Publications by authors named "Ning Wu"

603 Publications

A novel electrochemical sensor based on TAPT-TFP-COF/COOH-MWCNT for simultaneous detection of dopamine and paracetamol.

Anal Methods 2021 Oct 11. Epub 2021 Oct 11.

Key Lab of Eco-Environments Related Polymer Materials of MOE, Key Lab of Bioelectrochemistry and Environmental Analysis of Gansu Province, College of Chemistry and Chemical Engineering, Northwest Normal University, Gansu International Scientific and Technological Cooperation Base of Water-Retention Chemical Functional Materials, Lanzhou 730070, PR China.

In this work, a covalent organic framework (COF) TAPT-TFP-COF containing a triazine ring was prepared by a typical Schiff base condensation reaction of 1,3,5-tris-(4-aminophenyl)triazine (TAPT) and 1,3,5-triformyl phloroglucinol (TFP). The TAPT-TFP-COF and carboxyl-functionalized multi-wall carbon nanotubes (COOH-MWCNTs) were drip-coated on glassy carbon electrode respectively to develop a novel and simple electrochemical sensor in order to simultaneously detect dopamine (DA) and paracetamol (PA). COOH-MWCNTs interconnected the TAPT-TFP-COF and acted as bridges between the COF particles, which had a good synergistic effect and accelerated electron transfer. Under optimal conditions, linear responses were obtained over the concentration range 1-190 μM for DA and PA with limits of detection (LOD) of 0.14 μM and 0.19 μM, respectively. Furthermore, the fabricated sensor possesses outstanding repeatability and high selectivity, and can be applied for the determination of DA and PA in dopamine injection and acetaminophen drugs with satisfactory recoveries.
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http://dx.doi.org/10.1039/d1ay01537kDOI Listing
October 2021

Autophagy provides a conceptual therapeutic framework for bone metastasis from prostate cancer.

Cell Death Dis 2021 Oct 5;12(10):909. Epub 2021 Oct 5.

Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 300211, Tianjin, China.

Prostate cancer is a common malignant tumor, which can spread to multiple organs in the body. Metastatic disease is the dominant reason of death for patients with prostate cancer. Prostate cancer usually transfers to bone. Bone metastases are related to pathologic fracture, pain, and reduced survival. There are many known targets for prostate cancer treatment, including androgen receptor (AR) axis, but drug resistance and metastasis eventually develop in advanced disease, suggesting the necessity to better understand the resistance mechanisms and consider multi-target medical treatment. Because of the limitations of approved treatments, further research into other potential targets is necessary. Metastasis is an important marker of cancer development, involving numerous factors, such as AKT, EMT, ECM, tumor angiogenesis, the development of inflammatory tumor microenvironment, and defect in programmed cell death. In tumor metastasis, programmed cell death (autophagy, apoptosis, and necroptosis) plays a key role. Malignant cancer cells have to overcome the different forms of cell death to transfer. The article sums up the recent studies on the mechanism of bone metastasis involving key regulatory factors such as macrophages and AKT and further discusses as to how regulating autophagy is crucial in relieving prostate cancer bone metastasis.
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http://dx.doi.org/10.1038/s41419-021-04181-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492756PMC
October 2021

Low molecular weight fucoidan attenuating pulmonary fibrosis by relieving inflammatory reaction and progression of epithelial-mesenchymal transition.

Carbohydr Polym 2021 Dec 19;273:118567. Epub 2021 Aug 19.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address:

Diffuse alveolar injury and pulmonary fibrosis (PF) are the main causes of death of Covid-19 cases. In this study a low molecular weight fucoidan (LMWF) with unique structural was obtained from Laminaria japonica, and its anti- PF and anti-epithelial-mesenchymal transition (EMT) bioactivity were investigated both in vivo and in vitro. After LWMF treatment the fibrosis and inflammatory factors stimulated by Bleomycin (BLM) were in lung tissue. Immunohistochemical and Western-blot results found the expression of COL2A1, β-catenin, TGF-β, TNF-α and IL-6 were declined in mice lung tissue. Besides, the phosphorylation of PI3K and Akt were inhibited by LMWF. In addition, the progression of EMT induced by TGF-β1 was inhibited by LMWF through down-regulated both TGF-β/Smad and PI3K/AKT signaling pathways. These data indicate that unique LMWF can protect the lung from fibrosis by weakening the process of inflammation and EMT, and it is a promising therapeutic option for the treatment of PF.
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http://dx.doi.org/10.1016/j.carbpol.2021.118567DOI Listing
December 2021

Involvement of the nociceptin opioid peptide receptor in morphine-induced antinociception, tolerance and physical dependence in female mice.

Metab Brain Dis 2021 Sep 16. Epub 2021 Sep 16.

Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing, 100850, China.

