Publications by authors named "Yuqing Wang"

258 Publications

Smoothened is a therapeutic target for reducing glutamate toxicity in ischemic stroke.

Sci Transl Med 2021 Sep 8;13(610):eaba3444. Epub 2021 Sep 8.

The Brain Science Center, Beijing Institute of Basic Medical Sciences, 100850 Beijing, China.

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http://dx.doi.org/10.1126/scitranslmed.aba3444DOI Listing
September 2021

Etiologies of Hospitalized Acute Bronchiolitis in Children 2 Years of Age and Younger: A 3 Years' Study During a Epidemic.

Front Pediatr 2021 12;9:621381. Epub 2021 Aug 12.

Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, China.

In recent years, the incidence of infection in infants and young children has been increasing. Multiple studies have suggested that may be one of the pathogens of bronchiolitis in infants and young children. However, the prevalence and clinic characteristic of in bronchiolitis is controversial. This prospective descriptive study evaluated the prevalence and clinical manifestations of infants and young children hospitalized for bronchiolitis with . Children hospitalized with bronchiolitis were eligible for a prospective study for 36 months from January 1, 2017, to December 31, 2019. Besides , 10 common respiratory viruses and (MP) were confirmed by laboratory tests. Medical records of patients were reviewed for demographic, clinical characteristics, and laboratory examination. A total of 1,092 patients with bronchiolitis were admitted. was detected in 78/1,092 (7.1%) patients. Of the 78 patients with bronchiolitis, coinfections occurred in 45 (57.7%) patients, most frequently with human rhinovirus (28/78, 35.9%), followed by MP (9/78, 11.4%), and human bocavirus (6/78, 7.7%). The peak incidence of infection was in May. A high leukocyte count could help distinguish associated acute bronchiolitis from other acute bronchiolitis etiologies. After excluding coinfections, children with only bronchiolitis exhibited a milder clinical presentation than those with RSV-only infection; also, children with MP-only and other pathogen infections revealed similar severity. The morbidity of was common (31/78, 39.7%) in infants with bronchiolitis under 3 months. In summary, is one of the pathogens in children with bronchiolitis, and coinfection of with other viruses is common in bronchiolitis. should be considered when patients hospitalized with bronchiolitis present a longer course and have an elevated leukocyte count. Patients with associated bronchiolitis present a milder clinical presentation.
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http://dx.doi.org/10.3389/fped.2021.621381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397516PMC
August 2021

Practicable Applications of Aggregation-Induced Emission with Biomedical Perspective.

Adv Healthc Mater 2021 Aug 21:e2100945. Epub 2021 Aug 21.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, China.

Considerable efforts have been made into developing aggregation-induced emission fluorogens (AIEgens)-containing nano-therapeutic systems due to the excellent properties of AIEgens. Compared to other fluorescent molecules, AIEgens have advantages including low background, high signal-to-noise ratio, good sensitivity, and resistance to photobleaching, in addition to being exempt from concentration quenching or aggregation-caused quenching effects. The present review outlines the major developments in the biomedical applications of AIEgens-containing systems. From a literature survey, the recent AIE works are reviewed and the reasons why AIEgens are chosen in various biomedical applications are highlighted. The research activities on AIEgens-containing systems are increasing rapidly, therefore, the present review is timely.
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http://dx.doi.org/10.1002/adhm.202100945DOI Listing
August 2021

Recent Progress in Emerging Two-Dimensional Transition Metal Carbides.

Nanomicro Lett 2021 Aug 20;13(1):183. Epub 2021 Aug 20.

Interdisciplinary Nanoscience Center, Aarhus University, 8000, Aarhus, Denmark.

As a new member in two-dimensional materials family, transition metal carbides (TMCs) have many excellent properties, such as chemical stability, in-plane anisotropy, high conductivity and flexibility, and remarkable energy conversation efficiency, which predispose them for promising applications as transparent electrode, flexible electronics, broadband photodetectors and battery electrodes. However, up to now, their device applications are in the early stage, especially because their controllable synthesis is still a great challenge. This review systematically summarized the state-of-the-art research in this rapidly developing field with particular focus on structure, property, synthesis and applicability of TMCs. Finally, the current challenges and future perspectives are outlined for the application of 2D TMCs.
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http://dx.doi.org/10.1007/s40820-021-00710-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379312PMC
August 2021

Comment on "Altered Expression of Long Non-coding RNAs in Peripheral Blood Mononuclear Cells of Patients with Alzheimer's Disease".

Mol Neurobiol 2021 Aug 14. Epub 2021 Aug 14.

School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.

We read with great interest the article by Kurt and colleagues. The authors, using microarray in clinical samples, found altered expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) of patients with Alzheimer's disease (AD). The findings from this study may open a door to the understanding of AD pathogenesis targeted by lncRNAs. In our opinion, it is necessary to further clarify the data analysis strategy of this study. According to the authors' description, they seem to use unadjusted p values and fold change of expression values when defining significantly differentially expressed lncRNAs in PBMCs of subjects with probable AD and healthy control groups. However, due to the characteristics of lncRNA and high false positives caused by multiple comparisons, t-test is not suitable for high-level microarray analysis. It seems that a specialized high-level microarray analysis method is essential to reach a reliable result. Accurate analysis results will provide a convincing basis for subsequent experiments.
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http://dx.doi.org/10.1007/s12035-021-02513-8DOI Listing
August 2021

A novel mechanism of enhanced transcription activity and fidelity for influenza A viral RNA-dependent RNA polymerase.

Nucleic Acids Res 2021 09;49(15):8796-8810

The Hong Kong University of Science and Technology-Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China.

