Publications by authors named "Cheng Chen"

1,999 Publications

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Publisher Correction: Environmental eustress modulates β-ARs/CCL2 axis to induce anti-tumor immunity and sensitize immunotherapy against liver cancer in mice.

Nat Commun 2021 Oct 14;12(1):6100. Epub 2021 Oct 14.

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

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http://dx.doi.org/10.1038/s41467-021-26376-8DOI Listing
October 2021

Using soil amendments to reduce microcystin-LR bioaccumulation in lettuce.

Environ Pollut 2021 Oct 11;292(Pt A):118354. Epub 2021 Oct 11.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing, 210008, China.

Contamination of microcystins (MCs) in plant-soil system have become a serious problem worldwide, however, it remains largely unknown how to alleviate the potential risk of consuming MCs-contaminated plants. In the present study, attapulgite, biochar and peat were used as soil amendments to reduce MCs bioaccumulation in lettuce. Lettuce irrigated with 10 μg L microcystin-LR (MC-LR) were growing in two different kinds of soils with or without soil amendments. Results showed that all soil amendments effectively reduced MC-LR bioaccumulation in lettuce roots and leaves. Compared with the control treatment, the MC-LR concentrations in leaves in treatments with attapulgite, biochar and peat decreased by 41.5%, 30.6%, 57.0% in soil A and 38.9%, 43.2%, 54.7% in soil B, respectively. Peat application was most effective in reducing MC-LR bioaccumulation. The decreased soil free MC-LR concentrations were positively correlated with MC-LR concentrations in lettuce, indicating decreased bioavailability of MC-LR by soil amendments. It is noteworthy that soil total MC-LR concentration in peat treatment significantly decreased by 33.3% and 29.4% in soil A and soil B, respectively, compared with the controls. According to the results from high-throughput sequencing, peat amendment increased the α-diversity of soil bacterial community and boosted the abundance of Sphingomonas and Methylobacillus (dozens of MC-degrading bacteria belong to these genera). This was in line with the results of soil total MC-LR concentration. It can be speculated that peat application directly and/or indirectly promoted microbial degradation of MC-LR in soils. This work proposed an effective way to alleviate the potential risks of MCs contamination in plant-soil system.
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http://dx.doi.org/10.1016/j.envpol.2021.118354DOI Listing
October 2021

Direct Visualization and Manipulation of Tunable Quantum Well State in Semiconducting NbSiTe.

ACS Nano 2021 Oct 13. Epub 2021 Oct 13.

School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Quantum well states (QWSs) can form at the surface or interfaces of materials with confinement potential. They have broad applications in electronic and optical devices such as high mobility electron transistor, photodetector, and quantum well laser. The properties of the QWSs are usually the key factors for the performance of the devices. However, direct visualization and manipulation of such states are, in general, challenging. In this work, by using angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy/spectroscopy (STM/STS), we directly probe the QWSs generated on the vacuum interface of a narrow band gap semiconductor NbSiTe. Interestingly, the position and splitting of QWSs could be easily manipulated via potassium (K) dosage onto the sample surface. Our results suggest NbSiTe to be an intriguing semiconductor system to study and engineer the QWSs, which has great potential in device applications.
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http://dx.doi.org/10.1021/acsnano.1c03666DOI Listing
October 2021

Long-term effects of cemented and cementless fixations of total knee arthroplasty: a meta-analysis and systematic review of randomized controlled trials.

J Orthop Surg Res 2021 Oct 12;16(1):590. Epub 2021 Oct 12.

Department of Orthopedics, Nanjing Lishui People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, No. 86 Chongwen Road, Lishui District, Nanjing, 211200, China.

Background: To determine the long-term effects (a minimum follow-up time 8.8 years) of cemented and cementless fixations used for total knee arthroplasty (TKA).

Methods: PubMed, EMBASE, Ovid, Cochrane Library, CINAHL, China National Knowledge Infrastructure and China Wangfang database were interrogated for appropriate randomized controlled trials (RCTs) through July 2020. Data were extracted and assessed for accuracy by 2 of the authors acting independently. Any controversial discrepancies were resolved after discussion with a third author.

Result: Eight RCTs were included with low to moderate bias risks. The cemented fixation of TKA was comparable to cementless fixation in terms of implant survival (relative risk, 1.016; 95% CI 0.978 to 1.056; P = 0.417), Knee Society (KS) knee score (standardized mean difference (SMD), - 0.107; 95% CI - 0.259 to 0.045; P = 0.168), KS function score (SMD - 0.065; 95% CI - 0.238 to 0.109; P = 0.463), KS pain score (SMD - 0.300; 95% CI - 0.641 to 0.042; P = 0.085), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (SMD - 0.117; 95% CI - 0.307 to 0.073; P = 0.227), HSS score (SMD - 0.027; 95% CI - 0.270 to 0.217; P = 0.829), range of motion (SMD 0.061; 95% CI - 0.205 to 0.327; P = 0.652) at ≥ 8.8 years of follow-up. In terms of radiographic outcomes at ≥ 8.8 years of follow-up, the incidence of a radiolucent line in the cementless group was lower than for the cemented group (SMD 3.828; 95% CI 2.228 to 6.576; P < 0.001). However, the maximum total point motion (MTPM) of the cementless group was greater than for the cemented group (SMD - 0.739; 95% CI - 1.474 to - 0.005; P = 0.048).

Conclusions: Long-term follow-up verified that cementless and cemented fixation have similar prosthesis survival rates, clinical scores and mobility. However, radiography suggested that each technique had an advantage with regard to the radiolucent line and MTPM.
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http://dx.doi.org/10.1186/s13018-021-02762-2DOI Listing
October 2021

Reversible transformation between AuAg and AuAg nanoclusters.

