Publications by authors named "Weiping Wang"

345 Publications

Intravitreal injection of an exosome-associated adeno-associated viral vector enhances retinoschisin 1 gene transduction in the mouse retina.

Hum Gene Ther 2021 Apr 9. Epub 2021 Apr 9.

Henan Provincial People's Hospital, 89632, Zhengzhou, Henan, China;

To investigate whether exosome-associated adeno-associated virus Retinoschisin 1 vector improved the transduction efficiency of RS1 in the mouse retina. pAAV2-RS1-ZsGreen plasmid was constructed by homologous recombination. Exosome-associated adeno-associated virus vectors containing human Retinoschisin 1 (RS1) gene (exo-AAV2-RS1-ZsGreen) were isolated from producer cells' supernatant, and confirmed by transmission electron microscopy, nanoparticle tracking analysis and western blotting. In vitro, HEK-293T cells were transduced with AAV2-RS1-ZsGreen and exo-AAV2-RS1-ZsGreen. In vivo, 1 μl of AAV2-RS1-ZsGreen or 1 μl exo-AAV2-RS1-ZsGreen (2×108 genome copies/μl) was injected intravitreally into the C57BL/6J mouse eyes. PBS was injected as controls. The mRNA and the protein expression in the retina were detected. The results demonstrated exo-AAV2-RS1-ZsGreen possessed lipid bilayers, a saucer-like structures and an average of 120 nm particle size. The expression of RS1 and ZsGreen in exo-AAV2-RS1-ZsGreen group were 7.6 times and 5.7 times that of AAV2-RS1-ZsGreen group in HEK-293T cells, respectively. RS1 protein expression increased by 11.8 times in HEK-293T. Furthermore, Intravitreal injection of exo-AAV significantly increased the transduction efficiency of RS1 than AAV. Exo-AAV may be a powerful gene delivery system for gene therapy of X-link retinoschisis as well as other inherited retina degenerations.
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http://dx.doi.org/10.1089/hum.2020.328DOI Listing
April 2021

The protective effect of hydroxylated fullerene pretreatment on pilocarpine-induced status epilepticus.

Brain Res 2021 Apr 5:147468. Epub 2021 Apr 5.

The Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China. Electronic address:

Status epilepticus (SE) is a neurological emergency. The pathological hallmark of neuronal damage after epileptic seizures could be the chain reaction of oxygen free radicals. Hydroxylated fullerenes (HFs) are novel and effective free radical scavengers, which play an important role in various neurological diseases. However, whether they have a protective effect against epileptic seizures remains elusive. Our study explores the effect of pretreatment with HFs in different doses (0.5, 5, and 10 mg/kg) on SEmodels induced by pilocarpine (PILO). The results suggest that HFs have a protective effect on SE in a dose-dependent manner. HFs significantly reduce the incidence of SE, prolong the latency to SE, reduce the malondialdehyde (MDA) levels, and increase the glutathione (GSH) and superoxide dismutase (SOD) levels. In addition, HFs significantly raise the expression of B-cell lymphoma-2 (Bcl-2) and reduce the expression of Bcl-2-associated X protein (Bax). We found that expressions of nuclear NF-E2-related factor 2 (nNrf2), heme oxygenase-1 (HO-1) and NADPH: quinone oxidoreductase-1 (NQO1) were upregulated 24 h after the onset of SE, but the increase was not enough to combat oxidative stress damage, nor to attenuate lipid peroxidation and apoptosis. The expressions of these proteins in HFs pretreatment groups increased more significantly than those in the epilepsy (EP) group, which effectively reduced lipid peroxidation and apoptosis in the hippocampus. In summary, these findings highlight that HFs pretreatment has a protective effect against PILO-induced SE in rats. It may relieve oxidative stress damage by activating the Nrf2-ARE signaling pathway. It provides evidence that fullerene derivatives may have therapeutic potential for epileptic seizures.
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http://dx.doi.org/10.1016/j.brainres.2021.147468DOI Listing
April 2021

Climate network approach reveals the modes of CO concentration to surface air temperature.

Chaos 2021 Mar;31(3):031104

China State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.

Increasing atmospheric carbon dioxide (CO) is expected to be the main factor of global warming. The relation between CO concentrations and surface air temperature (SAT) has been found related to Rossby waves based on a multi-layer complex network approach. However, the significant relations between CO and SAT occur in the South Hemisphere that is not that much influenced by human activities may offer not enough information to formulate targeted carbon reduction policies. Here, we address it by removing the effects of the Rossby waves to reconstruct CO concentrations and SAT multi-layer complex network. We uncover that the CO concentrations are strongly associated with the surrounding SAT regions. The influential regions of CO on SAT occur over eastern Asia, West Asia, North Africa, the coast of North American, and Western Europe. It is shown that CO over Siberia in phase with the SAT variability in eastern East Asia. Indeed, CO concentration variability is causing effects on the recent warming of SAT in some middle latitude regions. Furthermore, sensitive parameters that CO impacts SAT of top 15 carbon emissions countries have been identified. These countries are significantly responsible for global warming, giving implications for carbon emissions reductions. The methodology and results presented here not only facilitate further research in regions of increased sensitivity to the warming resulting from CO concentrations but also can formulate strategies and countermeasures for carbon emission and carbon reduction.
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http://dx.doi.org/10.1063/5.0040360DOI Listing
March 2021

Phytochrome-interacting factor (PIF) in rapeseed (Brassica napus L.): Genome-wide identification, evolution and expression analyses during abiotic stress, light quality and vernalization.

Int J Biol Macromol 2021 Mar 13;180:14-27. Epub 2021 Mar 13.

