properties of non-CMs, which serve as targets of many cardiovascular drugs that reduce adverse cardiac remodeling.
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http://dx.doi.org/10.7150/ijbs.47180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378633PMC
July 2020

The artemisinin analog SM934 alleviates dry eye disease in rodent models by regulating TLR4/NF-κB/NLRP3 signaling.

Acta Pharmacol Sin 2021 Apr 3;42(4):593-603. Epub 2020 Aug 3.

Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Dry eye disease (DED) is a multifactorial disorder of the tears and ocular surface characterized by manifestations of dryness and irritation. Although the pathogenesis is not fully illuminated, it is recognized that inflammation has a prominent role in the development and deterioration of DED. β-aminoarteether maleate (SM934) is a water-soluble artemisinin derivative with anti-inflammatory and immunosuppressive activities. In this study, we established scopolamine hydrobromide (SCOP)-induced rodent model as well as benzalkonium chloride (BAC)-induced rat model to investigate the therapeutic potential of SM934 for DED. We showed that topical application of SM934 (0.1%, 0.5%) significantly increased tear secretion, maintained the number of conjunctival goblet cells, reduced corneal damage, and decreased the levels of inflammatory mediators (TNF-α, IL-6, IL-10, or IL-1β) in conjunctiva in SCOP-induced and BAC-induced DED models. Moreover, SM934 treatment reduced the accumulation of TLR4-expressing macrophages in conjunctiva, and suppressed the expression of inflammasome components, i.e., myeloid differentiation factor88 (MyD88), Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), and cleaved caspase 1. In LPS-treated RAW 264.7 cells, we demonstrated that pretreatment with SM934 (10 μM) impeded the upregulation of TLR4 and downstream NF-κB/NLRP3 signaling proteins. Collectively, artemisinin analog SM934 exerts therapeutic benefits on DED by simultaneously reserving the structural integrity of ocular surface and preventing the corneal and conjunctival inflammation, suggested a further application of SM934 in ophthalmic therapy, especially for DED.
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http://dx.doi.org/10.1038/s41401-020-0484-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114933PMC
April 2021

Plant endophytes promote growth and alleviate salt stress in Arabidopsis thaliana.

Sci Rep 2020 07 29;10(1):12740. Epub 2020 Jul 29.

Department of Plant Science, McGill University, Macdonald Campus, 21111 Lakeshore Road, Sainte-Anne-de-Bellevue, Québec, H9X 3V9, Canada.

Plant growth promoting rhizobacteria (PGPR) are a functionally diverse group of microbes having immense potential as biostimulants and stress alleviators. Their exploitation in agro-ecosystems as an eco-friendly and cost-effective alternative to traditional chemical inputs may positively affect agricultural productivity and environmental sustainability. The present study describes selected rhizobacteria, from a range of origins, having plant growth promoting potential under controlled conditions. A total of 98 isolates (ectophytic or endophytic) from various crop and uncultivated plants were screened, out of which four endophytes (n, L, K and Y) from Phalaris arundinacea, Solanum dulcamara, Scorzoneroides autumnalis, and Glycine max, respectively, were selected in vitro for their vegetative growth stimulating effects on Arabidopsis thaliana Col-0 seedlings with regard to leaf surface area and shoot fresh weight. A 16S rRNA gene sequencing analysis of the strains indicated that these isolates belong to the genera Pseudomonas, Bacillus, Mucilaginibacter and Rhizobium. Strains were then further tested for their effects on abiotic stress alleviation under both Petri-plate and pot conditions. Results from Petri-dish assay indicated strains L, K and Y alleviated salt stress in Arabidopsis seedlings, while strains K and Y conferred increases in fresh weight and leaf area under osmotic stress. Results from subsequent in vivo trials indicated all the isolates, especially strains L, K and Y, distinctly increased A. thaliana growth under both normal and high salinity conditions, as compared to control plants. The activity of antioxidant enzymes (ascorbate peroxidase, catalase and peroxidase), proline content and total antioxidative capacity also differed in the inoculated A. thaliana plants. Furthermore, a study on spatial distribution of the four strains, using either conventional Petri-plate counts or GFP-tagged bacteria, indicated that all four strains were able to colonize the endosphere of A. thaliana root tissue. Thus, the study revealed that the four selected rhizobacteria are good candidates to be explored as plant growth stimulators, which also possess salt stress mitigating property, partially by regulating osmolytes and antioxidant enzymes. Moreover, the study is the first report of Scorzoneroides autumnalis (fall dandelion) and Solanum dulcamara (bittersweet) associated endophytes with PGP effects.
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http://dx.doi.org/10.1038/s41598-020-69713-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391687PMC
July 2020

Lnc00462717 regulates the permeability of the blood-brain tumor barrier through interaction with PTBP1 to inhibit the miR-186-5p/Occludin signaling pathway.

FASEB J 2020 08 5;34(8):9941-9958. Epub 2020 Jul 5.

Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, P.R. China.

Blood-brain tumor barrier (BTB) severely restricts the efficient delivery of chemotherapeutic drugs into brain tumor tissue, which is a critical obstacle for glioma treatment. Recently, long noncoding RNAs (lncRNAs) have shown as regulation factors of numerous biological processes. In this study, we identified that Lnc00462717 was upregulated in glioma endothelial cells (GECs), and that knockdown of Lnc00462717 significantly increased the BTB permeability. Both bioinformatics and RNA immunoprecipitation (RIP) results revealed that Lnc00462717 interacts with polypyrimidine tract binding protein (PTBP1). Moreover, overexpression of PTBP1 significantly reversed the increase in BTB permeability caused by siLnc00462717. Furthermore, the binding sites between miR-186 and PTBP1 as well as between miR-186 and 3'UTR of Occludin mRNA were confirmed by RIP and luciferase assays, respectively. And the interaction of Lnc00462717 and PTBP1 significantly facilitated the binding of PTBP1 to 3'UTR of Occludin mRNA and then blocked the miR-186-5p-induced downregulation of Occludin. In addition, we identified that knockdown of Lnc00462717 or overexpression of miR-186-5p increased the accumulation of doxorubicin (Dox) in brain glioma via the ultrafast liquid chromatography-mass spectrometry system (UFLC-MS/MS system) and decreased the intracranial glioma volume in BALB/c nude mice. Taken together, these results show a novel molecular pathway in BTB that may provide a potential innovative strategy for glioma therapy.
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http://dx.doi.org/10.1096/fj.202000045RDOI Listing
August 2020

MiR319a-targeted PtoTCP20 regulates secondary growth via interactions with PtoWOX4 and PtoWND6 in Populus tomentosa.

New Phytol 2020 11 31;228(4):1354-1368. Epub 2020 Jul 31.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, 100871, China.

Secondary growth is a key characteristic of trees, which requires the coordination of multiple regulatory mechanisms including transcriptional regulators and microRNAs (miRNAs). However, the roles of microRNAs in the regulation of secondary growth need to be explored in depth. Here, the role of miR319a and its target, PtoTCP20, in the secondary growth of Populus tomentosa stem was investigated using genetic and molecular analyses. The expression level of miR319a gradually decreased from primary to secondary growth in P. tomentosa, while that of PtoTCP20 gradually increased. MiR319a overexpression in seedlings resulted in delayed secondary growth and decreased xylem production, while miR319a knockdown and PtoTCP20 overexpression promoted secondary growth and increased xylem production. Further analysis showed that PtoTCP20 interacted with PtoWOX4a and activated PtoWND6 transcription in vitro and in vivo. Our data show that PtoTCP20 controls vascular cambium proliferation by binding to PtoWOX4a, and promotes secondary xylem differentiation by activating PtoWND6 transcription, thereby regulating secondary growth in P. tomentosa. Our findings provide insight into the molecular mechanisms underlying secondary growth in trees.
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http://dx.doi.org/10.1111/nph.16782DOI Listing
November 2020

Drug-internalized bacterial swimmers for magnetically manipulable tumor-targeted drug delivery.

Nanoscale 2020 Jul;12(25):13513-13522

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China. and Laboratory of Theoretical and Computational Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China and University of Chinese Academy of Sciences, Beijing 100049, China and Sino-Danish Center for Education and Research, Beijing 101408, China and Beijing Key Laboratory of Ambient Particles Health Effects and Prevention Techniques, National Center for Nanoscience and Technology, Beijing 100190, China.

Tumor-targeted drug carriers are becoming attractive for precise drug delivery in anti-tumor therapy. However, a lot of the reported drug delivery systems are complicatedly designed and their destiny in vivo is beyond our control, which limited their clinical applications. Hence, it is urgently needed to develop spatio-manipulable self-propelled nanosystems for drug delivery in a facile way. Here, we have successfully constructed drug-internalized bacterial swimmers, whose movement can be manually controlled by an external magnetic field (MF). We demonstrate that the swimmers maintain the mobility to align and swim along MF lines. Further studies reveal that the doxorubicin (DOX-) internalized bacterial swimmers are able to navigate toward tumor sites under the guidance of MF, rendering enhanced anti-tumor efficacy compared with that of dead ones and free DOX. Therefore, the MF-guided bacterial swimmers hold great promise for spatio-manipulable drug delivery in precision medicine.
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http://dx.doi.org/10.1039/d0nr01892aDOI Listing
July 2020

Multimodal Imaging of Cerebral Microhemorrhages and White Matter Degradation in Geriatric Patients with Mild Traumatic Brain Injury.

Methods Mol Biol 2020 ;2144:223-236

Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.

