Publications by authors named "Hong Fan"

465 Publications

Can YKL-40 be used as a biomarker for interstitial lung disease?: A systematic review and meta-analysis.

Medicine (Baltimore) 2021 Apr;100(17):e25631

Department of Respiratory Medicine and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University.

Background: Interstitial lung disease (ILD) has a poor prognosis and lacks specific biomarkers for early diagnosis, assessment of disease severity, and prognosis. YKL-40 levels were found to be elevated in patients with ILD, but these results are inconsistent. Therefore, we conducted a systematic review and meta-analysis to accurately study the relation between YKL-40 and ILD.

Methods: We performed a systematic literature search in many databases (PubMed, Embase, the China National Knowledge Infrastructure, and Wanfang databases) and commercial Internet search engines to identify studies involving the role of YKL-40 in patients with ILD. The weighted mean difference with its 95% confidence interval were used to investigate the effect sizes. If obvious heterogeneity was found in the meta-analysis, the level of YKL-40 was directly compared by the Mann-Whitney test.

Results: Sixteen eligible articles were finally identified. The results showed that the serum YKL-40 levels of patients with idiopathic pulmonary fibrosis, connective tissue-related ILD, sarcoidosis, cryptogenic tissue pneumonia, asbestosis-ILD, and idiopathic nonspecific interstitial pneumonia were higher than those in controls, but there was no increase in patients with pulmonary alveolar proteinosis. We also found that there are certain differences in the serum YKL-40 levels in patients with different types of ILD. The results showed that the bronchoalveolar lavage fluid YKL-40 levels of patients with idiopathic pulmonary fibrosis were significantly higher than that in controls. A systematic review indicated that there were correlations between the serum YKL-40 levels and lung function in patients with different ILD. In addition, YKL-40 may be used as a valuable biomarker for survival, with risk ratios ranging from 1.006 to 10.9.

Conclusions: This study suggests that YKL-40 may be a useful biomarker for the diagnosis and prognosis of ILD.
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http://dx.doi.org/10.1097/MD.0000000000025631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083999PMC
April 2021

No Tillage With Plastic Re-mulching Maintains High Maize Productivity Regulating Hydrothermal Effects in an Arid Region.

Front Plant Sci 2021 9;12:649684. Epub 2021 Apr 9.

Department of Biological Systems Engineering, Washington State University, Pullman, WA, United States.

Plastic is a valuable mulching measure for increasing crop productivity in arid environments; however, little is known about the main mechanism by which this valuable technology actuates spatial-temporal changes in soil hydrothermal effect. So a 3-year field experiment was conducted to optimize soil hydrothermal effect of maize field with three plastic mulched management treatments: (1) no tillage with plastic re-mulching (NM), (2) reduced tillage with plastic mulching (RM), and (3) conventional tillage with annual new plastic mulching (CM). The results showed that NM treatment increased soil water content by 6.6-8.4% from maize sowing to seedling stage, than did CM, and it created a good soil moisture environment for sowing of maize. Also, NM had greater soil water content by 4.8-5.6% from maize silking to early-filling stage than had CM, and it made up for the abundant demand of soil moisture for the vigorous growth of maize filling stage. The NM treatment increased water consumption (WC) before maize big-flare stage, decreased WC from big-flare to early-filling stage, and increased WC after early-filling stage. So NM treatment effectively coordinated water demand contradiction of maize at entire growing season. NM decreased soil accumulated temperature (SAT) by 7.0-13.0% at maize sowing to early-filling stage than did CM, but NM had little influence on the SAT during filling stage. In particular, the treatment on NM had smaller absolute values of air-soil temperature differences than RM and CM treatments during maize filling stage, indicating that NM treatment maintains the relative stability of soil temperature for ensuring grain filling of maize. The NM treatment allowed the maize to grow in a suitable hydrothermal status and still maintained high yield. In addition, NM treatment obtained higher net income and rate of return by 6.4-11.0% and 44.1-54.5%, respectively, than did CM, because NM treatment mainly decreased the input costs for plastic and machine operations. Therefore, the NM treatment can be recommended as a promising technique to overcome simultaneous heat stress and water shortage in arid environments.
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http://dx.doi.org/10.3389/fpls.2021.649684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062785PMC
April 2021

Hypoxia inducible factor-1α cooperates with histone Lys methylation to predict prognosis in esophageal squamous cell carcinoma.

Biomark Med 2021 Apr 15. Epub 2021 Apr 15.

Department of Medical Genetics & Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes & Human Diseases, Ministry of Education, Southeast University, Nanjing, 210009, China.

To investigate hypoxia inducible factor-1α (HIF-1α) and histone methylation markers as potential indicators of prognosis in esophageal squamous cell carcinoma (ESCC). The prognostic value of HIF-1α and histone methylation markers levels was analyzed using Kaplan-Meier survival analysis. HIF-1α protein expression was higher in ESCC tumors than in paracancerous tissues. Histone H3 Lys9 trimethylation (H3K9me3), histone H3 Lys27 trimethylation (H3K27me3), histone H3 Lys4 trimethylation (H3K4me3) and histone H4 Lys20 trimethylation (H4K20me3) were significantly upregulated in ESCC tissues. HIF-1α was only positively correlated with H3K9me3 and H3K4me3 expression. Kaplan-Meier analysis indicated that H3K9me3, H3K27me3, H4K20me3 and histone H3 Lys36 trimethylation (H3K36me3) were independent indicators of prognosis for ESCC. This study identified a pattern of epigenetic methylation markers and HIF-1α expression in ESCC, and their combined evaluation might improve survival prediction for ESCC patients.
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http://dx.doi.org/10.2217/bmm-2020-0256DOI Listing
April 2021

TRERNA1 upregulation mediated by HBx promotes sorafenib resistance and cell proliferation in HCC via targeting NRAS by sponging miR-22-3p.