Nociceptin opioid peptide (NOP) receptor modulates pain transmission and is considered a prospective target for pain management. Under acute pain conditions in rodents, however, no definitive conclusions about effects of systemically intervening NOP receptors on nociception, classical opioid-induced antinociception, tolerance and physical dependence have been drawn. Given that opioid analgesia has sex differences, and females experience greater pain and consume more opioids, clarifying these issues in females will help develop novel analgesics. To clarify the role of NOP receptors on the pharmacological profiles of µ-opioid receptor agonists, in this study, a selective agonist (SCH221510) and antagonist (SB612111) of the NOP receptor were subcutaneously administered in female mice in multiple animal models. In hot-plate test, neither SCH221510 (3 and 10 mg/kg, sc) nor SB612111 (10 mg/kg, sc) produced significant antinociception. SCH221510 (3 mg/kg, sc) attenuated but SB612111 (10 mg/kg, sc) enhanced morphine-induced antinociception, with rightward and leftward shift of morphine dose-response curves, respectively. SCH221510 (3 mg/kg, sc) combined with morphine (10 mg/kg, sc) accelerated the development of morphine antinociceptive tolerance. Conversely, SB612111 (10 mg/kg, sc) delayed morphine tolerance development. Neither SCH221510 (3 mg/kg, sc) nor SB612111 (10 mg/kg, sc) statistically significantly altered the development of morphine-induced physical dependence. Therefore, systemic activation of NOP receptors attenuated morphine antinociception to acute thermal stimuli, facilitated morphine-induced antinociceptive tolerance but did not robustly alter physical dependence in female mice. Systemic blockade of NOP receptors produced opposite actions. These findings demonstrate that N/OFQ-NOP receptor system plays diverse roles in modulating pharmacological profiles of µ-opioid receptor agonists.
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http://dx.doi.org/10.1007/s11011-021-00783-8DOI Listing
September 2021

Effect of Root Canal Therapy Combined with Full Crown Restoration on the Level of Inflammatory Factors and Chewing Function in Patients with Cracked Teeth and Chronic Pulpitis.

Evid Based Complement Alternat Med 2021 30;2021:3299349. Epub 2021 Aug 30.

Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Huangpu, Shanghai 200011, China.

Objective: To explore the clinical effect of root canal therapy combined with full crown restoration in patients with cracked teeth and chronic pulpitis.

Methods: From May 2018 to June 2020, 87 patients with cracked teeth and chronic pulpitis in our hospital were selected; the patients were randomly divided into the control group and the research group by random number method. The control group only used root canal therapy; the research group used root canal therapy combined with full crown restoration. The therapeutic effect, levels of inflammatory factors, chewing function, periodontal index, complications, and quality of life were compared between the two groups.

Results: The total effective rate of the research group (97.78%) was better than the total effective rate of the control group (85.71%) ( < 0.05). Compared with before treatment, the serum levels of interleukin-1 (IL-1), IL-6, and C-reactive protein (CRP) of the two groups of patients decreased after treatment. After treatment, compared with the control group, the serum levels of IL-1, IL-6, and CRP in the research group decreased ( < 0.05). Compared with before treatment, the bite force of teeth and chewing efficiency of the two groups of patients increased after treatment. After treatment, compared with the control group, the bite force of teeth and chewing efficiency of the research group increased ( < 0.05). Compared with before treatment, the plaque index (PLI), probing depth (PD), gingival sulcus bleeding index (BI), and gingival index (GI) of the two groups of patients decreased after treatment. After treatment, compared with the control group, the PLI, PD, BI, and GI of the research group decreased ( < 0.05). The total incidence of complications in the research group was (11.11%), and the total incidence of complications in the control group was (16.67%); there was no significant difference between the two groups ( > 0.05). After treatment, compared with the control group, the quality of life scores of the patients in the research group were reduced ( < 0.05).

Conclusion: Root canal therapy and full crown restoration have a definite curative effect in patients with cracked teeth and chronic pulpitis, which can improve the inflammatory response, restore chewing function, maintain periodontal health, improve the quality of life, and do not increase the incidence of complications, so it has good application value.
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http://dx.doi.org/10.1155/2021/3299349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423566PMC
August 2021

Synthesis, Crystal Structure and Bioactivity of Phenazine-1-carboxylic Acylhydrazone Derivatives.

Molecules 2021 Sep 1;26(17). Epub 2021 Sep 1.

Department of Chemistry, University of Hull, Cottingham Road, Hull HU6 7RX, UK.

A phenazine-1-carboxylic acid intermediate was synthesized from the reaction of aniline and 2-bromo-3-nitro-benzoic acid. It was then esterified and reacted with hydrazine hydrate to afford phenazine-1-carboxylic hydrazine. Finally, 10 new hydrazone compounds - were obtained by the condensation reaction of phenazine-1-carboxylic acid hydrazide and the respective aldehyde-containing compound. The structures were characterized by H and C NMR spectroscopy, MS and single crystal X-ray diffraction. The antitumor activity of the target compounds in vitro (HeLa and A549) was determined by thiazolyl blue tetrazolium bromide. The results showed that compound ()-'-(2-hydroxy-4-(2-(piperidine-1-yl) ethoxy) benzyl) phenazine-1-carbonyl hydrazide exhibited good cytotoxic activity.
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http://dx.doi.org/10.3390/molecules26175320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434039PMC
September 2021

TXNIP interaction with GLUT1 depends on PI(4,5)P.

Biochim Biophys Acta Biomembr 2021 Dec 31;1863(12):183757. Epub 2021 Aug 31.