During RNA elongation, the influenza A viral (IAV) RNA-dependent RNA polymerase (RdRp) residues in the active site interact with the triphosphate moiety of nucleoside triphosphate (NTP) for catalysis. The molecular mechanisms by which they control the rate and fidelity of NTP incorporation remain elusive. Here, we demonstrated through enzymology, virology and computational approaches that the R239 and K235 in the PB1 subunit of RdRp are critical to controlling the activity and fidelity of transcription. Contrary to common beliefs that high-fidelity RdRp variants exert a slower incorporation rate, we discovered a first-of-its-kind, single lysine-to-arginine mutation on K235 exhibited enhanced fidelity and activity compared with wild-type. In particular, we employed a single-turnover NTP incorporation assay for the first time on IAV RdRp to show that K235R mutant RdRp possessed a 1.9-fold increase in the transcription activity of the cognate NTP and a 4.6-fold increase in fidelity compared to wild-type. Our all-atom molecular dynamics simulations further elucidated that the higher activity is attributed to the shorter distance between K235R and the triphosphate moiety of NTP compared with wild-type. These results provide novel insights into NTP incorporation and fidelity control mechanisms, which lay the foundation for the rational design of IAV vaccine and antiviral targets.
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http://dx.doi.org/10.1093/nar/gkab660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421151PMC
September 2021

Synthesis of the Proposed Structures of Parvistemoamide and Their Transformations to Stemoamide Derivatives.

Org Lett 2021 Aug 9;23(16):6222-6226. Epub 2021 Aug 9.

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Ministry of Education of China, Lanzhou 730000, Gansu, China.

The proposed structures of parvistemoamide have been achieved by macrolactamization, but none of the characterization data of synthetic samples matched with those of the natural sample. The transformation of the highly strained 10-membered lactam ring in parvistemoamide into the pyrrolo[1,2-]-azepine nucleus in stemoamide is accomplished for the first time by either transannular cyclization or Pilli's transformation. This research may promote the total synthesis of other more complex stemoamide-type or medium-sized-ring-containing alkaloids.
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http://dx.doi.org/10.1021/acs.orglett.1c01045DOI Listing
August 2021

Storage Mechanism of Alkali Metal Ions in the Hard Carbon Anode: an Electrochemical Viewpoint.

ACS Appl Mater Interfaces 2021 Aug 3;13(32):38441-38449. Epub 2021 Aug 3.

School of Materials Science and Engineering, Key Laboratory of Advanced Ceramics and Machining Technology (Ministry of Education), and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China.

The storage mechanisms of Li, Na, and K in hard carbon anodes are investigated through systematically exploring their electrochemical behaviors. Two charge/discharge voltage regions are observed for all the Li, Na, and K storage, a slope at a high voltage, and a plateau in a low-voltage range. Considerably different behaviors are revealed by the galvanostatic intermittent titration technique and electrochemical impedance spectroscopy measurements, and accordingly different storage mechanisms are proposed. The sloping region is mainly attributed to the adsorption at defects/heteroatoms for all the Li, Na, and K storage. In the plateau region, pore filling contributes very little to Li storage but much to Na and K storage. Furthermore, significant effects of ionic sizes on the storage behavior in hard carbons are revealed by the electrochemical performance from Li to Na to K. These findings not only offer a fundamental understanding of storage mechanisms of alkali metal ions in hard carbons but also help develop and design innovative electrode materials for low-cost and large-scale energy storage systems.
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http://dx.doi.org/10.1021/acsami.1c12150DOI Listing
August 2021

High-Performance Polymeric Lithium Salt Electrode Material from Phenol-Formaldehyde Condensation.

ACS Appl Mater Interfaces 2021 Aug 2;13(31):37289-37298. Epub 2021 Aug 2.

Hubei Key Lab of Electrochemical Power Sources, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.

In spite of the recent progress made in organic electrode materials, high-performance candidates are still lacking, especially when taking affordability into account. Herein, we report a novel polymeric lithium salt, namely dilithium salt of poly(2,5-dihydroxy-1,4-benzoquinone-3,6-methylene) (LiPDBM), which can be easily synthesized by phenol-formaldehyde condensation, followed by lithiation in LiOH solution to eliminate the negative effect of phenol groups in PDBM. Benefiting from a high theoretical capacity (327 mA h g), structure stability, insolubility, and redox reversibility, LiPDBM exhibits superior electrochemical performance as a cathode for rechargeable lithium batteries, including a high reversible capacity (256 mA h g), a high rate capability (79% @ 2000 mA g), and a high cycling stability (77% @ 2000th cycle). Besides the cost-effective electrode material synthesis approach, this work also provides an important mechanistic understanding of the structure-performance relationship of carbonyl-based electrode materials, especially those with -OH or -OM (M = Li, Na, and K) substituents.
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http://dx.doi.org/10.1021/acsami.1c11687DOI Listing
August 2021

First-principles Insights into Cu-Decorated GaN Monolayers for Sensing CO and HCHO in Dry-Type Transformers.

ACS Omega 2021 Jul 14;6(29):19127-19133. Epub 2021 Jul 14.

China Electric Power Research Institute, Wuhan 430074, China.