Mol Ther 2021 Apr 9. Epub 2021 Apr 9.

Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, China. Electronic address:

Hepatocellular carcinoma (HCC) is among the most common malignancies and has an unfavorable prognosis. The hepatitis B virus-encoded X (HBx) protein is closely associated with hepatocarcinogenesis. Sorafenib is a unique targeted oral kinase inhibitor for advanced HCC. Long noncoding RNAs (lncRNAs) mediate HCC progression and therapeutic resistance by acting as competing endogenous RNAs (ceRNAs). However, the ceRNA regulatory mechanisms underlying sorafenib resistance in HBx-associated HCC remain largely unknown. In this study, we found that translation regulatory lncRNA 1 (TRERNA1) upregulation by HBx not only promoted HCC cell proliferation by regulating the cell cycle in vitro and in vivo but also correlated positively with poor prognosis in HCC. Importantly, TRERNA1 enhanced sorafenib resistance in HCC cells. RNA sequencing (RNA-seq) analysis indicated that NRAS proto-oncogene (NRAS) is a potential target of TRERNA1 that mediates aspects of hepatocellular carcinogenesis. TRERNA1 acts as a ceRNA to regulate NRAS expression by sponging microRNA (miR)-22-3p. In summary, we show that increased TRERNA1 expression induced by HBx reduces HCC cell sensitivity to sorafenib by activating the RAS/Raf/MEK/ERK signaling pathway. We reveal a novel regulatory mode by which the TRERNA1/miR-22-3p/NRAS axis mediates HCC progression and indicates that TRERNA1 might constitute a powerful tumor biomarker and therapeutic target in HCC.
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http://dx.doi.org/10.1016/j.ymthe.2021.04.011DOI Listing
April 2021

KDM3B-ETF1 fusion gene downregulates LMO2 via the WNT/β-catenin signaling pathway, promoting metastasis of invasive ductal carcinoma.

Cancer Gene Ther 2021 Apr 7. Epub 2021 Apr 7.

Department of Pathology, Henan Provincial People's Hospital, Zhengzhou, PR China.

Breast cancer is the most common malignancy for women, with invasive ductal carcinoma being the largest subtype of breast cancers, accounting for 75-80% of cases. However, the underlying mechanism of invasive ductal carcinoma remains unclear. In this study, we investigate the possible effects KDM3B-ETF1 fusion gene has on breast cancer cell metastasis, invasion and its downstream signaling mediators as revealed from RNA sequence data analysis. As predicted, KDM3B-ETF1 expression was increased in breast cancer tissues and cells. Overexpression of KDM3B-ETF1 in cancer cell lines promoted the growth and invasion of breast cancer cells, while KDM3B-ETF1 knockdown showed the opposite effects on malignant cell growth and invasion both in vivo and in vitro as evidenced by cell counting kit-8, Transwell assay and tumor xenograft in nude mice. On the contrary, LIM Domain Only 2 (LMO2) expression was significantly reduced in breast cancer tissues and cells. According to chromatin immunoprecipitation and Western blot analysis, KDM3B-ETF1 targets LMO2 and reduced the expression of LMO2, leading to an increase in WNT/β-catenin signaling pathway and thus promoting invasion. In conclusion, fusion gene KDM3B-ETF1 inhibits LMO2, activates the Wnt/β-catenin signaling pathway that leads to increased breast cancer cell invasion and metastasis, providing a novel insight into developing therapeutic strategies. These results provide novel insights into the molecular mechanism of invasive ductal carcinomas, which may lead to potential therapeutic targets.
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http://dx.doi.org/10.1038/s41417-021-00301-zDOI Listing
April 2021

Multi-omics characterization and validation of invasiveness-related molecular features across multiple cancer types.

J Transl Med 2021 03 25;19(1):124. Epub 2021 Mar 25.

Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, China.

Background: Tumor invasiveness reflects many biological changes associated with tumorigenesis, progression, metastasis, and drug resistance. Therefore, we performed a systematic assessment of invasiveness-related molecular features across multiple human cancers.

Materials And Methods: Multi-omics data, including gene expression, miRNA, DNA methylation, and somatic mutation, in approximately 10,000 patients across 30 cancer types from The Cancer Genome Atlas, Gene Expression Omnibus, PRECOG, and our institution were enrolled in this study.

Results: Based on a robust gene signature, we established an invasiveness score and found that the score was significantly associated with worse prognosis in almost all cancers. Then, we identified common invasiveness-associated dysregulated molecular features between high- and low-invasiveness score group across multiple cancers, as well as investigated their mutual interfering relationships thus determining whether the dysregulation of invasiveness-related genes was caused by abnormal promoter methylation or miRNA expression. We also analyzed the correlations between the drug sensitivity data from cancer cell lines and the expression level of 685 invasiveness-related genes differentially expressed in at least ten cancer types. An integrated analysis of the correlations among invasiveness-related genetic features and drug response were conducted in esophageal carcinoma patients to outline the complicated regulatory mechanism of tumor invasiveness status in multiple dimensions. Moreover, functional enrichment suggests the invasiveness score might serve as a predictive biomarker for cancer patients receiving immunotherapy.

Conclusion: Our pan-cancer study provides a comprehensive atlas of tumor invasiveness and may guide more precise therapeutic strategies for tumor patients.
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http://dx.doi.org/10.1186/s12967-021-02773-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995758PMC
March 2021

Enlarging the π-Conjugation of Cobalt Porphyrin for Highly Active and Selective CO Electroreduction.

ChemSusChem 2021 Mar 22. Epub 2021 Mar 22.

School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore, 637459, Singapore.