Van Andel Institute, Grand Rapids, MI 49503, USA. Electronic address:

GLUT1 is a major glucose facilitator expressed ubiquitously among tissues. Upregulation of its expression plays an important role in the development of many types of cancer and metabolic diseases. Thioredoxin-interacting protein (TXNIP) is an α-arrestin that acts as an adaptor for GLUT1 in clathrin-mediated endocytosis. It regulates cellular glucose uptake in response to both intracellular and extracellular signals via its control on GLUT1-4. In order to understand the interaction between GLUT1 and TXNIP, we generated GLUT1 lipid nanodiscs and carried out isothermal titration calorimetry and single-particle electron microscopy experiments. We found that GLUT1 lipid nanodiscs and TXNIP interact in a 1:1 ratio and that this interaction requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P or PIP).
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http://dx.doi.org/10.1016/j.bbamem.2021.183757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464517PMC
December 2021

Priority of PET-CT vs CT Thorax for EBUS-TBNA 22G vs 19G: Mesothorax Lymphadenopathy.

J Cancer 2021 5;12(19):5874-5878. Epub 2021 Aug 5.

Ear, Nose and Throat (ENT) Department, Ludwig-Maximilians University of Munich, Munich, Germany.

Lung lesions and undiagnosed mesothorax lymphadenopathy is an issue that several doctors face in the everyday clinical practice. PET-CT and CT of the thorax are usually the first examinations to identify characteristics of the lesions before biopsy. We performed a retrospective study with 450 patients that had EBUS-TBNA with 22G, Upgraded 22G and 19G needles with and without PET-CT in order to identify the cost effeteness of performing EBUS-TBNA before or after PET-CT. All centers used the same PET-CT equipment and EBUS-TBNA system. Three types of needle were used for the endoscopy in order to identify similarities and differences for the cost-effectiveness. The costs in every center for every examination and materials were the same. There were more block slices for 19G>22Gupgraded>21G>22G and there was cost-effectiveness when in general PET-CT was performed prior to biopsy of any lesion. 19G needle was more effective for lymphomas, while 22Gupgraded and 21G needles were more cost-effective when used for smaller lesions for primary lung cancer of metastatic disease. We have been using PET-CT and EBUS-TBNA in the everyday clinical practice according to the current guidelines for initial disease staging and re-staging. However; we can also use both in a cost effective method based on the initial radiologic findings.
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http://dx.doi.org/10.7150/jca.59892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408124PMC
August 2021

Comparison of Radiation Dose and Image Quality Between Split-Filter Twin Beam Dual-Energy Images and Single-Energy Images in Single-Source Contrast-Enhanced Chest Computed Tomography.

J Comput Assist Tomogr 2021 Aug 31. Epub 2021 Aug 31.

From the Department of Diagnostic Radiology PET-CT Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: To compare image quality and radiation dose of split-filter TwinBeam dual-energy (SF-TBDE) with those of single-energy images (SECT) in the contrast-enhanced chest computed tomography (CT).

Methods: Two hundred patients who underwent SF-TBDE (n = 100) and SECT (n = 100) contrast-enhanced chest scanning were retrospectively analyzed. The contrast-to-noise ratio (CNR) and figure of merit (FOM)-CNR of 5 structures (lung, aorta, pulmonary artery, thyroid, and erector spinae) were calculated and subjectively evaluated by 2 independent radiologists. Radiation dose was compared using volume CT dose index and size-specific dose estimate.

Results: The CNR and FOM-CNR of lung and erector spinae in SF-TBDE were higher than those of SECT (P < 0.001). The differences in the subjective image quality between the 2 groups were not significant (P = 0.244). Volume CT dose index and size-specific dose estimate of SF-TBDE were lower than those of SECT (6.60 ± 1.56 vs 7.81 ± 3.02 mGy, P = 0.001; 9.25 ± 1.60 vs. 10.55 ± 3.54; P = 0.001).

Conclusions: The SF-TBDE CT can provide similar image quality at a lower radiation dose compared with SECT.
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http://dx.doi.org/10.1097/RCT.0000000000001220DOI Listing
August 2021

Purification, characterization and immunostimulatory activity of a novel exopolysaccharide from Bacillus sp. H5.

Int J Biol Macromol 2021 Oct 25;189:649-656. Epub 2021 Aug 25.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address:

Crude exopolysaccharides from extracellular polymeric substances produced by the marine bacterium Bacillus sp. H5 were fractionated using DEAE-Sepharose FF and Sephadex G-75 chromatography. The high molecular weight fraction (89.0 kD) from the neutral fraction was designated EPS5SH; it contained mannose, glucosamine, glucose, and galactose in a molar ratio of 1.00: 0.02: 0.07: 0.02. Infra-red, gas chromatography-mass spectrometry, electrospray ionisation-tandem mass spectrometry analysis and nuclear magnetic resonance revealed EPS5SH was a mannan with α-(1 → 4)-Manp, α-(1 → 2)-Manp, α-(1 → 4, 6)-Manp and β-terminal-Manp. Preliminary in vitro experiments revealed that EPS5SH significantly upregulated nitric oxide synthesis and release of pro-inflammatory factors in murine macrophage RAW264.7 cells. Western blot experiments verified the immunostimulatory effects of EPS5SH through the modulation of the NF-κB and MAPK signalling pathways. In conclusion, EPS5SH was a novel immunostimulatory mannan.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.159DOI Listing
October 2021

Formulation Comprising Arsenic Trioxide and Dimercaprol Enhances Radiosensitivity of Pancreatic Cancer Xenografts.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211036324

Department of Traditional Chinese Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: To investigate the efficacy of a formula comprising arsenic trioxide and dimercaprol (BAL-ATO) as a radiosensitizing agent in model mice with pancreatic cancer xenografts.