Nanoscale 2021 Oct 12. Epub 2021 Oct 12.

Department of Chemistry and Centre for Atomic Engineering of Advanced Materials, Anhui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials, Anhui University, Hefei 230601, P. R. China.

Although several approaches have been exploited to trigger the structural transformation of metal nanoclusters, most cases are assigned to the unidirectional conversion, while the reversible conversion of nanoclusters remains challenging. In this work, the reversible conversion between two Au-Ag alloy nanoclusters, AuAg(Dppm)(CN)Cl and AuAg(Dppm)Cl, has been accomplished, which was tracked by UV-vis and ESI-MS spectroscopy. The condition of the nanocluster reversible conversion has been meticulously mapped out. Our results provide some new insights into the cluster transformation, which will benefit the future preparation of metalloid clusters with customized structures and properties.
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http://dx.doi.org/10.1039/d1nr05123gDOI Listing
October 2021

Learning with Privileged Multimodal Knowledge for Unimodal Segmentation.

IEEE Trans Med Imaging 2021 Oct 11;PP. Epub 2021 Oct 11.

Multimodal learning usually requires a complete set of modalities during inference to maintain performance. Although training data can be well-prepared with high-quality multiple modalities, in many cases of clinical practice, only one modality can be acquired and important clinical evaluations have to be made based on the limited single modality information. In this work, we propose a privileged knowledge learning framework with the 'Teacher-Student' architecture, in which the complete multimodal knowledge that is only available in the training data (called privileged information) is transferred from a multimodal teacher network to a unimodal student network, via both a pixel-level and an image-level distillation scheme. Specifically, for the pixel-level distillation, we introduce a regularized knowledge distillation loss which encourages the student to mimic the teacher's softened outputs in a pixel-wise manner and incorporates a regularization factor to reduce the effect of incorrect predictions from the teacher. For the image-level distillation, we propose a contrastive knowledge distillation loss which encodes image-level structured information to enrich the knowledge encoding in combination with the pixel-level distillation. We extensively evaluate our method on two different multi-class segmentation tasks, i.e., cardiac substructure segmentation and brain tumor segmentation. Experimental results on both tasks demonstrate that our privileged knowledge learning is effective in improving unimodal segmentation and outperforms previous methods.
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http://dx.doi.org/10.1109/TMI.2021.3119385DOI Listing
October 2021

Emulsion-templated porous polymers: drying condition-dependent properties.

Soft Matter 2021 Oct 11. Epub 2021 Oct 11.

College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.

Macroporous materials templated using high internal phase emulsions (HIPEs) are promising for various applications. To date, new strategies to create emulsion-templated porous materials and to tune their properties (especially wetting properties) are still highly required. Here, we report the fabrication of macroporous polymers from oil-in-water HIPEs, bereft of conventional monomers and crosslinking monomers, by simultaneous ring-opening polymerization and interface-catalyzed condensation, without heating or removal of oxygen. The resulting macroporous polymers showed drying condition-dependent wetting properties (, hydrophilicity-oleophilicity from freezing drying, hydrophilicity-oleophobicity from vacuum drying, and amphiphobicity from heat drying), densities (from 0.019 to 0.350 g cc), and compressive properties. Hydrophilic-oleophilic and amphiphobic porous polymers turned hydrophilic-oleophobic simply by heating and protonation, respectively. The hydrophilic-oleophobic porous polymers could remove a small amount of water from oil-water mixtures (including surfactant-stabilized water-in-oil emulsions) by selective absorption and could remove water-soluble dyes from oil-water mixtures. Moreover, the transition in wetting properties enabled the removal of water and dyes in a controlled manner. The feature that combines simply preparation, tunable wetting properties and densities, robust compression, high absorption capacity (rate) and controllable absorption makes the porous polymers to be excellent candidates for the removal of water and water-soluble dyes from oil-water mixtures.
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http://dx.doi.org/10.1039/d1sm00831eDOI Listing
October 2021

Utilizing the Built-in Electric Field of p-n Junctions to Spatially Propel the Stepwise Polysulfide Conversion in Lithium-Sulfur Batteries.

Adv Mater 2021 Oct 10:e2105067. Epub 2021 Oct 10.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.

Integrating sulfur cathodes with effective catalysts to accelerate polysulfide conversion is a suitable way for overcoming the serious shuttling and sluggish conversion of polysulfides in lithium-sulfur batteries. However, because of the sharp differences in the redox reaction kinetics and complicated phase transformation of sulfur, a single-component catalyst cannot consistently accelerate the entire redox process. Herein, hierarchical and defect-rich Co O /TiO p-n junctions (p-Co O /n-TiO -HPs) are fabricated to implement the sequential catalysis of S  → Li S  → Li S . Co O sheets physiochemically immobilize the pristine sulfur and ensure the rapid reduction of S to Li S , while TiO dots realize the effective precipitation of Li S, bridged by the directional migration of polysulfides from p-type Co O to n-type TiO attributed to the interfacial built-in electric field. As a result, the sulfur cathode coupled with p-Co O /n-TiO -HPs delivers long-term cycling stability with a low capacity decay of 0.07% per cycle after 500 cycles at 10 C. This study demonstrates the synergistic effect of the built-in electric field and heterostructures in spatially enhancing the stepwise conversion of polysulfides, which provides novel insights into the interfacial architecture for rationally regulating the polysulfide redox reactions.
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http://dx.doi.org/10.1002/adma.202105067DOI Listing
October 2021

Hepatic dysfunction in patients who received acute DeBakey type I aortic dissection repair surgery: incidence, risk factors, and long-term outcomes.

J Cardiothorac Surg 2021 Oct 10;16(1):296. Epub 2021 Oct 10.

Department of Cardio-Thoracic Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, China.