Heterogeneous molecular catalysts have attracted considerable attention as carbon dioxide reduction reaction (CO RR) electrocatalysts. The π-electron system of conjugated ligands in molecular catalysts may play an important role in determining the activity. In this work, by enlarging π-conjugation through appending more aromatic substituents on the porphyrin ligand, altered π-electron system endows the as-prepared 5,10,15,20-tetrakis(4-(pyren-1-yl)phenyl)porphyrin Co with high Faradaic efficiency (ca. 95 %) for CO production, as well as high turnover frequency (2.1 s at -0.6 V vs. RHE). Density functional theory calculation further suggests that the improved electrocatalytic performance mainly originates from the higher proportion of Co orbital and the CO π* orbital in the HOMO of the (Co-porphyrin-CO ) intermediate with larger π-conjugation, which facilitates the CO activation. This work provides strong evidence that π-conjugation perturbation is effective in boosting the CO RR.
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http://dx.doi.org/10.1002/cssc.202100176DOI Listing
March 2021

Regulating DNA Self-Assembly Dynamics with Controlled Nucleation.

ACS Nano 2021 03 11;15(3):5384-5396. Epub 2021 Mar 11.

Center for Molecular Design and Biomimetics at the Biodesign Institute, and School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287, United States.

Controlling the nucleation step of a self-assembly system is essential for engineering structural complexity and dynamic behaviors. Here, we design a "frame-filling" model system that comprises one type of self-complementary DNA tile and a hosting DNA origami frame to investigate the inherent dynamics of three general nucleation modes in nucleated self-assembly: unseeded, facet, and seeded nucleation. Guided by kinetic simulation, which suggested an optimal temperature range to differentiate the individual nucleation modes, and complemented by single-molecule observations, the transition of tiles from a metastable, monomeric state to a stable, polymerized state through the three nucleation pathways was monitored by Mg-triggered kinetic measurements. The temperature-dependent kinetics for all three nucleation modes were correlated by a "nucleation-growth" model, which quantified the tendency of nucleation using an empirical nucleation number. Moreover, taking advantage of the temperature dependence of nucleation, tile assembly can be regulated externally by the hosting frame. An ultraviolet (UV)-responsive trigger was integrated into the frame to simultaneously control "when" and "where" nucleation started. Our results reveal the dynamic mechanisms of the distinct nucleation modes in DNA tile-based self-assembly and provide a general strategy for controlling the self-assembly process.
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http://dx.doi.org/10.1021/acsnano.1c00027DOI Listing
March 2021

Long non-coding RNA ROR recruits histone transmethylase MLL1 to up-regulate TIMP3 expression and promote breast cancer progression.

J Transl Med 2021 03 2;19(1):95. Epub 2021 Mar 2.

Department of Pathology, Henan Provincial People's Hospital, No. 7, Weiwu Road, Zhengzhou, 450003, Henan, People's Republic of China.

Background: As a significant cause of cancer deaths worldwide, breast cancer continues to be a troublesome malignancy. Long non-coding RNAs (lncRNAs) have been implicated in the development of breast cancer. Abnormal methylation has been associated with unfavorable breast cancer prognosis. Herein, the current study aimed to elucidate the role of lncRNA ROR in breast cancer.

Methods: RT-qPCR was performed to determine whether lncRNA ROR was highly expressed in breast cancer tissues, while lncRNA ROR expression was detected in both the nuclear and cytoplasm of breast cancer cells. MCF-7 cells were subsequently introduced with oe-lncRNA ROR, sh-lncRNA ROR to explore the effects of lncRNA ROR on cell proliferation, invasion and apoptosis.

Results: RIP, RNA pull-down and ChIP assays provided evidence suggesting that lncRNA ROR recruited transmethylase MLL1 to promote H3K4 trimethylation that enhanced TIMP3 transcription. The rescue experiments demonstrated that lncRNA ROR knockdown could inhibit the progression of breast cancer via the downregulation of TIMP3. Finally, the in vivo experiment findings consistently highlighted the suppressive effects of lncRNA ROR silencing on tumor growth.

Conclusion: Taken together, our study demonstrates that silencing of lncRNA ROR inhibits breast cancer progression via repression of transmethylase MLL1 and TIMP3, emphasizing the potential of lncRNA ROR as a novel target against breast cancer.
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http://dx.doi.org/10.1186/s12967-020-02682-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927245PMC
March 2021

First-in-human neuroimaging of soluble epoxide hydrolase using [F]FNDP PET.

Eur J Nucl Med Mol Imaging 2021 Feb 13. Epub 2021 Feb 13.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Purpose: Soluble epoxide hydrolase (sEH) is an enzyme with putative effect on neuroinflammation through its influence on the homeostasis of polyunsaturated fatty acids and related byproducts. sEH is an enzyme that metabolizes anti-inflammatory epoxy fatty acids to the corresponding, relatively inert 1,2-diols. A high availability or activity of sEH promotes vasoconstriction and inflammation in local tissues that may be linked to neuropsychiatric diseases. We developed [F]FNDP to study sEH in vivo with positron emission tomography (PET).

Methods: Brain PET using bolus injection of [F]FNDP followed by emission imaging lasting 90 or 180 min was completed in healthy adults (5 males, 2 females, ages 40-53 years). The kinetic behavior of [F]FNDP was evaluated using a radiometabolite-corrected arterial plasma input function with compartmental or graphical modeling approaches.

Results: [F]FNDP PET was without adverse effects. Akaike information criterion favored the two-tissue compartment model (2TCM) in all ten regions of interest. Regional total distribution volume (V) values from each compartmental model and Logan analysis were generally well identified except for corpus callosum V using the 2TCM. Logan analysis was assessed as the choice model due to stability of regional V values from 90-min data and due to high correlation of Logan-derived regional V values with those from the 2TCM. [F]FNDP binding was higher in human cerebellar cortex and thalamus relative to supratentorial cortical regions, which aligns with reported expression patterns of the epoxide hydrolase 2 gene in human brain.