Methods: Female BALB/c nude mice bearing SW1990 human pancreatic cancer xenografts were divided into four treatment arms, including control, radiotherapy (RT), BAL-ATO, and RT + BAL-ATO groups. Survival and tumor volume were analyzed. We also assessed apoptosis in tumor samples by live imaging and detected hypoxia by confocal laser microscope observation. We further investigated the mechanisms of BAL-ATO action in RT by detecting affected proteins by western blot and immunohistochemistry assays.

Results: Median survival was significantly longer in the RT + BAL-ATO group (64.5 days) compared with the control (49.5 days), RT (39 days), and BAL-ATO (48 days) groups ( 0.001). RT + BAL-ATO inhibited the growth of tumors in mice by 73% compared with the control group, which was significantly higher than the rate of inhibition following RT alone (59%) ( < 0.01). Further analysis showed an improved microenvironment in terms of hypoxia in tumors treated with BAL-ATO alone or RT + BAL-ATO. Expression of signaling molecules associated with pancreatic cancer stem cells, including CD24, CD44, ALDH1A1, Gli-1, and Nestin, was detected in tumors treated with BAL-ATO alone or in combination with RT.

Conclusion: These data suggest that BAL-ATO function as a radiosensitizer in mice with pancreatic cancer xenografts, via mechanisms involving hypoxia reduction and inhibition of signaling pathways associated with pancreatic cancer stem cells. BAL-ATO may thus be a promising radiosensitizing agent in patients with pancreatic cancer.
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http://dx.doi.org/10.1177/15330338211036324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404670PMC
August 2021

Diagnosis of retrotracheal left brachiocephalic vein with prenatal ultrasound: a case report.

Transl Pediatr 2021 Jul;10(7):1960-1964

Department of Ultrasound, Ningxia Hui Autonomous Region Maternity and Child Health Hospital & Ningxia Children's Hospital, Yinchuan, China.

Retroesophageal or retrotracheal left brachiocephalic vein (LBCV) is a rare anatomic variant that is often associated with congenital heart disease. It is rarely reported in fetal life, and an isolated fetal retroesophageal LBCV has a good prognosis: it is typically asymptomatic, although respiratory symptoms or swallowing disorders occasionally occur. A variant was observed on fetal echocardiography at 22 weeks of gestation. The 3-vessel view revealed a transverse section of a vessel to the left of the pulmonary artery. Tracing upwards along its long axis showed that the left subclavian vein joined the left internal jugular vein to form the LBCV, and tracing downwards revealed that the vessel traveled to the right and lower side, where it merged into the superior vena cava via the azygos vein behind the aortic arch. The variant was identified as retrotracheal LBCV. Three-dimensional (3D) reconstruction of fetal great vessels was performed using temporal spatial correlation imaging. The left internal jugular vein and the left subclavian vein converged into the LBCV, then bypassed behind the trachea and converged into the superior vena cava via the azygous vein. As a 3D technique, spatio-temporal image correlation (STIC) can visualize the abnormal courses of LBCV, thus improving the diagnostic accuracy. This article presents the 2-dimensional (2D) ultrasound, color Doppler, and STIC findings of an isolated retrotracheal LBCV, which may inform the sonographic diagnosis of such variants.
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http://dx.doi.org/10.21037/tp-21-230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349951PMC
July 2021

Retraction Note: Overexpression of miR-499-5p inhibits non-small cell lung cancer proliferation and metastasis by targeting VAV3.

Sci Rep 2021 08 23;11(1):17295. Epub 2021 Aug 23.

Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University, Shanghai, 200072, China.

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http://dx.doi.org/10.1038/s41598-021-96814-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496552PMC
August 2021

Different Clinicopathologic and Computed Tomography Imaging Characteristics of Primary and Acquired Mutations in Patients with Non-Small-Cell Lung Cancer.

Cancer Manag Res 2021 13;13:6389-6401. Epub 2021 Aug 13.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Purpose: Although patients with primary and acquired epidermal growth factor receptor (EGFR) positive non-small-cell lung cancer (NSCLC) respond to osimertinib treatment, the optimal treatment strategy differs for these two groups of patients. This study aimed to compare the clinicopathologic and computed tomography (CT) imaging characteristics between primary and acquired mutations in patients with NSCLC before treatment.

Patients And Methods: We enrolled two groups of patients with primary or acquired mutation NSCLC (n = 103 per group) from January 2012 to December 2019. We analyzed their clinicopathologic and CT characteristics and differences between the groups. The groups were further categorized based on and to exclude the effect of coexistent mutations.

Results: Primary, compared to acquired, mutation tends to coexist with (P < 0.001), exhibiting earlier tumor stage (P < 0.001), higher differentiation (P = 0.029), higher proportion of lepidic subtype adenocarcinoma (P < 0.001), and significant associations with some CT features (multiple primary lung cancers, ground-glass opacity, air bronchogram, and vacuole sign [all P < 0.001]). The combined model, composed of clinicopathologic and conventional CT signature and CT-radiomic signature, showed good discriminative ability with the area under the receiver operating characteristic curve 0.90 and 0.91 in the training and validation datasets, respectively. The mutation contributed to these differences independently of coexistent mutations.