Background: Hepatic dysfunction (HD) increases the morbidity and mortality rates after cardiac surgery. However, few studies have investigated the association between HD and acute DeBakey type I aortic dissection (ADIAD) surgery. This retrospective study aimed to identify risk factors for developing HD in patients who received acute type I aortic dissection repair and its consequences.

Methods: A total of 830 consecutive patients who received ADIAD surgery from January 2014 to December 2019 at our center were screened for this study. The End-Stage Liver Disease (MELD) score more than 14 was applied to identify postoperative HD. Logistic regression model was applied to identify risk factors for postoperative HD, Kaplan-Meier survival analysis and Cox proportional hazards regression assay were conducted to analyze the association between HD and postoperative long-term survival.

Results: Among 634 patients who eventually enrolled in this study, 401 (63.2%) experienced postoperative HD with a 30-Day mortality of 15.5%. Preoperative plasma fibrinogen level (PFL) [odds ratio (OR): 0.581, 95% confidence interval (CI): 0.362-0.933, P = 0.025], serum creatinine (sCr) on admission (OR: 1.050, 95% CI 1.022-1.079, P < 0.001), cardiopulmonary bypass (CPB) time (OR: 1.017, 95% CI 1.010-1.033, P = 0.039), and postoperative mechanical ventilation (MV) duration (OR: 1.019, 95% CI 1.003-1.035, P = 0.020) were identified as independent risk factors for developing postoperative HD by multivariate analyses. In addition, the Kaplan-Meier analysis indicated that the long-term survival rate was significantly different between patients with or without postoperative HD. However, the hazard ratios of long-term survival for these two groups were not significantly different.

Conclusions: HD was a common complication after ADIAD surgery and associated with an increasing 30-Day mortality rate. Decreased PFL, elevated sCr, prolonged CPB duration, and longer postoperative MV time were independent risk factors for postoperative HD.
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http://dx.doi.org/10.1186/s13019-021-01676-8DOI Listing
October 2021

Combined association of early exposure to long-chain n-3 polyunsaturated fatty acids, mercury and selenium with cognitive performance in 1-year-old infants.

Environ Res 2021 Oct 7:112186. Epub 2021 Oct 7.

Department of Obstetrics and Gynecology, Vagelos College of Physicians and Surgeons, Columbia University, New York, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA. Electronic address:

Background: Previous studies on long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) and infant neurodevelopment did not consider effect modifications of mercury (Hg) and selenium (Se).

Objectives: To examine the joint association of prenatal LCn3PUFAs, Hg and Se with infant cognitive performance, and to explore whether DNA methylation may explain this potential association.

Methods: A total of 484 newborns were enrolled from the Shanghai Birth Cohort with available data on cord blood LCn3PUFA, nail Hg and Se during 2015-2016. Cord blood LCn3PUFA concentrations were assessed by gas chromatography, and nail Hg and Se concentrations were measured using clippings collected within 6 months of birth by inductively coupled plasma mass spectrometry. Five aspects of infant neurodevelopment (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Age and Stage Questionnaire (ASQ) at ages 6 and 12 months. Multivariable-adjusted generalized estimating equations models were performed to examine the associations between cord blood LCn3PUFA concentrations and ASQ test scores, and these associations were stratified by nail Hg and Se levels. Epigenome-wide DNA methylation in cord blood was compared in a random subgroup consisting of 19 infants from the highest and 21 from the lowest decile of LCn3PUFA concentrations.

Results: LCn3PUFAs were not significantly associated with any ASQ test scores. However, in the subgroup with lower Hg (
Conclusion: The association of prenatal LCn3PUFA concentrations with infant neurodevelopment, particularly gross motor skills, may be observed among infants with high Se and low Hg levels.
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http://dx.doi.org/10.1016/j.envres.2021.112186DOI Listing
October 2021

Cell cycle heterogeneity directs spontaneous 2C state entry and exit in mouse embryonic stem cells.

Stem Cell Reports 2021 Sep 24. Epub 2021 Sep 24.

Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China; Zhejiang Laboratory for Systems and Precision Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China; Center of Gene/Cell Engineering and Genome Medicine, Hangzhou, Zhejiang, China. Electronic address:

Mouse embryonic stem cells (ESCs) show cell-to-cell heterogeneity. A small number of two-cell-like cells (2CLCs) marked by endogenous retrovirus activation emerge spontaneously. The 2CLCs are unstable and they are prone to transiting back to the pluripotent state without extrinsic stimulus. To understand how this bidirectional transition takes place, we performed single-cell RNA sequencing on isolated 2CLCs that underwent 2C-like state exit and re-entry, and revealed a step-by-step transitional process between 2C-like and pluripotent states. Mechanistically, we found that cell cycle played an important role in mediating these transitions by regulating assembly of the nucleolus and peri-nucleolar heterochromatin to influence 2C gene Dux expression. Collectively, our findings provide a roadmap of the 2C-like state entry and exit in ESCs and also a causal role of the cell cycle in promoting these transitions.
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http://dx.doi.org/10.1016/j.stemcr.2021.09.003DOI Listing
September 2021

Climate models generally underrepresent the warming by Central Africa biomass-burning aerosols over the Southeast Atlantic.

Sci Adv 2021 Oct 8;7(41):eabg9998. Epub 2021 Oct 8.

Université de Lille, CNRS, UMR 8518, LOA-Laboratoire d'Optique Atmosphérique, 59000 Lille, France.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abg9998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500511PMC
October 2021

Structural and mechanistic insights into the complexes formed by cytoplasmic incompatibility factors.