Traditionally, neurobiologists have utilized microscale techniques of scientific investigation to uncover the fundamental organization and function of brain cells and neuronal ensembles. In recent decades, however, macroscale brain imaging methods like magnetic resonance imaging (MRI) and computed tomography (CT) have facilitated a wider scope of understanding neural structure and function across the lifespan. Thanks to such methods, a broader picture of the relationship between microscale processes-studied by neurobiologists-and macroscale observations-made by clinicians-has emerged. More recently, the vascular component of neurodegeneration has come under renewed scrutiny partly due to increased appreciation of the relationship between neurovascular injury, cardiovascular disease, and senescence. Cerebral microbleeds (CMBs) are among the smallest lesions of the cerebrum which can be visualized using MRI to indicate blood-brain barrier (BBB) impairment; as such, this class of hemorrhages are important for the evaluation and macroscale detection of geriatric patients' microscale pathologies associated with neurovascular disease and/or neurodegeneration. This chapter details a streamlined protocol for MRI/CT multimodal imaging data acquisition, archiving and digital processing, including methods tailored for the analysis of susceptibility-weighted imaging (SWI) and diffusion-weighted imaging (DWI) scans to reveal CMB-related alterations of the human connectome. Efficient and effective MRI/CT methods like ours, when tailored for CMB and connectome analysis, are essential for future progress in this important field of scientific inquiry.
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http://dx.doi.org/10.1007/978-1-0716-0592-9_20DOI Listing
March 2021

Nitric oxide affects cisplatin cytotoxicity oppositely in A2780 and A2780-CDDP cells via the connexin32/gap junction.

Cancer Sci 2020 Aug 17;111(8):2779-2788. Epub 2020 Jun 17.

Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Chemoresistance is a main obstacle in ovarian cancer therapy and new treatment strategies and further information regarding the mechanism of the medication cisplatin are urgently needed. Nitric oxide has a critical role in modulating the activity of chemotherapeutic drugs. Our previous work showed that connexin32 contributed to cisplatin resistance. However, whether nitric oxide is involved in connexin32-mediated cisplatin resistance remains unknown. In this study, using A2780 and A2780 cisplatin-resistant cells, we found that S-nitroso-N-acetyl-penicillamine, a nitric oxide donor, attenuated cisplatin toxicity by decreasing gap junctions in A2780 cells. Enhancement of gap junctions using retinoic acid reversed the effects of S-nitroso-N-acetyl-penicillamine on cisplatin toxicity. In A2780 cisplatin-resistant cells, however, S-nitroso-N-acetyl-penicillamine enhanced cisplatin toxicity by decreasing connexin32 expression. Downregulation of connexin32 expression by small interfering RNA exacerbated the effects of S-nitroso-N-acetyl-penicillamine on cisplatin cytotoxicity and upregulation of connexin32 expression by pcDNA transfection reversed the effects of S-nitroso-N-acetyl-penicillamine on cisplatin cytotoxicity. Our study suggests for the first time that combining cisplatin with nitric oxide in clinical therapies for ovarian cancer should be avoided before cisplatin resistance emerges. The present study provides a productive area of further study for increasing the efficacy of cisplatin by combining cisplatin with the specific inhibitors or enhancers of nitric oxide in clinical treatment.
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http://dx.doi.org/10.1111/cas.14436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419057PMC
August 2020

miR319a/TCP module and DELLA protein regulate trichome initiation synergistically and improve insect defenses in Populus tomentosa.

New Phytol 2020 08 12;227(3):867-883. Epub 2020 May 12.

Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation, School of Life Sciences, Southwest University, Chongqing, 400715, China.

Trichomes are specialized epidermal cells that contribute to plant resistance against herbivores. Their formation is controlled precisely by multiple genetic and environmental signals. Previous studies have shown that microRNA319 (miR319) and gibberellin (GA) signaling are involved in trichome development in Arabidopsis, but little is known about their interaction between these factors. Here we reported that the miR319a/TEOSINTE BRANCHED/CYCLOIDEA/PCF (TCP) module participates in trichome initiation synergistically with GA signaling in Populus tomentosa. We demonstrated that overexpression of miR319a decreased transcription levels of its targeted TCPs and significantly elevated leaf trichome density in transgenic poplar, resulting in decreasing insect herbivory. Conversely, repressing miR319a by short tandem target mimics (STTM) elevated TCP expression levels and decreased trichome density in transgenic plants. The trichome phenotype of 35S:miR319a plants could be abolished by introducing a miR319a-resistant form of TCP19. Furthermore, the miR319a-targeted TCP19 interacted directly with REPRESSOR OF ga1-3 (RGA), a downstream repressor of GA signaling. TCP19 and RGA synergistically inhibited the GLABROUS1 (GL1)-induced expression of trichome marker gene GLABRA2 (GL2), thereby repressing leaf trichome initiation. Our results provide an insight into the molecular mechanism by which miR319/TCP19 module and GA signaling coordinated regulating trichome initiation in P. tomentosa.
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http://dx.doi.org/10.1111/nph.16585DOI Listing
August 2020
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