Conclusion: We identified clinicopathologic and CT imaging differences between primary and acquired mutations. These findings provide insights into developing future personalized mutation status-based theranostic strategies.
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http://dx.doi.org/10.2147/CMAR.S323972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370596PMC
August 2021

Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.

Nat Immunol 2021 09 19;22(9):1127-1139. Epub 2021 Aug 19.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Follicular helper T (T) cells are a specialized subset of CD4 T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of T cell survival remains unclear. Here we report that T cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for T cell survival. The deletion of GPX4 in T cells selectively abrogated T cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased T cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating T homeostasis, which can be targeted to enhance T cell function in infection and following vaccination.
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http://dx.doi.org/10.1038/s41590-021-00996-0DOI Listing
September 2021

A Network Approach to the Study of the Dynamics of Risk Spillover in China's Bond Market.

Entropy (Basel) 2021 Jul 20;23(7). Epub 2021 Jul 20.

School of Economics and Management, University of Chinese Academy of Sciences, Beijing 100190, China.

Since 2018, the bond market has surpassed the stock market, becoming the biggest investment area in China's security market, and the systemic risks of China's bond market are of non-negligible importance. Based on daily interest rate data of representative bond categories, this study conducted a dynamic analysis based on generalized vector autoregressive volatility spillover variance decomposition, constructed a complex network, and adopted the minimum spanning tree method to clarify and analyze the risk propagation path between different bond types. It is found that the importance of each bond type is positively correlated with liquidity, transaction volume, and credit rating, and the inter-bank market is the most important market in the entire bond market, while interest rate bonds, bank bonds and urban investment bonds are important varieties with great systemic importance. In addition, the long-term trend of the dynamic spillover index of China's bond market falls in line with the pace of the interest rate adjustments. To hold the bottom line of preventing financial systemic risks of China's bond market, standard management, strict supervision, and timely regulation of the bond markets are required, and the structural entropy, as a useful indicator, also should be used in the risk management and monitoring.
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http://dx.doi.org/10.3390/e23070920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303115PMC
July 2021

Excess dietary carbohydrate affects mitochondrial integrity as observed in brown adipose tissue.

Cell Rep 2021 Aug;36(5):109488

Van Andel Institute, Grand Rapids, MI 49503, USA. Electronic address:

Hyperglycemia affects over 400 million individuals worldwide. The detrimental health effects are well studied at the tissue level, but the in vivo effects at the organelle level are poorly understood. To establish such an in vivo model, we used mice lacking TXNIP, a negative regulator of glucose uptake. Examining mitochondrial function in brown adipose tissue, we find that TXNIP KO mice have a lower content of polyunsaturated fatty acids (PUFAs) in their membrane lipids, which affects mitochondrial integrity and electron transport chain efficiency and ultimately results in lower mitochondrial heat output. This phenotype can be rescued by a ketogenic diet, confirming the usefulness of this model and highlighting one facet of early cellular damage caused by excess glucose influx.
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http://dx.doi.org/10.1016/j.celrep.2021.109488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449951PMC
August 2021

γδ T Cells May Aggravate Acute Graft-Versus-Host Disease Through CXCR4 Signaling After Allogeneic Hematopoietic Transplantation.

Front Immunol 2021 14;12:687961. Epub 2021 Jul 14.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

Graft-versus-host disease (GVHD) is a pathology in which chemokines and their receptors play essential roles in directing the migration of alloreactive donor T cells into GVHD organs, thereby leading to further target tissue damage. Currently, acute GVHD (aGVHD) remains a major cause of high morbidity and mortality in patients who underwent allogeneic hematopoietic cell transplantation (alloHCT). The identification of immune cells that correlate with aGVHD is important and intriguing. To date, the involvement of innate-like γδ T cells in the pathogenesis of aGVHD is unclear. Herein, we found that primary human γδ T cells did not directly trigger allogeneic reactions. Instead, we revealed that γδ T cells facilitated the migration of CD4 T cells the SDF-1-CXCR4 axis. These results indicate indirect regulation of γδ T cells in the development of aGVHD rather than a direct mechanism. Furthermore, we showed that the expression of CXCR4 was significantly elevated in γδ T cells and CD4 and CD8 T cells in recipients who experienced grades II-IV aGVHD after alloHCT. Consistently, CXCR4-expressing γδ T cells and CD4 T cells were induced in the target organs of mice suffering aGVHD. The depletion of γδ T cells in transplant grafts and treatment with AMD3100, an inhibitor of CXCR4 signaling, delayed the onset of aGVHD and prolonged survival in mice. Taken together, these findings suggest a role for γδ T cells in recruiting alloreactive CD4 T cells to target tissues through the expression of CXCR4. Our findings may help in understanding the mechanism of aGVHD and provide novel therapeutic targets.
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http://dx.doi.org/10.3389/fimmu.2021.687961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316995PMC
July 2021

Synthesis and Propulsion of Magnetic Dimers under Orthogonally Applied Electric and Magnetic Fields.

Langmuir 2021 Aug 22;37(30):9151-9161. Epub 2021 Jul 22.

Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, Colorado 80401, United States.

Anisotropic particles have been widely used to make micro/nanomotors that convert chemical, ultrasonic, electrical, or magnetic energy into mechanical energy. The moving directions of most colloidal motors are, however, difficult to control. For example, asymmetric dimers with two lobes of different sizes, ζ-potential, or chemical composition have shown rich propulsion behaviors under alternating current (AC) electric fields due to unbalanced electrohydrodynamic flow. While they always propel in a direction perpendicular to the applied electric field, their moving directions along the substrate are hard to control, limiting their applications for cargo delivery. Inspired by two separate engine and steering wheel systems in automobiles, we use orthogonally applied AC electric field and direct current (DC) magnetic field to control the dimer's speed and direction independently. To this end, we first synthesize magnetic dimers by coating dopamine-functionalized nanoparticles on geometrically asymmetric polystyrene dimers. We further characterize their static and dynamic susceptibilities by measuring the hysteresis diagram and rotation speed experimentally and comparing them with theoretical predictions. The synthesized dimers align their long axes quickly with a planar DC magnetic field, allowing us to control the particles' orientation accurately. The propulsion speed of the dimers, on the other hand, is tunable by an AC electric field applied perpendicularly to the substrate. As a result, we can direct the particle's motion with predesigned trajectories of complex shapes. Our bulk-synthesis approach has the potential to make other types of magnetically anisotropic particles. And the combination of electric and magnetic fields will help pave the way for the assembly of magnetically anisotropic particles into complex structures.
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http://dx.doi.org/10.1021/acs.langmuir.1c01329DOI Listing
August 2021

Association of anaplastic lymphoma kinase variants and alterations with ensartinib response duration in non-small cell lung cancer.

Thorac Cancer 2021 Sep 20;12(17):2388-2399. Epub 2021 Jul 20.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression-free survival (PFS).

Methods: We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. We also established a multifactorial model of clinicopathological and quantitative CT radiomic features to predict PFS and risk stratification. Kaplan-Meier analysis was conducted to identify risk factors for tumor progression.

Results: Univariate analysis indicated a statistical difference (p = 0.035) in PFS among ALK variants in three classifications (V1, V3, and other variants). Secondary ALK alterations were adversely associated with PFS both in univariate (p = 0.008) and multivariate (p = 0.04) analyses and could identify patients at high risk for early progression in the Kaplan-Meier analysis (p = 0.002). Additionally, response duration to crizotinib <1 year and liver metastasis were adversely associated with PFS. The combined model, composed of clinicopathological signature and CT radiomic signature, showed good prediction ability with the area under the receiver operating characteristic curve being 0.85, and 0.89 in the training and validation dataset respectively.

Conclusions: Our study showed that secondary ALK alterations were adversely associated with ensartinib efficacy, and that ALK variants might not correlate with PFS. The quantitative radiomic signature provided added prognostic prediction value to the clinicopathological features.
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http://dx.doi.org/10.1111/1759-7714.14083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410530PMC
September 2021

Synthesis of molecularly imprinted microspheres and development of a fluorescence method for detection of chloramphenicol in meat.

Luminescence 2021 Nov 3;36(7):1767-1774. Epub 2021 Aug 3.

Henan Institute of Veterinary Drug and Feed Control, Zhengzhou, Henan, China.

In this study, nitrobenzene was used as dummy template to synthesize a type of specific molecularly imprinted microspheres for chloramphenicol, and 4-nitroaniline was coupled with three fluorophores to synthesize three fluorescent tracers. Then a competitive fluorescence method was developed on a conventional microplate for detection of chloramphenicol in chicken and pork samples. This method contained only one sample-loading step, so one assay was finished within 30 min. The IC was 1.8 ng/ml, and the limit of detection was 0.06 ng/g. The recoveries from chloramphenicol-fortified blank meat samples were in the range 67.5-96.2%. Furthermore, this method could be recycled three times. The detection results for some real meat samples were identical to that of a LC-MS/MS method. Therefore, this method could be used as a practical tool for routine screening for the residue of chloramphenicol in large number of meat samples.
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http://dx.doi.org/10.1002/bio.4121DOI Listing
November 2021

Network Pharmacology Analysis of the Mechanisms of Compound Herba Sarcandrae (Fufang Zhongjiefeng) Aerosol in Chronic Pharyngitis Treatment.

Drug Des Devel Ther 2021 28;15:2783-2803. Epub 2021 Jun 28.

Department of Mathematics and Statistics, University of Calgary, Calgary, Alberta, Canada.

Purpose: This study aimed to investigate the molecular mechanisms of compound herba Sarcandrae aerosol, also known as the Fufang Zhongjiefeng (FFZJF) aerosol, in treating chronic pharyngitis (CP) using network pharmacology and in vivo experimental approaches.

Methods: Active compounds and putative targets of five herbs in FFZJF were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction databases. The therapeutic targets of CP were obtained from OMIM, Durgbank, DisGeNT, and GAD databases. The active compounds-target networks were constructed using Cytoscape 3.6.1. The overlapping targets of FFZJF active compounds and CP targets were further analyzed using the String database to construct protein-protein interaction (PPI) network. KEGG pathway and Gene Ontology enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery. The predicted targets and pathways were validated in a group A β-hemolytic streptococcus-induced rat CP model.