Proc Natl Acad Sci U S A 2021 Oct;118(41)

School of Life Sciences, Tianjin University, Tianjin, 300072, China;

bacteria, inherited through the female germ line, infect a large fraction of arthropod species. Many strains manipulate host reproduction, most commonly through cytoplasmic incompatibility (CI). CI, a conditional male sterility, results when -infected male insects mate with uninfected females; viability is restored if the female is similarly infected (called "rescue"). CI is used to help control mosquito-borne viruses such as dengue and Zika, but its mechanisms remain unknown. The coexpressed CI factors CifA and CifB form stable complexes in vitro, but the timing and function of this interaction in the insect are unresolved. CifA expression in the female germ line is sufficient for rescue. We report high-resolution structures of a CI-factor complex, CinA-CinB, which utilizes a unique binding mode between the CinA rescue factor and the CinB nuclease; the structures were validated by biochemical and yeast growth analyses. Importantly, transgenic expression in of a nonbinding CinA mutant, designed based on the CinA-CinB structure, suggests CinA expressed in females must bind CinB imported by sperm in order to rescue embryonic viability. Binding between cognate factors is conserved in an enzymatically distinct CI system, CidA-CidB, suggesting universal features in CI induction and rescue.
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http://dx.doi.org/10.1073/pnas.2107699118DOI Listing
October 2021

Chemically Stable Polyarylether-Based Metallophthalocyanine Frameworks with High Carrier Mobilities for Capacitive Energy Storage.

J Am Chem Soc 2021 Oct 7. Epub 2021 Oct 7.

The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.

Covalent organic frameworks (COFs) with efficient charge transport and exceptional chemical stability are emerging as an import class of semiconducting materials for opto-/electronic devices and energy-related applications. However, the limited synthetic chemistry to access such materials and the lack of mechanistic understanding of carrier mobility greatly hinder their practical applications. Herein, we report the synthesis of three chemically stable polyarylether-based metallophthalocyanine COFs (PAE-PcM, M = Cu, Ni, and Co) and facile in situ growth of their thin films on various substrates (i.e., SiO/Si, ITO, quartz) under solvothermal conditions. We show that PAE-PcM COFs thin films with van der Waals layered structures exhibit -type semiconducting properties with the intrinsic mobility up to ∼19.4 cm V s and 4 orders of magnitude of increase in conductivity for PAE-PcCu film (0.2 S m) after iodine doping. Density functional theory calculations reveal that the carrier transport in the framework is anisotropic, with the out-of-plane hole transport along columnar stacked phthalocyanine more favorable. Furthermore, PAE-PcCo shows the redox behavior maximumly contributes ∼88.5% of its capacitance performance, giving rise to a high surface area normalized capacitance of ∼19 μF cm. Overall, this work not only offers fundamental understandings of electronic properties of polyarylether-based 2D COFs but also paves the way for their energy-related applications.
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http://dx.doi.org/10.1021/jacs.1c08265DOI Listing
October 2021

Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes.

Front Mol Biosci 2021 20;8:743013. Epub 2021 Sep 20.

Department of Medical Oncology, Jinling Hospital, Nanjing, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Exosomes, as natural intercellular information carriers, have great potential in the field of drug delivery. Many studies have focused on modifying exosome surface proteins to allow drugs to specifically target cancer cells. In this study, human cord blood mesenchymal stromal cell-derived exosomes were used in the delivery of anti-miRNA oligonucleotides so as to be specifically ingested by tumor cells to perform anti-tumor functions. Mesenchymal stem cells modified by the fusion gene iRGD-Lamp2b were constructed to separate and purify exosomes, and the anti-miRNA-221 oligonucleotide (AMO) was loaded into the exosomes by electroporation. The AMO-loaded exosomes (AMO-Exos) effectively inhibited the proliferation and clonal formation of colon cancer cells , and it was further found that AMO-Exos was taken up by tumor cells through interaction with the NRP-1 protein. The results of a xenograft tumor model also showed that iRGD-modified exosomes were obviously enriched in tumor sites, exerting excellent anti-tumor efficacy. imaging showed that exosomes were mainly distributed in liver, spleen, and lung tissues. Our results suggest that genetically modified exosomes could be an ideal natural nanostructure for anti-miRNA oligonucleotide delivery.
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http://dx.doi.org/10.3389/fmolb.2021.743013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488275PMC
September 2021

Bioinformatics-based identification of SPNS3 (Spinster homolog 3) as a prognostic biomarker of apoptosis resistance in acute myeloid leukemia.

Bioengineered 2021 Dec;12(1):7837-7848

Institute of Blood and Marrow Transplantation, Medical College of Soochow University, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, Soochow University, Suzhou, China.

Spinster homolog 3 (SPNS3) belongs to the Spinster (SPNS) family which participates in sphingolipid transportation through the cell membrane. However, the functions of SPNS3 in acute myeloid leukemia (AML) are unknown. This study obtained SPNS3 from a gene set that was related to AML relapse and evaluate whether high SPNS3 expression induced apoptosis resistance in an AML cell line, which is consistent with the role of SPNS3 as a marker of poor prognosis in the clinic. Moreover, internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) mutation and the AC127521.1/ MIR-139/SPNS3 competing endogenous RNA axis were found to regulate SPNS3 expression. In addition, we noted that SPNS3 may play an important role in the Sphingosine-1-phosphate signal pathway that is involved in the maintenance of the AML microenvironment. These results highlight the anti-apoptosis effect of SPNS3 in AML, and the potential mechanism mediating this effect was explored through bioinformatics. AML: acute myeloid leukemia; FLT3-ITD: internal tandem duplication of FMS-like tyrosine kinase 3; SPNS3: spinster homolog 3; SPNS1: spinster homolog 1; SPNS2: spinster homolog 2; GO: gene ontology; S1P: sphingosine-1-phosphate; ceRNA: competing endogenous RNA; dAML: acute myeloid leukemia at diagnosis; iAML: acute myeloid leukemia after induction chemotherapy; rAML: acute myeloid leukemia at relapse; DEGs: differentially expressed genes; BP: biological processes; CC: cellular components; MF: molecular functions; MRD: minimal residual disease; EFS: event-free survival; OS: overall survival; KEGG: Kyoto Encyclopedia of Genes and Genomes; SPHK: Sphingosine kinase.
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http://dx.doi.org/10.1080/21655979.2021.1982303DOI Listing
December 2021

Hesperetin Exhibits Anti-Inflammatory Effects on Chondrocytes via the AMPK Pathway to Attenuate Anterior Cruciate Ligament Transection-Induced Osteoarthritis.