Conclusion: These data support further use of [F]FNDP PET to study sEH in human brain.
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http://dx.doi.org/10.1007/s00259-021-05231-4DOI Listing
February 2021

Integrative genome-scale analysis of immune infiltration in esophageal carcinoma.

Int Immunopharmacol 2021 Apr 31;93:107371. Epub 2021 Jan 31.

Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

To explore the molecular mechanism in the esophageal squamous carcinoma (ESCC) environment, we selected datasets of ESCC patients from The Cancer Genome Atlas (TCGA) (n = 78) and explored the infiltration condition of 24 immune cells in each sample. We assorted the microenvironment of ESCC into two Infiltration groups (I and II) and built a random forest classifier model. We showed traits of gene and clinicopathology in the tumor microenvironment (TME) phenotypes systematically. Infiltration I had low infiltration of immune cells and immunomodulators but relatively higher mutation load, while Infiltration II was enriched with cytotoxic T cells and immunosuppressive cells. The upregulation of several immune cytokines like IFN-γ, TNF-β, and PD-L1 was seen in Infiltration II. The infiltration group was an independent predictor of prognosis showed by Multivariable Cox analysis (Infiltration II vs. I, hazard ratio = 2.73, 95% confidence interval = 1.08-6.91, p = 0.03). All the results can be verified in datasets from the Gene Expression Omnibus database (GEO) and our institution (n = 98). Our results demonstrate a synthesis of the infiltration pattern of the immune in ESCC. We reveal the mechanism of TME, which may contribute to the progress of immunotherapy for patients with ESCC.
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http://dx.doi.org/10.1016/j.intimp.2021.107371DOI Listing
April 2021

Stink bean () empty pod: a potent natural antidiabetic agent for the prevention of pancreatic and hepatorenal dysfunction in high fat diet/streptozotocin-induced type 2 diabetes in rats.

Arch Physiol Biochem 2021 Jan 31:1-7. Epub 2021 Jan 31.

Faculty of Thai Traditional Medicine, Prince of Songkla University, Hat Yai, Thailand.

The present study investigated the effect of polyphenol-rich extract of (PPS) against pancreatic and hepatorenal dysfunction in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetes. Diabetic rats were treated with PPS (100 and 400 mg/kg) and glibenclamide. The results revealed that diabetic rats displayed marked hyperglycaemia, hyperlipidaemia, hypoinsulinemia as well as alterations in serum renal and kidney function markers. Furthermore, diabetic rats showed significant increase in hepatorenal level of malonaldehyde as well as suppression of antioxidant enzyme activities. Whereas, diabetic rats that received PPS displayed marked attenuation in most of the aforementioned parameters compared to the untreated diabetic rats. Additionally, histological examination revealed restoration of histopathological alterations of the pancreas, liver, and kidney of PPS treated diabetic rats. In conclusion, the results demonstrated that PPS could decrease serum lipids and blood glucose level, enhance insulin level and hepatorenal antioxidant capacity, as well as ameliorate hepatorenal dysfunction in rats.
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http://dx.doi.org/10.1080/13813455.2021.1876733DOI Listing
January 2021

CircularRNA circPARP4 promotes glioblastoma progression through sponging miR-125a-5p and regulating FUT4.

Am J Cancer Res 2021 1;11(1):138-156. Epub 2021 Jan 1.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University Beijing 100070, China.

Circular RNA (circRNA) is a widely expressed non-coding RNA element characterized by a covalently closed continuous loop. Emerging evidence suggests important roles of circRNAs in the pathogenesis of human cancers. However, the functions and underlying mechanisms of circRNAs in glioma remain largely unclear. Previously, our studies uncovered a batch of abnormally expressed circRNAs in glioma tissue, among which circPARP4 was significantly upregulated with the top fold change. Here, we focused on the functional investigation toward circPARP4 in glioblastoma progression and looked for insight into its underlying mechanisms. The results confirmed the elevated expression of circPARP4 in glioma and found its association with glioma pathological grade. Gain- and loss-of-function strategies showed that circPARP4 could obviously promote glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Mechanistically, and studies demonstrated that circPARP4, as a miRNA sponge, directly interacted with miR-125a-5p, which then regulated FUT4 to exert the oncogenic effect on glioma behavior. Our findings illustrate functions of circPARP4 in modulating glioma progression through miR-125a-5p/FUT4 pathway, which provides a novel and potential target for glioma therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840713PMC
January 2021

Tip-Enhanced Electric Field: A New Mechanism Promoting Mass Transfer in Oxygen Evolution Reactions.

Adv Mater 2021 Mar 29;33(9):e2007377. Epub 2021 Jan 29.

Division of Energy and Environment, Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China.

The slow kinetics of oxygen evolution reaction (OER) causes high power consumption for electrochemical water splitting. Various strategies have been attempted to accelerate the OER rate, but there are few studies on regulating the transport of reactants especially under large current densities when the mass transfer factor dominates the evolution reactions. Herein, Ni Fe alloy nanocones arrays (with ≈2 nm surface NiO/NiFe(OH) layer) are adopted to boost the transport of reactants. Finite element analysis suggests that the high-curvature tips can enhance the local electric field, which induces an order of magnitude higher concentration of hydroxide ions (OH ) at the active sites and promotes intrinsic OER activity by 67% at 1.5 V. Experimental results show that a fabricated NiFe nanocone array electrode, with optimized alloy composition, has a small overpotential of 190 mV at 10 mA cm and 255 mV at 500 mA cm . When calibrated by electrochemical surface area, the nanocones electrode outperforms the state-of-the-art OER electrocatalysts. The positive effect of the tip-enhanced local electric field in promoting mass transfer is also confirmed by comparing samples with different tip curvature radii. It is suggested that this local field enhanced OER kinetics is a generic effect to other OER catalysts.
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http://dx.doi.org/10.1002/adma.202007377DOI Listing
March 2021

Ferroelastic-switching-driven large shear strain and piezoelectricity in a hybrid ferroelectric.