Results: There were 45 active compounds identified from FFZJF and 11 potential protein targets identified for CP treatment. PPI network demonstrated that IL6, PTGS2, TLR-4, and TNF may serve as the key targets of FFZJF for the treatment of CP. The main functional pathways involving these key targets include cytokine secretion, inflammatory response, MyD88-dependent toll-like receptor signaling pathway, toll-like receptor signaling pathway, TNF signaling pathway, and NF-κB signaling pathway. In a rat CP model, the elevation of serum TNF-α, IL1β, and IL6 levels, as well as the upregulation of TLR-4, MyD88, NF-κB P65 in the pharyngeal mucosal tissues could be effectively reduced by FFZJF treatment in a dose-dependent manner.

Conclusion: Through a network pharmacology approach and animal study, we predicted and validated the active compounds of FFZJF and their potential targets for CP treatment. The results suggest that FFZJF can markedly alleviate GAS-induced chronic pharyngitis by modulating the TLR-4/MyD88/NF-κB signaling pathways.
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http://dx.doi.org/10.2147/DDDT.S304708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254411PMC
June 2021

Determining cost-effectiveness of lung cancer screening in urban Chinese populations using a state-transition Markov model.

BMJ Open 2021 07 1;11(7):e046742. Epub 2021 Jul 1.

Department of Health Economics, College of Health Management, Harbin Medical University, Harbin, China

Objectives: This study analyses the cost-effectiveness of annual low-dose CT (LDCT) screening of high-risk cancer populations in Chinese urban areas.

Design: We used a Markov model to evaluate LDCT screening from a sociological perspective.

Setting: The data from two large lung cancer screening programmes in China were used.

Participants: The sample consisted of 100 000 smokers who underwent annual LDCT screening until age 76.

Intervention: The study comprises five screening strategies, with the initial screening ages in both the screening strategies and their corresponding non-screening strategies being 40, 45, 50, 55 and 60 years, respectively.

Primary And Secondary Outcome Measures: The incremental cost-effectiveness ratio (ICER) between screening and non-screening strategies at the same initial age was evaluated.

Results: In the baseline scenario, compared with those who were not screened, the specific mortality from lung cancer decreased by 18.52%-23.13% among those who underwent screening. The ICER of LDCT screening ranges from US$13 056.82 to US$15 736.06 per quality-adjusted life year, which is greater than one but less than three times the gross domestic product per capita in China. An initial screening age of 55 years is the most cost-effective strategy.

Conclusions: Baseline analysis shows that annual LDCT screening of heavy smokers in Chinese urban areas is likely to be cost-effective. The sensitivity analysis reveals that sensitivity, specificity and the overdiagnosis rate influence the cost-effectiveness of LDCT screening. All scenarios tested demonstrate cost-effectiveness, except for the combination of worst values of sensitivity, specificity and overdiagnosis. Therefore, the cost-effectiveness of a screening strategy depends on the performance of LDCT screenings.
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http://dx.doi.org/10.1136/bmjopen-2020-046742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252866PMC
July 2021

Metabolic profiling analysis for clinical urine of colorectal cancer.

Asia Pac J Clin Oncol 2021 Aug 23;17(4):403-413. Epub 2021 Jun 23.

China-Japan Friendship Hospital, Beijing, China.

Aim: To demonstrate the little-known metabolic changes and pathways in patients with colorectal cancer (CRC).

Methods: We used gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) to perform metabolic profiling of urine samples from 163 consecutive patients with CRC and 111 healthy controls without history of gastrointestinal tumors. The metabolic profiles were assayed using multivariate statistical analysis and one-way analysis of variance, and further analyzed to identify potential marker metabolites related to CRC. The GC-TOF/MS-derived models showed clear discriminations in metabolic profiles between the CRC group and healthy control group.

Results: We demonstrated that 15 metabolites contributed to the differences. Among them, eleven metabolites were significantly upregulated, while other four metabolites were downregulated in the urine samples of CRC patients compared with healthy controls. Pathway analysis revealed changes in energy metabolism of patients with CRC, which are reflected in the upregulation of glycolysis and amino acid metabolism and the downregulation of lipid metabolism. Our study revealed the metabolic profile of urine from CRC patients and indicated that GC-TOF/MS-based methods can distinguish CRC from healthy controls.

Conclusion: GC-TOF/MS-based metabolomics has the potential to be developed into a novel, non-invasive, and painless clinical tool for CRC diagnosis, and may contribute to an improved understanding of disease mechanisms.
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http://dx.doi.org/10.1111/ajco.13591DOI Listing
August 2021

PDL1-positive exosomes suppress antitumor immunity by inducing tumor-specific CD8 T cell exhaustion during metastasis.

Cancer Sci 2021 Sep 29;112(9):3437-3454. Epub 2021 Jul 29.

Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China.