Front Pharmacol 2021 16;12:735087. Epub 2021 Sep 16.

National Innovation and Attracting Talents "111" Base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.

This study aimed to determine whether hesperetin (HPT) has chondroprotective effects against the TNF-α-induced inflammatory response of chondrocytes and related mechanisms and clarify the impact of HPT on osteoarthritis (OA) induced by anterior cruciate ligament transection (ACLT). Under tumor necrosis factor-α (TNF-α) stimulation, rat chondrocytes were treated with or without HPT. The CCK-8 assay was used to detect viability and cytotoxicity. RT-qPCR and Western blot were used to examine the expression of aggrecan, collagen type II, and inflammatory and proliferative genes/proteins in chondrocytes. Flow cytometry was used to check the cell cycle to determine whether HPT protects chondrocytes against the inhibitory effect of TNF-α on chondrocyte proliferation. In addition, RNA sequencing was used to discover possible molecular targets and pathways and then validate these pathways with specific protein phosphorylation levels. Finally, immunofluorescence staining was used to examine the phosphorylation of the AMP-activated protein kinase (AMPK) pathway. The results showed that HPT restored the upregulation of interleukin 1β (IL-1β), PTGS2, and MMP-13 induced by TNF-α. In addition, HPT reversed the degradation of the extracellular matrix of chondrocytes induced by TNF-α. HPT also reversed the inhibitory effect of TNF-α on chondrocyte proliferation. RNA sequencing revealed 549 differentially expressed genes (DEGs), of which 105 were upregulated and 444 were downregulated, suggesting the potential importance of the AMPK pathway. Progressive analysis showed that HPT mediated the repair of TNF-α-induced chondrocyte damage through the AMPK signaling pathway. Thus, local treatment of HPT can improve OA induced by ACLT. These findings indicated that HPT has significant protective and anti-inflammatory effects on chondrocytes through the AMPK signaling pathway, effectively preventing cartilage degradation. Given the various beneficial effects of HPT, it can be used as a potential natural drug to treat OA.
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http://dx.doi.org/10.3389/fphar.2021.735087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481891PMC
September 2021

Scanning probe microscopy by localized surface plasmon resonance at fiber taper tips.

Rev Sci Instrum 2021 Sep;92(9):093702

State Key Laboratory of Advanced Optical Communication Systems and Networks, Key Laboratory for Thin Film and Microfabrication of the Ministry of Education, Department of Instrument Science & Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Plasmonic antenna probes have been widely investigated for detecting electrical permittivity changes on the nanometer scale by employing high-sensitivity localized surface plasmon resonance (LSPR). Although it is intuitive to integrate such a probe onto an atomic force microscope (AFM) to add one more measurable quantity to the family of scanning probe microscopy techniques, the strong scattering background of the AFM tip overwhelms the LSPR scattering signal. To solve this problem, we combined evanescent coupling, polarization and spatial filtering, confocal spectroscopy, and numerical methods to extract clean LSPR spectra from a gold nanosphere-antenna probe attached to the tip of a fiber taper. By mounting the fiber taper on a custom quartz-tuning-fork SPM, we achieved high-quality nanometer-scale imaging of gold nanospheres on glass slides by mapping the LSPR wavelength shift. In addition, we reported an LSPR wavelength shift enhancement by more complicated probe designs and the consequent promise for higher-sensitivity microscopy. Our optical system and spectral processing method provide an effective solution to the long-standing quest for LSPR scanning microscopy.
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http://dx.doi.org/10.1063/5.0059747DOI Listing
September 2021

Efficacy and Safety of Additional S-1 Chemotherapy to S-1 plus Oxaliplatin Regimen Chemotherapy for Stage III Gastric Carcinoma after Radical Resection.

Cancer Invest 2021 Oct 1:1-11. Epub 2021 Oct 1.

Out-patient Department, First People's Hospital of Huzhou, Huzhou, People's Republic of China.

Objective: To investigate the efficacy and safety of additional S-1 chemotherapy to S-1 plus oxaliplatin (SOX) regimen chemotherapy for Stage III gastric carcinoma (GC) after radical resection.

Patients And Methods: A total of 161 patients who were pathologically diagnosed as Stage III GC after D2 gastrectomy and received SOX regimen adjuvant chemotherapy between January 2012 and April 2016 were included in this retrospective study. SOX regimen postoperative chemotherapy was composed of Oxaliplatin and S-1, administrated every 3 weeks for 8 scheduled courses. After SOX chemotherapy, 76 patients preferred additional chemotherapy with S-1 (the ACT group), while additional S-1 chemotherapy was not given to the other 85 patients (control group). The ACT with S-1 was administrated every 3 weeks for 8 scheduled courses. Treatment was terminated in case of life-threatening adverse events or tumor progression, or patients' demand for termination. Progression-free survival (PFS), overall survival (OS), and adverse events were analysed.