This work using first-principles theory studies the sensing properties of Cu-decorated GaN (Cu-GaN) monolayers as a promising candidate for the detection of CO and HCHO in dry-type transformers. The Cu dopant prefers to be trapped on the T site of the GaN surface with an of -1.13 eV. Chemisorption is identified for the two gas adsorption systems, given the large adsorption energy ( ) of -1.35 and -1.09 eV. Caused by the chemisorption, the electronic property of the Cu-GaN monolayer is significantly deformed, narrowing its band gap of 0.548 eV to 0.00 eV, exhibiting metallic property, in two gas systems. Combined with the desirable recovery property for CO and HCHO desorption from the Cu-GaN surface, it could be proposed that the Cu-GaN monolayer is a promising gas sensor for toxic gas detection in dry-type transformers, so as to evaluate the operation status of the power system and guarantee safe working conditions for the maintenances.
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http://dx.doi.org/10.1021/acsomega.1c02474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320106PMC
July 2021

LncRNA HOTAIR promotes proliferation and inhibits apoptosis by sponging miR-214-3p in HPV16 positive cervical cancer cells.

Cancer Cell Int 2021 Jul 28;21(1):400. Epub 2021 Jul 28.

Demonstration Center for Experimental Basic Medicine Education, Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.

Background: Cervical cancer (CC) is one of the most common gynaecological malignancies all around the world. The mechanisms of cervical carcinoma formation remain under close scrutiny. The long non-coding RNAs (lncRNA) and microRNAs (miRNAs) play important roles in controlling gene expression and promoting the development and progression of cervical cancer by acting as competitive endogenous RNA (ceRNA). However, the roles of lncRNA associated with ceRNAs in cervical carcinogenesis remains unknown. In this study, the expression of long non-coding RNA HOTAIR was investigated in HPV16 positive cervical cancer cells, the candidate miRNAs and target genes were identified to clarify putative ceRNAs of HOTAIR/miRNA in cervical cancer cells.

Methods: The proliferation ability of cells was measured by CCK8 and EdU incorporation assays and cell apoptosis was analyzed by flow cytometry. The expression of HOTAIR, miR-214-3p, HPV16 E7 mRNA were detected by qRT-PCR. As for searching for the interaction between miR-214-3p and HOTAIR, the binding sites for miR-214-3p on HOTAIR was predicted by starbase v2.0 database, then dual-luciferase assay was used to verify the binding sites. In addition, Gene Ontology (GO) and protein-protein interaction (PPI) network analysis of target genes of miR-214-3p were performed with bioinformatics analysis. The potential signal pathway regulated by HOTAIR/miR-214-3p was predicted by KEGG enrichment analysis and confirmed by qPCR and WB analysis in cervical cancer cells.

Results: Our results showed that expression of HOTAIR was up-regulated, while that of miR-214-3p was down-regulated in HPV16-positive cervical cancer cells. The expression status of HPV16 E7 played an important role in regulating expression of HOTAIR or miR-214-3p in cervical cancer cells. HOTAIR knockdown could significantly inhibited cell proliferate ability and promote cellular apoptosis, whereas the inhibition of miR-214-3p expression partially reversed such results. Bioinformatics analysis identified 1451 genes as target genes of miR-214-3p. The Gene ontology (GO) and KEGG Pathway enrichment analysis showed that these target genes were mainly related to regulation of cell communication, protein binding, enzyme binding and transferase activity, and Wnt ligand biogenesis. Pathway enrichment analysis results showed that the predicted target genes were significantly enriched in Wnt/β-catenin signaling pathway. Finally, our results confirmed that miR-214-3p could significantly inhibit β-catenin expression in HPV16 positive cancer cells by qPCR and WB analysis.

Conclusion: HOTAIR could act as a ceRNA through binding to miR-214-3p, promote cell proliferation and inhibit the apoptosis of HPV16 positive cervical cancer. HOTAIR/miR-214-3p/Wnt/β-catenin signal pathway might played important regulated roles in HPV16 positive cervical cancer. Our results provided new insight into defining novel biomarkers for cervical cancer.
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http://dx.doi.org/10.1186/s12935-021-02103-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317292PMC
July 2021

Mapping annual land disturbance and reclamation in rare-earth mining disturbance region using temporal trajectory segmentation.

Environ Sci Pollut Res Int 2021 Jul 21. Epub 2021 Jul 21.

School of Civil and Surveying & Mapping Engineering, Jiangxi University of Science and Technology, Ganzhou, 341000, China.

Rare-earth mining has caused extensive damage to soil, vegetation, and water, significantly threatening ecosystems. Monitoring environmental disturbance caused by rare-earth mining is necessary to protect the ecological environment. A spatiotemporal remote sensing monitoring method for mining to reclamation processes in a rare-earth mining area using multisource time-series satellite images is described. In this study, the normalized difference vegetation index (NDVI) is used to evaluate the mining impact. Regression analysis is conducted to relate the HJ-1B CCD and Landsat 5/8 data to reduce the NDVI error related to sensor differences between different datasets. The analysis method of NDVI trajectory data of ground objects is proposed, and areas of environmental disturbance caused by rare-earth mining are identified. Pixel-based trajectories were used to reconstruct the temporal evolution of vegetation, and a temporal trajectory segmentation method is established based on the vegetation changes in different disturbance stages. The temporal trajectory of the rare-earth disturbance points is segmented to extract features in each stage to obtain the disturbance year, recovery year, and recovery cycle and evaluate the vegetation recovery after rare-earth mining disturbance. We applied the method to a stack of 20 multitemporal images from 2000 to 2019 to analyze vegetation disturbance due to rare-earth mining and vegetation recovery in the upper reaches of the Guangdong-Hong Kong-Macao Greater Bay Area, China. The results show the following. (1) Mining industry in the study area experienced rapid expansion before 2008, but growth slowed since the policies implemented by the government since 2009 to restrict rare-earth mining. (2) The continuous influence to the land caused by rare-earth mining can last for decades; however, the reclamation activities shorten the recovery cycle of mining land from 5 to 3 years.
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http://dx.doi.org/10.1007/s11356-021-15480-3DOI Listing
July 2021

Macrophage Polarization in Response to Biomaterials for Vascularization.