Nat Mater 2021 May 11;20(5):612-617. Epub 2021 Jan 11.

School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.

Materials that can produce large controllable strains are widely used in shape memory devices, actuators and sensors, and great efforts have been made to improve the strain output. Among them, ferroelastic transitions underpin giant reversible strains in electrically driven ferroelectrics or piezoelectrics and thermally or magnetically driven shape memory alloys. However, large-strain ferroelastic switching in conventional ferroelectrics is very challenging, while magnetic and thermal controls are not desirable for practical applications. Here we demonstrate a large shear strain of up to 21.5% in a hybrid ferroelectric, CHN(CH)CdCl, which is two orders of magnitude greater than that in conventional ferroelectric polymers and oxides. It is achieved by inorganic bond switching and facilitated by structural confinement of the large organic moieties, which prevents undesired 180° polarization switching. Furthermore, Br substitution can soften the bonds, allowing a sizable shear piezoelectric coefficient (d ≈ 4,830 pm V) at the Br-rich end of the solid solution, CHN(CH)CdBrCl. The electromechanical properties of these compounds suggest their potential in lightweight and high-energy-density devices, and the strategy described here could inspire the development of next-generation piezoelectrics and electroactive materials based on hybrid ferroelectrics.
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http://dx.doi.org/10.1038/s41563-020-00875-3DOI Listing
May 2021

Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence.

Front Pharmacol 2020 14;11:553690. Epub 2020 Dec 14.

Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Chengdu, China.

Idiopathic pulmonary fibrosis is an aging-associated disease, satisfactory therapies are not yet available. Accelerated senescence of alveolar epithelial cells plays an important part in Idiopathic pulmonary fibrosis pathogenesis. Fisetin (FIS) is a natural non-toxic flavonoid, which has many pharmacological functions. However, the role of FIS in pulmonary fibrosis has not been established. In this study, we found that FIS treatment apparently alleviated BLM-induced weight loss, inflammatory cells infiltration, inflammatory factors expression, collagen deposition and alveolar epithelial cell senescence, along with AMPK activation and the down regulation of NF-κB and TGF-β/Smad3 . , FIS administration significantly inhibited the senescence of alveolar epithelial cells and senescence-associated secretory phenotype, followed by reduced transdifferentiation of fibroblasts to myofibroblasts as well as collagen deposition in fibroblasts, which was blocked by an AMPK inhibitor, Compound C. Together, these results suggest that FIS can alleviate the development of BLM-induced pulmonary fibrosis, which is related to the inhibition of TGF-β/Smad3 signaling and the reduction of alveolar epithelium cell senescence by regulating AMPK/NF-κB signaling pathway. FIS may be a promising candidate for patients with pulmonary fibrosis.
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http://dx.doi.org/10.3389/fphar.2020.553690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768023PMC
December 2020

Improved ANFIS model for forecasting Wuhan City Air Quality and analysis COVID-19 lockdown impacts on air quality.

Environ Res 2021 03 17;194:110607. Epub 2020 Dec 17.

Department of Mathematics, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt. Electronic address:

In this study, we propose an improved version of the adaptive neuro-fuzzy inference system (ANFIS) for forecasting the air quality index in Wuhan City, China. We propose a hybrid optimization method to improve ANFIS performance, called PSOSMA, using a new modified meta-heuristics (MH) algorithm, Slime mould algorithm (SMA), which is improved by using the particle swarm optimizer (PSO). The proposed PSOSMA-ANFIS has been trained with air quality index time series data of three years and has been applied to forecast the fine particulate matter (PM2.5), sulfur dioxide (SO2), carbon dioxide (CO2), and nitrogen dioxide (NO2) for one year. We also compared the proposed PSOSMA to other MH algorithms used to train ANFIS. We found that the modified ANFIS using PSOSMA achieved better performance than compared algorithms. Moreover, we analyzed the impacts of the lockdown of Wuhan City on the concentrations of PM2.5, NO2, CO2, and SO2. We compared the correspondence period with previous years, and we concluded that there are significant decreases in the concentrations of PM2.5, CO2, SO2, and NO2.
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http://dx.doi.org/10.1016/j.envres.2020.110607DOI Listing
March 2021

Spermatogonial stem cells are a promising and pluripotent cell source for regenerative medicine.

Am J Transl Res 2020 15;12(11):7048-7059. Epub 2020 Nov 15.

Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University Xi'an 710054, China.

Regenerative medicine has been shown to hold enormous potential to treat traumatic and degenerative diseases, and substantial advancements have been made in the recent decades. In particular, different cell types were evaluated in basic research and preclinical studies on cell-based therapy applications. Despite the extraordinary achievements made in experimental studies and clinical practice, a considerable number of obstacles, such as the cellular source, ethical and safety issues, hinder further clinical applications. Spermatogonial stem cells (SSCs) are gradually becoming the research focus of cell-based regenerative medicine owing to their unique merits over other types of stem cells, particularly the lack of ethical concerns and lower immunogenicity. In addition, SSCs have been successfully induced to differentiate into other cell types under different appropriate conditions in compelling studies. Based on these properties, we systemically reviewed the development of SSCs as an attractive cell source for cell-based regenerative medicine.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724348PMC
November 2020

Exosomal O-GlcNAc transferase from esophageal carcinoma stem cell promotes cancer immunosuppression through up-regulation of PD-1 in CD8 T cells.

Cancer Lett 2021 Mar 8;500:98-106. Epub 2020 Dec 8.

Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. Electronic address:

Esophageal carcinoma stem cells (ECSCs) are responsible for the initiation and therapy-resistance of esophageal cancer. Nutrient sensor O-GlcNAc transferase (OGT) promoted the growth and metastasis of cancer cells. However, the contributions of OGT to the tumorigenesis of ECSCs remain largely uncover. In the present study, as compared to matched non-stem cancer cells, the expression of OGT was higher in ALDH ECSCs. Knock down of OGT by lentivirus system reduced the self-renewal capacities and tumorigenicity of ALDH ECSCs. In addition, OGT in exosome derived from ALDH ECSCs was taken up by neighboring CD8 T cells and increased the expression of PD-1 in CD8 T cells. Down-regulation of OGT increased the apoptosis of ALDH ECSCs induced by CD8 T cells, which could be blocked by overexpression of PD-1 in CD8 T cells. Together, OGT in exosome from ECSCs protects ECSCs from CD8 T cells through up-regulation of PD-1.
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http://dx.doi.org/10.1016/j.canlet.2020.12.012DOI Listing
March 2021

F-labeled radiotracers for in vivo imaging of DREADD with positron emission tomography.

Eur J Med Chem 2021 Mar 25;213:113047. Epub 2020 Nov 25.

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. Electronic address:

Designer Receptors Exclusively Activated by Designer Drugs (DREADD) are a preclinical chemogenetic approach with clinical potential for various disorders. In vivo visualization of DREADDs has been achieved with positron emission tomography (PET) using C radiotracers. The objective of this study was to develop DREADD radiotracers labeled with F for a longer isotope half-life. A series of non-radioactive fluorinated analogs of clozapine with a wide range of in vitro binding affinities for the hM3Dq and hM4Di DREADD receptors has been synthesized for PET. Compound [F]7b was radiolabeled via a modified F-deoxyfluorination protocol with a commercial ruthenium reagent. [F]7b demonstrated encouraging PET imaging properties in a DREADD hM3Dq transgenic mouse model, whereas the radiotracer uptake in the wild type mouse brain was low. [F]7b is a promising long-lived alternative to the DREADD radiotracers [C]clozapine ([C]CLZ) and [C]deschloroclozapine ([C]DCZ).
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http://dx.doi.org/10.1016/j.ejmech.2020.113047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925357PMC
March 2021

An improved deep learning model for predicting daily PM2.5 concentration.

Sci Rep 2020 12 2;10(1):20988. Epub 2020 Dec 2.

State Key Laboratory of Information Engineering in Surveying, Mapping and Remote Sensing, Wuhan University, 129 Luoyu Road, Wuhan, 430079, China.

Over the past few decades, air pollution has caused serious damage to public health. Therefore, making accurate predictions of PM2.5 is a crucial task. Due to the transportation of air pollutants among areas, the PM2.5 concentration is strongly spatiotemporal correlated. However, the distribution of air pollution monitoring sites is not even making the spatiotemporal correlation between the central site and surrounding sites vary with different density of sites, and this was neglected by previous methods. To this end, this study proposes a weighted long short-term memory neural network extended model (WLSTME), which addressed the issue that how to consider the effect of the density of sites and wind conditions on the spatiotemporal correlation of air pollution concentration. First, a number of nearest surrounding sites were chosen as the neighbor sites to the central site, and their distance, as well as their air pollution concentration and wind condition, were input to multilayer perception (MLP) to generate weighted historical PM2.5 time series data. Second, historical PM2.5 concentration of the central site and weighted PM2.5 series data of neighbor sites were input into a long short-term memory (LSTM) to address spatiotemporal dependency simultaneously and extract spatiotemporal features. Finally, another MLP was utilized to integrate spatiotemporal features extracted above with the meteorological data of the central site to generate the forecasts future PM2.5 concentration of the central site. Daily PM2.5 concentration and meteorological data on Beijing-Tianjin-Hebei from 2015 to 2017 were collected to train models and to evaluate its performance. Experimental results with three existing methods showed that the proposed WLSTME model has the lowest RMSE (40.67) and MAE (26.10) and the highest p (0.59). Further experiments showed that in all seasons and regions, WLSTME performed the best. This finding confirms that WLSTME can significantly improve PM2.5 prediction accuracy.
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http://dx.doi.org/10.1038/s41598-020-77757-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710732PMC
December 2020

The association between osteopontin and tuberculosis: A systematic review and meta-analysis.

PLoS One 2020 2;15(12):e0242702. Epub 2020 Dec 2.

Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.

Objective: We examined the data reported in the studies for comparison of osteopontin (OPN) levels in tuberculosis and healthy participants, and to discuss whether OPN could be extended to disease diagnosis, severity assessment and therapeutic effect monitering.

Methods: A systematic literature search was conducted in PubMed, EMBASE, Scopus, the Cochrane Library, Web of Science, the China National Knowledge Infrastructure (CNKI) and WanFang databases. The pooled risk estimates were shown in standardized mean difference (SMD) with 95% confidence interval (CI) for OPN levels. The random effect model was used according to the test of heterogeneity among studies. Subgroup analyses and meta-regression models were performed to identify the possible sources of heterogeneity.

Results: 17 retrospective studies with 933 tuberculosis participants and 786 healthy controls were finally included in this article. In the primary meta-analysis, higher serum/plasma OPN levels were found in tuberculosis patients (SMD = 2.58, 95%CI = 2.09~3.08, P<0.001). Besides, pooled results from positive acid-fast bacilli (AFB) staining and imaging-severe tuberculosis group demonstrated higher OPN concentrations (SMD = 0.90, 95%CI = 0.58~1.21, P<0.001; SMD = 1.11, 95%CI = 0.90~1.33, P<0.001; respectively), and OPN levels decreased after two months of standard anti-tuberculosis therapy (SMD = 2.10, 95%CI = 1.36~2.85, P<0.001).