Results: ACT group obtained markedly improved 3-year PFS [P = 0.04; hazard ratio (HR) for disease progression, 0.58; 95% confidence interval (CI), 0.34 to 0.98] and OS than the control group (P = 0.0469; HR for death, 0.56; 95% CI, 0.32 to 0.99). No chemotherapy-related mortality occurred. Patients of the ACT group suffered more common and severer hand-foot syndrome (HFS) (P = 0.02).

Conclusions: Additional S-1 chemotherapy may be helpful for improve the disease progression and survival for patients with Stage III GC after radical resection with an acceptable safety profile.
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http://dx.doi.org/10.1080/07357907.2021.1988961DOI Listing
October 2021

Environmental eustress modulates β-ARs/CCL2 axis to induce anti-tumor immunity and sensitize immunotherapy against liver cancer in mice.

Nat Commun 2021 09 30;12(1):5725. Epub 2021 Sep 30.

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Although psycho-social stress is a well-known factor that contributes to the development of cancer, it remains largely unclear whether and how environmental eustress influences malignant diseases and regulates cancer-related therapeutic responses. Using an established eustress model, we demonstrate that mice living in an enriched environment (EE) are protected from carcinogen-induced liver neoplasia and transplantable syngeneic liver tumors, owning to a CD8 T cell-dependent tumor control. We identify a peripheral Neuro-Endocrine-Immune pathway in eustress, including Sympathetic nervous system (SNS)/β-adrenergic receptors (β-ARs)/CCL2 that relieves tumor immunosuppression and overcomes PD-L1 resistance to immunotherapy. Notably, EE activates peripheral SNS and β-ARs signaling in tumor cells and tumor infiltrated myeloid cells, leading to suppression of CCL2 expression and activation of anti-tumor immunity. Either blockade of CCL2/CCR2 or β-AR signaling in EE mice lose the tumor protection capability. Our study reveales that environmental eustress via EE stimulates anti-tumor immunity, resulting in more efficient tumor control and a better outcome of immunotherapy.
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http://dx.doi.org/10.1038/s41467-021-25967-9DOI Listing
September 2021

Association of Cardiotoxicity With Doxorubicin and Trastuzumab: A Double-Edged Sword in Chemotherapy.

Cureus 2021 Sep 22;13(9):e18194. Epub 2021 Sep 22.

Physiology, The University of Tennessee Health Science Center, Memphis, USA.

Anticancer drugs play an important role in reducing mortality rates and increasing life expectancy in cancer patients. Treatments include monotherapy and/or a combination of radiation therapy, chemotherapy, hormone therapy, or immunotherapy. Despite great advances in drug development, some of these treatments have been shown to induce cardiotoxicity directly affecting heart function and structure, as well as accelerating the development of cardiovascular disease. Such side effects restrict treatment options and can negatively affect disease management. Consequently, when managing cancer patients, it is vital to understand the mechanisms causing cardiotoxicity to better monitor heart function, develop preventative measures against cardiotoxicity, and treat heart failure when it occurs in this patient population. This review discusses the role and mechanism of major chemotherapy agents with principal cardiovascular complications in cancer patients.
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http://dx.doi.org/10.7759/cureus.18194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459919PMC
September 2021

Long non-coding RNA TMCC1-AS1 predicts poor prognosis and accelerates epithelial-mesenchymal transition in liver cancer.

Oncol Lett 2021 Nov 9;22(5):773. Epub 2021 Sep 9.

Department of Nephrology, Affiliated Hospital of Hebei Engineering University, Handan, Hebei 056000, P.R. China.

Long non-coding RNA transmembrane and coiled-coil domain family 1 antisense RNA 1 (TMCC1-AS1) has been frequently reported to be associated with prognosis in patients with liver cancer (LC). However, the biological role of TMCC1-AS1 in LC remains unclear. The expression levels of TMCC1-AS1 in primary tumor tissues and LC cell lines were determined using reverse transcription-quantitative PCR. The associations between TMCC1-AS1 expression and the clinicopathological factors of patients with LC were statistically analyzed using the χ test. The role of TMCC1-AS1 in LC prognosis was assessed using Kaplan-Meier curves and proportional hazards model (Cox) analysis. Cell proliferation was determined by Cell Counting Kit-8 and colony formation assays. Transwell assays were performed to determine migration and invasion. TMCC1-AS1 expression was found to be significantly upregulated in LC tissues and cell lines compared with the corresponding controls. High TMCC1-AS1 expression was associated with advanced TNM stage and lymph node metastasis. Furthermore, high TMCC1-AS1 expression predicted poor survival in patients with LC. Knockdown of TMCC1-AS1 significantly inhibited the proliferation, migration and invasion of HepG2 and SNU-182 cells, while overexpression of TMCC1-AS1 had the opposite effect in HepG2 and SNU-182 cells. At the molecular level, downregulation of TMCC1-AS1 expression resulted in increased E-cadherin expression and decreased proliferating cell nuclear antigen, Ki67, N-cadherin and Vimentin expression in HepG2 cells. Overexpression of TMCC1-AS1 had the opposite effects on these factors in SNU-182 cells. In conclusion, the present findings indicated that TMCC1-AS1 might be considered as a novel oncogene, which promotes cell proliferation and migration, and may be a potential therapeutic target for LC.
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http://dx.doi.org/10.3892/ol.2021.13034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442226PMC
November 2021

Long noncoding RNA Meg3 mediates ferroptosis induced by oxygen and glucose deprivation combined with hyperglycemia in rat brain microvascular endothelial cells, through modulating the p53/GPX4 axis.

Eur J Histochem 2021 Sep 30;65(3). Epub 2021 Sep 30.

Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, Hunan Province.