Ann Biomed Eng 2021 Jul 19. Epub 2021 Jul 19.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, People's Republic of China.

Vascularization of tissue engineering constructs is an urgent need for delivering oxygen and nutrients and promoting tissue remodeling. As we all know, almost all implanted biomaterials elicit immune responses. Interestingly, the immunomodulatory biomaterials can utilize the inherent regenerative capability of endogenous cells and stem cells recruited by the activated immune cells to facilitate anagenesis and tissue remodeling. Macrophages, as almost ones of the first responses upon the implantation of biomaterials, play a vital role in guiding vascular formation and tissue remodeling. The polarization of macrophages can be influenced by the physical and chemical properties of biomaterials and thus they display diverse function states. Here, this review focus on the macrophage polarization in response to biomaterials and the interactions between them. It also summarizes the current strategies to promote vascularization of tissue engineering constructs through macrophage responses.
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http://dx.doi.org/10.1007/s10439-021-02832-wDOI Listing
July 2021

Growth and development of children under 5 years of age with tetralogy of Fallot in a Chinese population.

Sci Rep 2021 Jul 9;11(1):14255. Epub 2021 Jul 9.

Shandong Collaborative Innovation Center for Diagnosis, Treatment and Behavioral Interventions of Mental Disorders, Institute of Mental Health, Jining Medical University, Jining, China.

Congenital Heart Defects (CHDs) are associated with different patterns of malnutrition and growth retardation, which may vary worldwide and need to be evaluated according to local conditions. Although tetralogy of Fallot (TOF) is one of the first described CHDs, the etiology outcomes in growth and development of TOF in early age child is still unclear in most cases. This study was designed to investigate the growth retardation status of Chinese pediatric TOF patients under 5 years old. The body height, body weight and body mass index (BMI) of 262 pediatric patients (138 boys and 124 girls) who underwent corrective surgery for TOF between 2014 and 2018 were measured using conventional methods. The average body height, body weight and BMI of the patients were significantly lower than WHO Child Growth Standards, while the most affected was body height. Meanwhile, higher stunting frequency and greater deterioration of both the body height and weight happened in elder age (aged 13-60 months) rather than in infant stage (aged 0-12 months) among these patients. Our results confirmed that intervention should be given at early age to prevent the growth retardation of TOF patients getting severer.
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http://dx.doi.org/10.1038/s41598-021-93726-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271005PMC
July 2021

The mechanism of action of T-705 as a unique delayed chain terminator on influenza viral polymerase transcription.

Biophys Chem 2021 Oct 25;277:106652. Epub 2021 Jun 25.

The Hong Kong University of Science and Technology-Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China; Bioengineering Graduate Program, Department of Biological and Chemical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong; Department of Chemistry, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Kowloon, Hong Kong. Electronic address:

Favipiravir (T-705) has been developed as a potent anti-influenza drug and exhibited a strong inhibition effect against a broad spectrum of RNA viruses. Its active form, ribofuranosyl-triphosphate (T-705-RTP), functions as a competitive substrate for the RNA-dependent RNA polymerase (RdRp) of the influenza A virus (IAV). However, the exact inhibitory mechanisms of T-705 remain elusive and subject to a long-standing debate. Although T-705 has been proposed to inhibit transcription by acting as a chain terminator, it is also paradoxically suggested to be a mutagen towards IAV RdRp by inducing mutations due to its ambiguous base pairing of C and U. Here, we combined biochemical assay with molecular dynamics (MD) simulations to elucidate the molecular mechanism underlying the inhibitory functions exerted by T-705 in IAV RdRp. Our in vitro transcription assay illustrated that IAV RdRp could recognize T-705 as a purine analogue and incorporate it into the nascent RNA strand. Incorporating a single T-705 is incapable of inhibiting transcription as extra natural nucleotides can be progressively added. However, when two consecutive T-705 are incorporated, viral transcription is completely terminated. MD simulations reveal that the sequential appearance of two T-705 in the nascent strand destabilizes the active site and disrupts the base stacking of the nascent RNA. Altogether, our results provide a plausible explanation for the inhibitory roles of T-705 targeting IAV RdRp by integrating the computational and experimental methods. Our study also offers a comprehensive platform to investigate the inhibition effect of antivirals and a novel explanation for the designing of anti-flu drugs.
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http://dx.doi.org/10.1016/j.bpc.2021.106652DOI Listing
October 2021

Li Maneuver for geotropic horizontal canal benign paroxysmal positional vertigo (HC-BPPV) -A better choice.

Am J Otolaryngol 2021 Sep-Oct;42(5):103132. Epub 2021 Jun 19.

Department of Otolaryngology Head and Neck Surgery, Sixth Medical Center of PLA General Hospital, China.

Purpose: This study aimed to retrospectively evaluate the efficacy of Li Maneuver as a repositioning maneuver for geotropic HC-BPPV, compared with Gufon Maneuver.

Methods: Data of geotropic HC-BPPV patients treated at our department between January 2009 and January 2020 was retrospectively collected and analyzed. Enrolled cases were divided into Gufoni Group and Li Group. Follow-up results were recorded on the first, third, and seventh day after the first therapeutic maneuver.

Results: A total of 254 cases were enrolled, with 87 cases in Gufoni Group, and 167 cases in Li Group. The cure rate at the first, third, and seventh days of follow-up was 62.22%, 77.01%, and 90.80% respectively for Gufoni Group, while for Li Group the number was 60.48%, 72.46%, and 89.22% respectively. Statistical analysis showed no significant difference.