Conclusions: Elevated serum/plasma OPN levels may be associated with an increased risk of tuberculosis, while further well-designed studies are needed. Moreover, OPN could be considered as a potential biomarker for tuberculosis surveillance and severity assessment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242702PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710079PMC
January 2021

High-Frequency Synchronization Improves Firing Rate Contrast and Information Transmission Efficiency in E/I Neuronal Networks.

Neural Plast 2020 9;2020:8823111. Epub 2020 Nov 9.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Belt and Road Joint Laboratory of Advanced Fiber and Low-Dimension Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.

High-frequency synchronization has been found in many real neural systems and is confirmed by excitatory/inhibitory (E/I) network models. However, the functional role played by it remains elusive. In this paper, it is found that high-frequency synchronization in E/I neuronal networks could improve the firing rate contrast of the whole network, no matter if the network is fully connected or randomly connected, with noise or without noise. It is also found that the global firing rate contrast enhancement can prevent the number of spikes of the neurons measured within the limited time window from being confused by noise, thereby enhancing the information encoding efficiency (quantified by entropy theory here) of the neuronal system. The mechanism of firing rate contrast enhancement is also investigated. Our work implies a possible functional role in information transmission of high-frequency synchronization in neuronal systems.
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http://dx.doi.org/10.1155/2020/8823111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669332PMC
November 2020

Involvement of α7nAChR in the Protective Effects of Genistein Against β-Amyloid-Induced Oxidative Stress in Neurons via a PI3K/Akt/Nrf2 Pathway-Related Mechanism.

Cell Mol Neurobiol 2021 Mar 19;41(2):377-393. Epub 2020 Nov 19.

Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.

Abnormal excessive production and deposition of β-amyloid (Aβ) peptides in selectively susceptible brain regions are thought to be a key pathogenic mechanism underlying Alzheimer's disease (AD), resulting in memory deficits and cognitive impairment. Genistein is a phytoestrogen with great promise for counteracting diverse Aβ-induced insults, including oxidative stress and mitochondrial dysfunction. However, the exact molecular mechanism or mechanisms underlying the neuroprotective effects of genistein against Aβ-induced insults are largely uncharacterized. To further elucidate the possible mechanism(s) underlying these protective effects, we investigated the neuroprotective effects of genistein against Aβ-induced oxidative stress mediated by orchestrating α7 nicotinic acetylcholine receptor (α7nAChR) signaling in rat primary hippocampal neurons. Genistein significantly increased cell viability, reduced the number of apoptotic cells, decreased accumulation of reactive oxygen species (ROS), decreased contents of malondialdehyde (MDA) and lactate dehydrogenase (LDH), upregulated BCL-2 expression, and suppressed Caspase-3 activity occurring after treatment with 25 μM Aβ25-35. Simultaneously, genistein markedly inhibited the decreases in α7nAChR mRNA and protein expression in cells treated with Aβ25-35. In addition, α7nAChR signaling was intimately involved in the genistein-mediated activation of phosphatidylinositol 3-kinase (PI3K)/Akt and Nrf2/keap1 signaling. Thus, α7nAChR activity together with the PI3K/Akt/Nrf2 signaling cascade likely orchestrates the molecular mechanism underlying the neuroprotective effects of genistein against Aβ-induced oxidative injury.
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http://dx.doi.org/10.1007/s10571-020-01009-8DOI Listing
March 2021

Deficits of Tactile Passive Perception Acuity in Patients With Schizophrenia.

Front Psychiatry 2020 27;11:519248. Epub 2020 Oct 27.

Huilongguan College of Clinical Medicine, Peking University, Beijing Huilongguan Hospital, Beijing, China.

Scarce literature has yet to characterize the tactile discrimination capability as well as the underlying mechanism of tactile deficits in psychotic disorder. In particular, very little is known regarding the tactile perception acuity in schizophrenia. A total of 131 clinically stable patients with schizophrenia (SCZ) and 79 healthy control (HC) volunteers were enrolled in the study. All the participants were tested on a tactile stimulus device which could quantify the tactile discrimination capability with right index finger scanned over the angles via the passive finger-movement apparatus. The MATRICS Consensus Cognitive Battery (MCCB) was adapted to assess the neurocognition of the participants. Correlation analysis and multivariate linear regression analysis were performed to investigate the relationship between tactile perception performance and neurocognitive function. It was discovered that there existed a significant deficits in the tactile passive perception acuity (i.e., tactile angle discrimination threshold) in patients with schizophrenia compared with their healthy controls (F = 11.458, = 0.001,partial η = 0.053). The MCCB total score and its six domains were significantly lower in SCZ patients than those in HCs (all < 0.001). In the SCZ group, the composite score of the MCCB ( = -0.312, < 0.001) and domains of neurocognition including speed of processing ( = -0.191, = 0.031), attention/vigilance ( = -0.177, = 0.047), working memory ( = -0.316, < 0.001), verbal learning ( = - 0.332, < 0.001), visual learning ( = -0.260, = 0.004), and reasoning and problem solving ( = -0.209, = 0.018) showed significant negative correlations with the tactile angle discrimination threshold. Multivariate linear regression analysis revealed that neurocognition impairment, especially the decline of working memory (B = -0.312, < 0.001),underpin the tactile perception discrimination deficits in patients with SCZ. To the best of our knowledge, this is the first study to unravel the deficits of tactile passive perception acuity and its underlying neurocognition basis in patients with SCZ. This finding adds novel evidence to the subtle variation in haptic discrimination skills in schizophrenia which contributes to a more comprehensive understanding of the sensory profiles of this disorder.
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http://dx.doi.org/10.3389/fpsyt.2020.519248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652750PMC
October 2020

Hyperoside Attenuates Bleomycin-Induced Pulmonary Fibrosis Development in Mice.