Individuals with diabetes are exposed to a higher risk of perioperative stroke than non-diabetics mainly due to persistent hyperglycemia. LncRNA Meg3 has been considered as an important mediator in regulating ischemic stroke. However, the functional and regulatory roles of Meg3 in diabetic brain ischemic injury remain unclear. In this study, rat brain microvascular endothelial cells (RBMVECs) were exposed to 6 h of oxygen and glucose deprivation (OGD), and subsequent reperfusion via incubating cells with glucose of various high concentrations for 24 h to imitate in vitro diabetic brain ischemic injury. It was shown that the marker events of ferroptosis and increased Meg3 expression occurred after the injury induced by OGD combined with hyperglycemia. However, all ferroptotic events were reversed with the treatment of Meg3-siRNA. Moreover, in this in vitro model, p53 was also characterized as a downstream target of Meg3. Furthermore, p53 knockdown protected RBMVECs against OGD + hyperglycemic reperfusion-induced ferroptosis, while the overexpression of p53 exerted opposite effects, implying that p53 served as a positive regulator of ferroptosis. Additionally, the overexpression or knockdown of p53 significantly modulated GPX4 expression in RBMVECs exposed to the injury induced by OGD combined with hyperglycemic treatment. Furthermore, GPX4 expression was suppressed again after the reintroduction of p53 into cells silenced by Meg3. Finally, chromatin immunoprecipitation assay uncovered that p53 was bound to GPX4 promoter. Altogether, these data revealed that, by modulating GPX4 transcription and expression, the Meg3-p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic reperfusion.
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http://dx.doi.org/10.4081/ejh.2021.3224DOI Listing
September 2021

Treating Autoimmune Inflammatory Diseases with an siERN1-Nanoprodrug That Mediates Macrophage Polarization and Blocks Toll-like Receptor Signaling.

ACS Nano 2021 Sep 29. Epub 2021 Sep 29.

Department of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing 400016, China.

The clinical application of small interfering RNA (siRNA) drugs provides promising opportunities to develop treatment strategies for autoimmune inflammatory diseases. In this study, siRNAs targeting the endoplasmic reticulum to nucleus signaling 1 () gene (siERN1) were screened. Two cationic polymers, polyethylenimine (PEI) and poly(β-amino amine) (PBAA), which can improve the efficiency of the siRNA transfection, were used as siERN1 delivery carriers. They were implemented to construct a nanodrug delivery system with macrophage-targeting ability and dual responsiveness for the treatment of autoimmune inflammatory diseases. In terms of the mechanism, siERN1 can regulate the intracellular calcium ion concentration by interfering with the function of inositol 1,4,5-trisphosphate receptor 1/3 (IP3R1/3) and thus inducing M2 polarization of macrophages. Furthermore, siERN1-nanoprodrug [FA (folic acid)-PEG-R(RKKRRQRRR)-NPs(ss-PBAA-PEI)@siERN1] acts as a conductor of macrophage polarization by controlling the calcium ion concentration and is an inhibitor of MyD88-dependent Toll-like receptor signaling. The results revealed that the [email protected] has universal biocompatibility, long-term drug release responsiveness, superior targeting properties, and therapeutic effects in mouse collagen-induced arthritis and inflammatory bowel disease models. In conclusion, this study reveals a potential strategy to treat autoimmune inflammatory disorders.
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http://dx.doi.org/10.1021/acsnano.1c03726DOI Listing
September 2021

Integrated analysis reveals distinct molecular, clinical, and immunological features of B7-H3 in acute myeloid leukemia.

Cancer Med 2021 Sep 25. Epub 2021 Sep 25.

Zhenjiang Clinical Research Center of Hematology, Jiangsu, China.

The role of B7-H3 in acute myeloid leukemia (AML) is not fully understood. Two previous studies investigating its expression and significances in AML are partially different. In this study, we aimed to systematically characterize the genomic and immune landscape in AML patients with altered B7-H3 expression using multi-omics data in the public domain. We found significantly increased B7-H3 expression in AML compared to either other hematological malignancies or healthy controls. Clinically, high B7-H3 expression was associated with old age, TP53 mutations, wild-type WT1 and CEBPA, and the M3 and M5 FAB subtypes. Moreover, we observed that increased B7-H3 expression correlated significantly with a poor outcome of AML patients in four independent datasets. Gene set enrichment analysis (GSEA) revealed the enrichment of the "EMT" oncogenic gene signatures in high B7-H3 expressers. Further investigation suggested that B7-H3 was more likely to be associated with immune-suppressive cells (macrophages, neutrophils, dendritic cells, and Th17 cells). B7-H3 was also positively associated with a number of checkpoint genes, such as VISTA (B7-H5), CD80 (B7-1), CD86 (B7-2), and CD70. In summary, we uncovered distinct genomic and immunologic features associated with B7-H3 expression in AML. This may lead to a better understanding of the molecular mechanisms underlying B7-H3 dysregulation in AML and to the development of novel therapeutic strategies.
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http://dx.doi.org/10.1002/cam4.4284DOI Listing
September 2021

Oncologic safety of laparoscopic surgery for women with apparent early-stage uterine serous carcinoma: A multi-institutional retrospective cohort study.

Int J Gynaecol Obstet 2021 Sep 24. Epub 2021 Sep 24.

Department of Obstetrics and Gynecology, Enshi Clinical College of Wuhan University, Enshi, China.

Objective: To compare the long-term survival outcomes of patients with apparent early-stage uterine serous carcinoma (USC) who underwent laparoscopic staging surgery with those who underwent open surgical staging.

Methods: A total of 295 patients from four Chinese teaching hospitals were included. Overall survival (OS) and disease-free survival (DFS) were estimated and compared using the Kaplan-Meier method and the log-rank test among patients after laparoscopic surgery or open surgery. The Cox proportional hazards regression model was applied to adjust for potential confounding factors.