Conclusions: Li Maneuver for geotropic HC-BPPV was as effective as Gufoni Maneuver but much simpler and faster. By introducing Li Maneuver, we may help physicians to treat geotropic HC-BPPV patients more willingly, which would decrease the chance of delayed treatment and ease the burden of the health-care system.
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http://dx.doi.org/10.1016/j.amjoto.2021.103132DOI Listing
June 2021

Hsa_circ_0005915 promotes N,N-dimethylformamide-induced oxidative stress in HL-7702 cells through NRF2/ARE axis.

Toxicology 2021 06 19;458:152838. Epub 2021 Jun 19.

Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

N,N-dimethylformamide (DMF) is an organic compound widely used in industrial production processes as a solvent with a low evaporation rate. Excessive exposure to DMF may lead to liver damage. Oxidative stress has been reported as one of the main causes of DMF-induced hepatotoxicity. Several doses of DMF (0, 1, 5, and 10 mM) were used to treat HL-7702 cells for a relatively long period to simulate the actual exposure pattern in occupational settings, and oxidative stress was induced. Previous studies illustrated that circular RNA (circRNA) plays a vital role in sustaining hepatocyte physiological function. To explore whether aberrant circRNA expression is involved in DMF-induced excessive ROS generation and hepatotoxicity, high-throughput transcriptional sequencing was performed to identify the altered circRNA expression profiles in HL-7702 liver cells after treatment with 0, 75, or 150 mM DMF for 48 h. We found that levels of induced oxidative stress were similar to those in the long-term exposure model. Among the altered circRNAs, one circRNA (hsa_circ_0005915) was significantly upregulated after DMF exposure, and it affected DMF-mediated oxidative stress in HL-7702 cells. Further experiments revealed that hsa_circ_0005915 downregulated the expression of nuclear factor erythoid-2-related factor 2 (NRF2) at the post-transcriptional level via promoting the ubiquitination and degradation of NRF2, which led to the increase of ROS accumulation. Further investigation demonstrated that the expression levels of NRF2-regulated antioxidative genes-heme oxygenase 1 (HO1) and NAD(P)H quinone dehydrogenase 1 (NQO1)-indeed declined after the overexpression of hsa_circ_0005915. In vivo study also indicated that DMF exposure can upregulate the expression of mmu_circ_0007941 (homologous circRNA of hsa_circ_0005915) and downregulated Nrf2 and Ho1 proteins. In summary, our results revealed that hsa_circ_0005915 plays an important role in promoting DMF-induced oxidative stress by inhibiting the transcriptional activity of the NRF2/ARE axis, which provides a potential molecular mechanism of DMF-mediated hepatotoxicity.
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http://dx.doi.org/10.1016/j.tox.2021.152838DOI Listing
June 2021

Broadband plasmon-induced transparency modulator in the terahertz band based on multilayer graphene metamaterials.

J Opt Soc Am A Opt Image Sci Vis 2021 Jun;38(6):784-789

In this study, multilayer graphene metamaterials comprising graphene blocks and graphene ribbon are proposed to realize dynamic plasmon-induced transparence (PIT). By changing the position between the graphene blocks, PIT phenomenon will occur in different terahertz bands. Furthermore, PIT with a transparent window width of 1 THz has been realized. In addition, the PIT shows redshifts or blueshifts or disappears altogether upon changing the Fermi level of graphene, and hence a frequency selector from 3.91 to 7.84 THz and an electro-optical switch can be realized. Surprisingly, the group index of this structure can be increased to 469. Compared with the complex and fixed structure of previous studies, our proposed structure is simple and can be dynamically adjusted according to demands, which makes it a valuable platform for ideas to inspire the design of novel electro-optic devices.
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http://dx.doi.org/10.1364/JOSAA.420743DOI Listing
June 2021

Decitabine Sensitizes the Radioresistant Lung Adenocarcinoma to Pemetrexed Through Upregulation of Folate Receptor Alpha.

Front Oncol 2021 17;11:668798. Epub 2021 May 17.

Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, China.

Chemotherapy is the backbone of subsequent treatment for patients with lung adenocarcinoma (LUAD) exhibiting radiation resistance, and pemetrexed plays a critical role in this chemotherapy. However, few studies have assessed changes in the sensitivity of LUAD cells to pemetrexed under radioresistant circumstances. Therefore, the objectives of this study were to delineate changes in the sensitivity of radioresistant LUAD cells to pemetrexed and to elucidate the related mechanisms and then develop an optimal strategy to improve the cytotoxicity of pemetrexed in radioresistant LUAD cells. Our study showed a much lower efficacy of pemetrexed in radioresistant cells than in parental cells, and the mechanism of action was the significant downregulation of folate receptor alpha (FRα) by long-term fractionated radiotherapy, which resulted in less cellular pemetrexed accumulation. Interestingly, decitabine effectively reversed the decrease in FRα expression in radioresistant cells through an indirect regulatory approach. Thereafter, we designed a combination therapy of pemetrexed and decitabine and showed that the activation of FRα by decitabine sensitizes radioresistant LUAD cells to pemetrexed both and in xenografts. Our findings raised a question regarding the administration of pemetrexed to patients with LUAD exhibiting acquired radioresistance and accordingly suggested that a combination of pemetrexed and decitabine would be a promising treatment strategy.
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http://dx.doi.org/10.3389/fonc.2021.668798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165306PMC
May 2021

2-Mercaptoethanol (2-ME)-based IATs or Polybrene method mitigates the interference of daratumumab on blood compatibility tests.