Front Pharmacol 2020 22;11:550955. Epub 2020 Oct 22.

Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China.

Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal, and chronic lung disease. There are no effective drug therapies for IPF. Hyperoside, a flavonoid glycoside, has been proven to have anti-inflammatory, anti-fibrosis, antioxidant, and anti-cancer effects. The aim of this study was to explore the role of hyperoside in bleomycin-induced pulmonary fibrosis development in mice. We established the pulmonary fibrosis model by a single intratracheal aerosol injection of bleomycin. Seven days after the bleomycin treatment, the mice were intraperitoneally administered with hyperoside for 14 days. We found that hyperoside treatment ameliorated fibrotic pathological changes and collagen deposition in the lungs of mice with bleomycin-induced pulmonary fibrosis. Hyperoside treatment also reduced the levels of MDA, TNF-α, and IL-6 and increased the activity of SOD. In addition, hyperoside might inhibit the epithelial-mesenchymal transition (EMT) the AKT/GSK3β pathway. Based on these findings, hyperoside attenuated pulmonary fibrosis development by inhibiting oxidative stress, inflammation, and EMT in the lung tissues of mice with pulmonary fibrosis. Therefore, hyperoside might be a promising candidate drug for the treatment of pulmonary fibrosis.
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http://dx.doi.org/10.3389/fphar.2020.550955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642689PMC
October 2020

[Expression and Clinical Significance of IL-6, IL-10, TNF-α and β-MG in Multiple Myeloma Patients with Different Results of Blood Separation].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Oct;28(5):1625-1630

Department of Laboratory Diagnosis,Cangzhou Hospital of Integrated of Traditional Chinese and Western Medicine of Hebei Province, Cangzhou 061001, Hebei Province, China.

Objective: To investigate the expression level and the clinical significance of serum interleukin-6(IL-6) , IL-10, tumor necrosis factor α(TNF-α) and β-microglobulin(β-MG) in multiple myeloma(MM) patients with different blood separation results.

Methods: The clinical data of 124 newly diagnosed MM patients (76 cases of IgG type, 48 cases of IgA type) treated in our hospital from October 2015 to October 2019 were enrolled and analyzed. The blood samples were divided into control group (the order from top to bottom is serum, separator gel and red blood cells) and abnormal group (the order from top to bottom is serum, red blood cells, separator gel and red blood cells) according to the blood separation result. The differences of expression level in serum IL-6, IL-10, TNF-α and β-MG were compared between the two groups, and the changes of blood separation result and different indexes were analyzed after treatment.

Results: Abnormal separation results were found in 21 cases (16.94%), including 13 cases of IgG type and 8 cases of IgA type. The levels of serum IL-6, IL-10, TNF-α and β-MG in abnormal group were significantly higher than those in control group (P<0.05) . After treatment, 85 patients in control group (103 cases) achieved complete remission (CR) or very good partial remission (VGPR) and partial remission(PR). The results of blood separation showed no change. 18 patients achieved less than PR, and the separation result in 5 patients changed from normal to abnormal separation. The blood separation of 9 patients with CR and VGPR in abnormal group (21 cases) were changed from abnormal to normal. 8 patients achieved PR, and the separation result in 6 patients were changed from abnormal to normal and 2 cases showed no change, while the blood separation showed no changes in 4 cases MM patients who achieved less than PR in abnormal group. The expression levels of IL-6, IL-10, TNF-α and β-MG of patients in control group transformed to abnormal blood separation result after treatment showed significantly higher than those before treatment (P<0.05) , and the levels of IL-6 and β-MG were significantly lower in the patients with out change in blood separation results than those before treatment (P<0.05). The serum levels of IL-6, IL-10, TNF-α and β-MG of patients in abnormal group transformed to normal blood separation after treatment were significantly lower than those before treatment (P<0.05), and the serum levels of IL-6, IL-10, TNF-α and β-MG in abnormal group with no changes in blood separation results showed not significantly different from those before treatment (P>0.05).

Conclusion: Abnormal separation phenomenon can be found after centrifugation in patients with multiple myeloma. The expression levels of serum IL-6, IL-10, TNF-α and β-MG in MM patients with different blood separation results are different, which suggesting different degrees of tumor burden. The changes of blood separation result and levels of IL-6, IL-10, TNF-α and β-MG after treatment can predict the therapeutic effect, and also provide the experimental basis for the evaluation of disease condition and prognosis of patients with different blood separation results.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.05.032DOI Listing
October 2020

Understanding DNA interactions in crowded environments with a coarse-grained model.

Nucleic Acids Res 2020 11;48(19):10726-10738

School of Molecular Sciences and Center for Molecular Design and Biomimetics at the Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.

Nucleic acid interactions under crowded environments are of great importance for biological processes and nanotechnology. However, the kinetics and thermodynamics of nucleic acid interactions in a crowded environment remain poorly understood. We use a coarse-grained model of DNA to study the kinetics and thermodynamics of DNA duplex and hairpin formation in crowded environments. We find that crowders can increase the melting temperature of both an 8-mer DNA duplex and a hairpin with a stem of 6-nt depending on the excluded volume fraction of crowders in solution and the crowder size. The crowding induced stability originates from the entropic effect caused by the crowding particles in the system. Additionally, we study the hybridization kinetics of DNA duplex formation and the formation of hairpin stems, finding that the reaction rate kon is increased by the crowding effect, while koff is changed only moderately. The increase in kon mostly comes from increasing the probability of reaching a transition state with one base pair formed. A DNA strand displacement reaction in a crowded environment is also studied with the model and we find that rate of toehold association is increased, with possible applications to speeding up strand displacement cascades in nucleic acid nanotechnology.
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http://dx.doi.org/10.1093/nar/gkaa854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641764PMC
November 2020