Results: For patients with apparent early-stage USC, laparoscopic surgery was associated with deteriorated DFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.15-2.93, P = 0.012), and there was no significant difference in OS between the two groups (HR 1.74, 95% CI 0.99-3.08, P = 0.056). However, after adjusting for confounding factors, the surgical approach was not an independent prognostic factor for DFS (adjusted HR 1.16, 95% CI 0.63-2.12, P = 0.636) and OS (adjusted HR 1.11, 95% CI 0.52-2.38, P = 0.794) in apparent early-stage USC.

Conclusion: For apparent early-stage USC, laparoscopic surgery is safe. This needs to be confirmed by future prospective clinical trials.
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http://dx.doi.org/10.1002/ijgo.13942DOI Listing
September 2021

What do lifetime hospitalisation patterns tell us about people receiving specialist addiction services in England?

Authors:
Cheng Chen

Lancet Reg Health Eur 2021 Apr 28;3:100045. Epub 2021 Jan 28.

Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA.

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http://dx.doi.org/10.1016/j.lanepe.2021.100045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454799PMC
April 2021

Serum and synovial biomarkers for distinguishing between chronic periprosthetic joint infections and rheumatoid arthritis: a prospective cohort study.

J Arthroplasty 2021 Sep 20. Epub 2021 Sep 20.

Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:

Background: Inflammatory responses in patients with active rheumatoid arthritis (RA) may lead to the current serum and synovial fluid biomarkers that misidentify chronic periprosthetic joint infection (PJI). We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA.

Methods: This prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021, and 30 patients with active RA cumulative knee from August 2020 to March 2021. The Musculoskeletal Infection Society (MSIS) definition of PJI was utilized for the classification of cases as aseptic or infected. Serum D-dimer, ESR, CRP and IL-6, as well as synovial IL-6, PMN% and CD64 index level were measured preoperatively.

Results: An increase in biomarkers concentrations were observed in group C (active RA). Synovial fluid CD64 index exhibited good discriminatory power between group B (chronic PJI) and group C with an area under curve of 0.930. For the diagnosis of chronic PJI in the presence of active RA, the optimal threshold value of synovial CD64 index was 0.87, with a sensitivity of 82.86%, and a specificity of 93.33%.

Conclusions: Current serum biomarkers (ESR, CRP, IL-6 and D-Dimer) did not apply to the diagnosis of suspected PJI with active RA. Fortunately, satisfactory results can be achieved by adjusting the threshold of synovial fluid biomarkers.
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http://dx.doi.org/10.1016/j.arth.2021.09.009DOI Listing
September 2021

Acyclovir inhibits white spot syndrome virus replication in crayfish Procambarus clarkii.

Virus Res 2021 Nov 20;305:198570. Epub 2021 Sep 20.

College of Animal Science and Technology, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi 712100, China. Electronic address:

White spot syndrome virus (WSSV) is a fatal pathogen threatening global crustacean industry with no commercially available drugs to control WSSV. To address the urgent need for finding effective antiviral agents against WSSV, we examined the anti-WSSV activities of 11 common antiviral agents in crayfish Procambarus clarkia. The results showed that acyclovir displayed the highest inhibition on WSSV replication in vivo (92.59%, 50 mg/kg). Acyclovir repressed WSSV proliferation followed a dose-dependent fashion and pre- or post-treatment of acyclovir exerted strong inhibition on the viral loads. Further, we observed a markedly reduced expression levels of WSSV genes (immediate-early IE gene ie1, DNA polymerase gene DNApol and envelope protein gene Vp28) that are crucial in viral life cycle with the acyclovir treatment during the early infection. Meantime, we also found a significantly increased expressions of anti-oxidative as well as apoptosis related genes, suggesting that acyclovir could effectively suppress WSSV replication in vivo. Finally, acyclovir treatment could significantly improve the survival rate of WSSV-challenged crayfish by 56%. Taken together, acyclovir has the potential to be developed as a promising preventive or therapeutic agent against WSSV infection, and this finding may provide a reference for rapid discovery anti-WSSV agent in crustacean aquaculture.
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http://dx.doi.org/10.1016/j.virusres.2021.198570DOI Listing
November 2021

An Intelligent Method for Predicting the Pressure Coefficient Curve of Airfoil-Based Conditional Generative Adversarial Networks.

IEEE Trans Neural Netw Learn Syst 2021 Sep 23;PP. Epub 2021 Sep 23.

Recently, extensive studies have focused on analyzing aerodynamic performance due to its important impact on aircraft design. Most of these works compute the aerodynamic coefficient of the airfoil through computational fluid dynamics (CFD) simulation, which is too time-consuming. To reduce the computational time required, some intelligence-based methods have been presented. However, these methods also suffer from certain issues. First, most of them directly implement existing machine learning methods used to predict the aerodynamic coefficient without adding any improvements. Second, some methods convert the airfoil shape and aerodynamic curves into images, which may lead to curve distortion and the introduction of noise. Third, some methods learn the relationship between the airfoil shape and aerodynamic coefficients but ignore the influence of initial inflow conditions. Accordingly, to address these issues, we propose an intelligent method for predicting the pressure coefficients (Cp) of airfoil based on a conditional generative adversarial network (cGAN). More specifically, we first present a two-step data augmentation strategy designed to expand the original airfoil dataset. Subsequently, we design a novel cGAN-based neural network to predict the Cp curve. To the best of our knowledge, this is the first work to apply generative adversarial network (GAN) to aerodynamic coefficient prediction. Moreover, we design a new loss function to train our network. Extensive experimental results demonstrate that the Cp curve predicted by our method is very close to that generated via CFD simulation. More importantly, our method achieves a speedup close to 1000x compared with CFD simulation.
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http://dx.doi.org/10.1109/TNNLS.2021.3111911DOI Listing
September 2021
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