Hematology 2021 Dec;26(1):365-370

Department of Blood Transfusion, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China.

Objectives: Treating red blood cells (RBCs) with dithiothreitol (DTT) is a wildly-recommended to overcome the interference of the daratumumab (DARA) with blood compatibility testing. Nevertheless, DTT can be hard to obtain in the clinical laboratory, while its use in routine practice may be time-consuming. In the following study, we explored the feasibility of using a commercial 2-mercaptoethanol (2-ME) working solution or the time-saving Polybrene method to mitigate DARA interference.

Methods: Antibody screening and cross-matching were performed using 2-ME or DTT-based indirect antiglobulin tests (IATs) and Polybrene method (with human IgG anti-E same IATs titer as DARA as positive control) on 37 samples. Most clinically important blood group antigens on RBCs were detected after treatment with 2-ME or DTT.

Results: Treating RBCs with 2-ME eliminates the DARA interference with the antibody screening or cross-matching; yet, K antigen is denatured during treatment. DARA does not interfere with antibody screening and cross-matching via Polybrene method, while 2+ agglutinations of anti-E antibody with the same titer (IATs method) as DARA could be observed in the positive controls via this method.

Conclusion: 2-ME-based IATs or Polybrene method could replace DTT-based IATs to mitigate DARA interference.
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http://dx.doi.org/10.1080/16078454.2021.1918916DOI Listing
December 2021

A predictive study of multivariate factors affecting goal attainment of INR after anticoagulation in patients with nonvalvular atrial fibrillation.

Ann Palliat Med 2021 Apr;10(4):4532-4538

Department of Cardiovascular Medicine, Xinqiao Hospital Affiliated to Army Military Medical University, Chonqing, China.

Background: Non-valvular atrial fibrillation (NVAF) is a common type of AF, and patients with NVAF have a higher risk of ischemic stroke than non-AF patients. This study aims to investigate the goal attainment of international normalized ratio (INR) in patients with NVAF after anticoagulation therapy, and to analyze the risk factors that affect the goal attainment of INR.

Methods: NVAF patients who were admitted to our hospital from December 2019 to December 2020 and received anticoagulation therapy were selected as the research subjects. The INR goal attainment of patients was assessed, the risk factors affecting INR goal attainment were analyzed, and a ROC curve was drawn to evaluate the predictive value of risk factors for INR goal attainment in NVAF patients.

Results: After anticoagulation treatment, the INR of 42 cases reached the target (INR value ≥0.2, the goal attainment group), and the INR of 74 cases did not reach the target (INR value <2.0, the non-goal attainment group). The age, mean platelet volume (MPV), platelet distribution width (PDW), and large platelet ratio (P-LCR) levels of patients in the goal attainment group were significantly lower than those in the non-goal attainment group, and the platelet count (PLT) level was higher than that of the non-goal attainment group (P<0.05). The results of multivariate logistic regression analysis showed that MPV, PDW, and P-LCR were independent risk factors that affected the failure in INR goal attainment in patients with NVAF after anticoagulation therapy. The ROC curve showed that the AUC values of MPV, PDW, and P-LCR were 0.711, 0.748, 0.867, respectively, and the combined AUC was 0.876, which was higher than that of the single detection.

Conclusions: MPV, PDW, and P-LCR are important factors that affect the goal attainment of INR after anticoagulant therapy in NVAF patients. For patients with risk factors, clinicians can formulate a reasonable individualized anticoagulant drug regimen based on the above-mentioned index levels.
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http://dx.doi.org/10.21037/apm-21-549DOI Listing
April 2021

Lysozyme Adsorption on Different Functionalized MXenes: A Multiscale Simulation Study.

Langmuir 2021 05 7;37(19):5932-5942. Epub 2021 May 7.

School of Chemistry and Chemical Engineering, Guangdong Provincial Key Lab for Green Chemical Product Technology, South China University of Technology, Guangzhou 510640, P. R. China.

Recently, MXenes, due to their abundant advantages, have been widely applied in energy storage, separation, catalysis, biosensing, et al. In this study, parallel tempering Monte Carlo and molecular dynamics methods were performed to investigate lysozyme adsorption on different functionalized TiCT (-O, -OH, and -F). The simulation results show that lysozyme can adsorb effectively on TiCT surfaces, and the order of interaction strength is TiCO > TiCF > TiC(OH). Electrostatics together with van der Waals interactions control protein adsorption. The orientation distributions of lysozyme adsorbed on the TiCO and TiCF surfaces are more concentrated than that on the TiC(OH) surface. During adsorption, the conformation of lysozyme remains stable, suggesting the good biocompatibility of TiCT. Besides, the distribution of the interfacial water layer on the TiCT surface has a certain impact on protein adsorption. This study provides theoretical insights for understanding the biocompatibility of 2D TiCT materials and may help us evaluate the engineering of their surfaces for future biorelated applications.
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http://dx.doi.org/10.1021/acs.langmuir.1c00480DOI Listing
May 2021

Hepatoid Adenocarcinoma of the Stomach: Current Perspectives and New Developments.

Front Oncol 2021 12;11:633916. Epub 2021 Apr 12.

Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignant tumor, accounting for only 0.17-15% of gastric cancers. Patients are often diagnosed at an advanced disease stage, and their symptoms are similar to conventional gastric cancer (CGC) without specific clinical manifestation. Morphologically, HAC has identical morphology and immunophenotype compared to hepatocellular carcinoma (HCC). This is considered to be an underestimation in diagnosis due to its rare incidence, and no consensus is reached regarding therapy. HAS generally presents with more aggressive behavior and worse prognosis than CGC. The present review summarizes the current literature and relevant knowledge to elaborate on the epidemic, potential mechanisms, clinical manifestations, diagnosis, management, and prognosis to help clinicians accurately diagnose and treat this malignant tumor.
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http://dx.doi.org/10.3389/fonc.2021.633916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071951PMC
April 2021

MCOLN1/TRPML1 finely controls oncogenic autophagy in cancer by mediating zinc influx.