Metastasis is the main cause of death in individuals with cancer. Immune checkpoint blockade (ICB) can potentially reverse CD8 cytotoxic T lymphocytes (CTLs) dysfunction, leading to significant remission in multiple cancers. However, the mechanism underlying the development of CTL exhaustion during metastatic progression remains unclear. Here, we established an experimental pulmonary metastasis model with melanoma cells and discovered a critical role for melanoma-released exosomes in metastasis. Using genetic knockdown of nSMase2 and Rab27a, 2 key enzymes for exosome secretion, we showed that high levels of effector-like tumor-specific CD8 T cells with transitory exhaustion, instead of terminal exhaustion, were observed in mice without exosomes; these cells showed limited inhibitory receptors and strong proliferation and cytotoxicity. Mechanistically, the immunosuppression of exosomes depends on exogenous PD-L1, which can be largely rescued by pretreatment with antibody blockade. Notably, we also found that exosomal PD-L1 acts as a promising predictive biomarker for ICB therapies during metastasis. Together, our findings suggest that exosomal PD-L1 may be a potential immunotherapy target, suggesting a new curative therapy for tumor metastasis.
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http://dx.doi.org/10.1111/cas.15033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409314PMC
September 2021

Insights into the mechanisms underlying opioid use disorder and potential treatment strategies.

Br J Pharmacol 2021 Jun 14. Epub 2021 Jun 14.

Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.

Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the opioid receptor system and those that target non-opioid receptor systems, including the dopamine and glutamate receptor systems. Currently, the clinical drugs used to treat opioid use disorder include the opioid receptor agonists methadone and buprenorphine, which are limited by their abuse liability, and the opioid receptor antagonist naltrexone, which is limited by poor compliance. Therefore, the development of effective medications with lower abuse liability and better potential for compliance is urgently needed. Based on recent advances in the understanding of the neurobiological mechanisms underlying opioid use disorder, potential treatment strategies and targets have emerged. This review focuses on the progress made in identifying potential targets and developing medications to treat opioid use disorder, including progress made by our laboratory, and provides insights for future medication development.
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http://dx.doi.org/10.1111/bph.15592DOI Listing
June 2021

A Multi-Phase Based Multi-Application Mapping Approach for Many-Core Networks-on-Chip.

Micromachines (Basel) 2021 May 26;12(6). Epub 2021 May 26.

College of Electronic and Information Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.

More and more attention is being paid to the use of massive parallel computing performed on many-core Networks-on-Chip (NoC) in order to accelerate performance. Simultaneously deploying multiple applications on NoC is one feasible way to achieve this. In this paper, we propose a multi-phase-based multi-application mapping approach for NoC design. Our approach began with a rectangle analysis, which offered several potential regions for application. Then we mapped all tasks of the application into these potential regions using a genetic algorithm, and identified the one which exhibited the strongest performance. When the packeted regions for each application were identified, a B*Tree-based simulated annealing algorithm was used to generate the optimal placement for the multi-application mapping regions. The experiment results show that the proposed approach can achieve a considerable reduction in network power consumption (up to 23.45%) and latency (up to 24.42%) for a given set of applications.
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http://dx.doi.org/10.3390/mi12060613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227643PMC
May 2021

Suction feeding by elephants.

J R Soc Interface 2021 06 2;18(179):20210215. Epub 2021 Jun 2.

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Despite having a trunk that weighs over 100 kg, elephants mainly feed on lightweight vegetation. How do elephants manipulate such small items? In this experimental and theoretical investigation, we filmed elephants at Zoo Atlanta showing that they can use suction to grab food, performing a behaviour that was previously thought to be restricted to fishes. We use a mathematical model to show that an elephant's nostril size and lung capacity enables them to grab items using comparable pressures as the human lung. Ultrasonographic imaging of the elephant sucking viscous fluids show that the elephant's nostrils dilate up to [Formula: see text] in radius, which increases the nasal volume by [Formula: see text]. Based on the pressures applied, we estimate that the elephants can inhale at speeds of over 150 m s, nearly 30 times the speed of a human sneeze. These high air speeds enable the elephant to vacuum up piles of rutabaga cubes as well as fragile tortilla chips. We hope these findings inspire further work in suction-based manipulation in both animals and robots.
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http://dx.doi.org/10.1098/rsif.2021.0215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169210PMC
June 2021

Structural characteristics and immune-enhancing activity of an extracellular polysaccharide produced by marine Halomonas sp. 2E1.

Int J Biol Macromol 2021 Jul 25;183:1660-1668. Epub 2021 May 25.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Microbial polysaccharides from extreme environments, such as cold seeps and hydrothermal vents, usually exhibit novel structural features and diverse biological activities. In this study, an exopolysaccharide (EPS2E1) was isolated from cold-seep bacterium Halomonas sp. 2E1 and its immune-enhancing activity was evaluated. The total sugar content and protein content were determined as 83.1% and 7.9%, respectively. EPS2E1 contained mannose and glucose with the molar ratio of 3.76: 1. The molecular weight was determined to be 47.0 kDa. Structural analysis indicated that EPS2E1 was highly branched, the backbone mainly consisted of →2)-Man-(α-1→ and →2, 6)-Man-(α-1→ with the ratio of 2.45: 1.00. The chain also contained →4)-Glc-(α-1→, →6)-Man-(α-1→ and →3)-Glc-(β-1→. EPS2E1 could significantly increase the production of NO, COX-2, TNF-α, IL-1β and IL-6 by activating the MAPK and NF-κB pathways on RAW264.7 macrophages. EPS2E1 exhibits the potential to be an immunopotentiator in the near future.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.143DOI Listing
July 2021
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