Autophagy 2021 Apr 23:1-22. Epub 2021 Apr 23.

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.

Macroautophagy/autophagy is elevated to ensure the high demand for nutrients for the growth of cancer cells. Here we demonstrated that MCOLN1/TRPML1 is a pharmaceutical target of oncogenic autophagy in cancers such as pancreatic cancer, breast cancer, gastric cancer, malignant melanoma, and glioma. First, we showed that activating MCOLN1, by increasing expression of the channel or using the MCOLN1 agonists, ML-SA5 or MK6-83, arrests autophagic flux by perturbing fusion between autophagosomes and lysosomes. Second, we demonstrated that MCOLN1 regulates autophagy by mediating the release of zinc from the lysosome to the cytosol. Third, we uncovered that zinc influx through MCOLN1 blocks the interaction between STX17 (syntaxin 17) in the autophagosome and VAMP8 in the lysosome and thereby disrupting the fusion process that is determined by the two SNARE proteins. Furthermore, we demonstrated that zinc influx originating from the extracellular fluid arrests autophagy by the same mechanism as lysosomal zinc, confirming the fundamental function of zinc as a participant in membrane trafficking. Last, we revealed that activating MCOLN1 with the agonists, ML-SA5 or MK6-83, triggers cell death of a number of cancer cells by evoking autophagic arrest and subsequent apoptotic response and cell cycle arrest, with little or no effect observed on normal cells. Consistent with the results, administration of ML-SA5 in Patu 8988 t xenograft mice profoundly suppresses tumor growth and improves survival. These results establish that a lysosomal cation channel, MCOLN1, finely controls oncogenic autophagy in cancer by mediating zinc influx into the cytosol.
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http://dx.doi.org/10.1080/15548627.2021.1917132DOI Listing
April 2021

Proteomic Responses to Alkali Stress in Oats and the Alleviatory Effects of Exogenous Spermine Application.

Front Plant Sci 2021 1;12:627129. Epub 2021 Apr 1.

Institute of Grassland Research of Chinese Academy of Agricultural Sciences, Hohhot, China.

Alkali stress limits plant growth and yield more strongly than salt stress and can lead to the appearance of yellow leaves; however, the reasons remain unclear. In this study, we found that (1) the down-regulation of coproporphyrinogen III oxidase, protoporphyrinogen oxidase, and Pheophorbide a oxygenase in oats under alkali stress contributes to the appearance of yellow leaves (as assessed by proteome and western blot analyses). (2) Some oat proteins that are involved in the antioxidant system, root growth, and jasmonic acid (JA) and indole-3-acetic acid (IAA) synthesis are up-regulated in response to alkalinity and help increase alkali tolerance. (3) We added exogenous spermine to oat plants to improve their alkali tolerance, which resulted in higher chlorophyll contents and plant dry weights than in plants subjected to alkaline stress alone. This was due to up-regulation of chitinase and proteins related to chloroplast structure, root growth, and the antioxidant system. Spermine addition increased sucrose utilization efficiency, and promoted carbohydrate export from leaves to roots to increase energy storage in roots. Spermine addition also increased the IAA and JA contents required for root growth.
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http://dx.doi.org/10.3389/fpls.2021.627129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049610PMC
April 2021

Bisphenol A substitutes and sex hormones in children and adolescents.

Chemosphere 2021 Sep 27;278:130396. Epub 2021 Mar 27.

Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200092, China; School of Public Health, Shanghai Jiao Tong University, Shanghai, 200025, China. Electronic address:

Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as bisphenol A (BPA) substitutes in consumer products. Little is known about the effects of BPA substitutes on reproductive endocrine function in children and adolescents. Thus, we conducted a cross-sectional study to examine the associations of BPA, BPF, and BPS with sex steroid hormones among 6-19-year old participants. Included were 1317 participants with information on BPA, BPF, BPS, and serum sex hormones [total testosterone (TT), estradiol (E), and sex hormone binding globulin (SHBG)]. Multiple linear regression accounting for complex survey design was used to assess the association between bisphenols and sex hormones by sex-age groups. Exposure-response (ER) relationships were examined via restricted cubic splines. Significant association with BPF or BPS was sporadic, but BPA presented inverse association with the free androgen index (FAI, calculated as the ratio of TT to SHBG) and E and positive association with SHBG and TT/E in female adolescents. Further exploration of ER relationships showed that BPA (P for non-linearity = 0.03), BPF (P for non-linearity = 0.005), and BPS (P for non-linearity = 0.08) had a U-shaped relationship with FAI among female adolescents. Additionally, an inverse U-shaped curve was observed for BPA (P for non-linearity = 0.03), BPS (P for non-linearity = 0.01), and BPF (P for non-linearity = 0.01) with SHBG. The associations were virtually nonsignificant among males. Our study demonstrated that BPS and BPF may possess similar endocrine interrupting abilities as BPA.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130396DOI Listing
September 2021

Brain-Targeted Dual Site-Selective Functionalized Poly(β-Amino Esters) Delivery Platform for Nerve Regeneration.

Nano Lett 2021 04 2;21(7):3007-3015. Epub 2021 Apr 2.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, 226001 Nantong, Jiangsu, PR China.

Brain injuries are devastating central nervous system diseases, resulting in cognitive, motor, and sensory dysfunctions. However, clinical therapeutic options are still limited for brain injuries, indicating an urgent need to investigate new therapies. Furthermore, the efficient delivery of therapeutics across the blood-brain barrier (BBB) to the brain is a serious problem. In this study, a facile strategy of dual site-selective functionalized (DSSF) poly(β-amino esters) was developed using bio-orthogonal chemistry for promoting brain nerve regeneration. Fluorescence colocalization studies demonstrated that these proton-sponge DSSF poly(β-amino esters) targeted mitochondria through electrostatic interactions. More importantly, this delivery system could effectively accumulate in the injured brain sites and accelerate the recovery of the injured brain. Finally, this DSSF poly(β-amino esters) platform may provide a new methodology for the construction of dual regioselective carriers in protein/peptide delivery and tissue engineering.
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http://dx.doi.org/10.1021/acs.nanolett.1c00175DOI Listing
April 2021

Antidepressants use and the risk of type 2 diabetes mellitus: A systematic review and meta-analysis.

J Affect Disord 2021 05 13;287:41-53. Epub 2021 Mar 13.

Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Shandong Collaborative Innovation Center for Diagnosis, Treatment & Behavioral Interventions of Mental Disorders, Institute of Mental Health, Jining Medical University, Jining 272013, China; Shandong Key Laboratory of Behavioral Medicine, School of Mental Health, Jining Medical University, Jining 272013, China; Center of Evidence-Based Medicine, Jining Medical University, Jining 272013, China. Electronic address:

Background: This study aimed at examining the effects of different antidepressants on the new onset of T2DM.

Methods: Systematic literature retrieval for cohort and case-control studies was conducted in PubMed, Embase, Web of Science, Cochrane library, Clinical Trials Register of the Cochrane Collaboration and CENTRAL published from January 2000 to October 2020. Pooled estimates were calculated and subgroup analyses were conducted by a fixed or random effects model according to the heterogeneity. Funnel plots and Egger's test were performed to evaluate publication bias. Stata Version 15.1 was used for data analysis.

Results: Thirty studies (24 cohort, 4 nested case-control and 2 case-control studies) were included covering 2,875,567 participants with the follow-up periods from 1 year to 18 years (Median=8.4 years). The pooled estimates of antidepressants use and new-onset T2DM were HR=1.24 (95% CI: 1.18, 1.31), RR=1.42 (95% CI: 0.99, 2.05) and OR=1.17 (95% CI: 1.03, 1.32), respectively. However, subgroup analyses showed that only tricyclic antidepressants (TCAs) use was positively associated with the new onset of T2DM in both cohort studies (combined RR=1.39, 95% CI: 1.17, 1.65) and case-control studies (combined OR=1.25, 95% CI: 1.05, 1.50). Moreover, the risk of T2DM was increased with the duration of antidepressants use in a linear trend (R= 88.51%, P = 0.009).

Limitations: Heterogeneity might impact the results and inference.

Conclusions: Antidepressants use might be a risk factor for the new onset of T2DM. Patients with long-term antidepressants use should be evaluated cautiously for T2DM risk. Routine T2DM screening is necessary in antidepressants users.
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http://dx.doi.org/10.1016/j.jad.2021.03.023DOI Listing
May 2021

Environmental exposure to per- and polyfluoroalkyl substances mixture and male reproductive hormones.

Environ Int 2021 07 18;152:106496. Epub 2021 Mar 18.

Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address:

Background: Previous epidemiological studies on the relationship between per- and polyfluoroalkyl substances (PFAS) exposure and male reproductive hormones were mainly limited to a few legacy PFAS and ignored the possible mixture effects.

Objectives: To assess the associations of PFAS mixture, branched isomers and emerging alternatives of PFAS with male reproductive hormones.

Methods: A total of 902 men (mean age: 31.3 years) were recruited in this cross-sectional study. We quantified 24 targeted PFAS, including 7 branched PFOS isomers, 2 branched PFOA isomers and 2 components of F-53B, in blood plasma. Five reproductive hormones, including total testosterone (TT), estradiol (E), follicular stimulating hormone (FSH), luteinizing hormone (LH) and insulin like factor 3 (INSL3), and sex hormone binding globulin (SHBG) were measured in serum. Associations were first assessed by confounder-adjusted multiple linear regression while correcting for multiple comparisons. Bayesian kernel machine regression (BKMR) and adaptive elastic net (AENET) were further used to assess mixture effects and the adjusted exposure response (ER) relationship of individual PFAS.

Results: After adjusting for confounders, we found that PFAS mixture was significantly and inversely associated with E and E/TT, with perfluoro-n-undecanoic acid (PFuDA) being the major contributor. Although the associations between PFAS mixture and other hormones were non-significant, certain individual PFAS presented significant associations. Notably, perfluoro-n-tridecanoic acid (PFTrDA) and perfluoro-n-dodecanoic acid (PFDoA) were found to be significantly and inversely associated with INSL3, a unique indicator of Leydig cells function. Meanwhile, significant positive associations were found between perfluorobutane sulfonic acid (PFBS) and FSH and between PFuDA and LH. But the associations with branched isomers or F-53B were sporadic and inconsistent.

Conclusions: Our findings provided the evidence that PFAS mixture may reduce E level, and certain PFAS (i.e., PFTrDA and PFDoA) may have negative effects on Leydig cells function among young men. Additional studies are much needed to confirm our results and elucidate potential mechanisms.
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http://dx.doi.org/10.1016/j.envint.2021.106496DOI Listing
July 2021
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