Southern Regional Collaborative Innovation Center for Grain and Oil Crops in China, Hunan Agricultural University, Changsha, Hunan 410128, China; Oil Crops Research, Hunan Agricultural University, Changsha, Hunan 410128, China; Hunan Branch of National Oilseed Crops Improvement Center, Changsha, Hunan 410128, China. Electronic address:

Phytochrome-interacting factors (PIFs) are members of basic helix-loop-helix (bHLH) transcription factors and the primary partners of phytochromes (PHY) in light signaling. PIFs interact with the P forms of phytochrome to play an important role in the pathways of response to light and temperature in plants. In this study, 30, 12, and 16 potential PIF genes were identified in Brassica napus, Brassica rapa, Brassica oleracea, respectively, which could be divided into three subgroups. The Br/Bo/BnaPIF genes are intron-rich and similar to the PIF genes in Arabidopsis. However, unlike the AtPIFs that exist in multiple alternative-splicing forms, the majority of Br/Bo/BnaPIF genes have no alternative-splicing forms. A total of 52 Br/Bo/BnaPIF proteins have both the conserved active PHYB binding (APB) and bHLH domains. The Ka/Ks ratio revealed that most BnaPIFs underwent purifying selection. A promoter analysis found that light-related, abscisic acid-related and MYB-binding sites were the most abundant in the promoters of BnaPIFs. BnaPIF genes displayed different spatiotemporal patterns of expression and were regulated by light quality, circadian rhythms, cold, heat, and vernalization. Our results are useful for understanding the biological functions of PIF proteins in rapeseed.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.055DOI Listing
March 2021

Integrated energy saving and position tracking controller for the hydraulic lifting servo system.

ISA Trans 2021 Feb 22. Epub 2021 Feb 22.

School of Mechatronic Engineering, Jiangsu Normal University, Xuzhou 221116, China.

High energy efficiency and tracking accuracy are both vital for hydraulic lifting servo systems. However, the appropriate hardware configuration and its corresponding nonlinear controller is always a problem to be solved. To address this multi-objective task, an integrated energy-saving and position tracking controller is developed. Specifically, to reduce the substantial energy dissipation, a system configuration referring to the structure of the three-position-six-way valve is proposed. To ensure accurate tracking performance, a hybrid observer-based output feedback controller is developed. By doing so, the function of flow regeneration and the property of flow matching are achieved, and the tracking accuracy is guaranteed by using only position signal. To validate the effectiveness of the proposed method, a common Lyapunov function is used to prove the stability of the multi-model system, and case studies are conducted to demonstrate the system performance.
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http://dx.doi.org/10.1016/j.isatra.2021.02.033DOI Listing
February 2021

Claulansine F-Donepezil Hybrids as Anti-Alzheimer's Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities.

Molecules 2021 Feb 28;26(5). Epub 2021 Feb 28.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC) 1.63-4.62 μM). Moreover, ()-3-(8-(-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)--((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide () exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, had stronger free-radical scavenging activity. Molecular docking studies revealed that could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate as a leading structure worthy of further investigation.
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http://dx.doi.org/10.3390/molecules26051303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957565PMC
February 2021

The process of biotransformation can produce insect protein and promote the effective inactivation of heavy metals.

Sci Total Environ 2021 Feb 15;776:145864. Epub 2021 Feb 15.

Institute of Environment, Resource, Soil and Fertilizer, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China. Electronic address:

An experiment was performed to study the inactivation effect of aerobic composting on heavy metals in maggot, pig and chicken manures. After composting, Cu mainly occurred in the oxidizable (OXI) fraction with a percentage distribution above 54%. Zn and Cd mainly existed in the bioavailable factor (BF), which has strong activity, with percentage distributions greater than 88.3% and 82.7%, respectively. Cr and Pb mainly existed in the stable residual (RES) fraction with a percentage distribution of approximately 50%. The aerobic composting process had a clear inactivation effect on heavy metals. For maggot manure compost in particular, the inactivation effects of Cu, Cr, Zn, Cd, and Pb were very good throughout the composting process, and the inactivation effect of Pb reached 54.42%. In addition, the process of biotransformation by housefly maggots promoted the conversion of fulvic acid (FA) to humic acid (HA) in pig manure, and the final increase in HA/FA after maggot manure composting was the largest among the different types of manure and beneficial to the inactivation of heavy metals. Compounds containing -CH and -CH groups were reduced, and aromatic structures were enhanced. Moreover, a maggot yield equivalent to 13.2% of the fresh pig manure was achieved during the process of biotransformation. The correlation analysis results showed that moisture content was an important factor affecting the inactivation rates of heavy metals in the three manure composts. Our results highlight that the process of biotransformation by housefly maggots can promote composting maturity and the inactivation of heavy metals, and produce a large amount of insect protein, yielding beneficial ecological and economic benefits.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145864DOI Listing
February 2021

Chronic Intermittent Hypobaric Hypoxia Restores Hippocampus Function and Rescues Cognitive Impairments in Chronic Epileptic Rats Wnt/β-catenin Signaling.

Front Mol Neurosci 2020 20;13:617143. Epub 2021 Jan 20.

Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Epilepsy is a complex neurological disorder with frequent psychiatric, cognitive, and social comorbidities in addition to recurrent seizures. Cognitive impairment, one of the most common comorbidities, has severe adverse effects on quality of life. Chronic intermittent hypobaric hypoxia (CIHH) has demonstrated neuroprotective efficacy in several neurological disease models. In the present study, we examined the effects of CIHH on cognition and hippocampal function in chronic epileptic rats. CIHH treatment rescued deficits in spatial and object memory, hippocampal neurogenesis, and synaptic plasticity in pilocarpine-treated epileptic rats. The Wnt/β-catenin pathway has been implicated in neural stem cell proliferation and synapse development, and Wnt/β-catenin pathway inhibition effectively blocked the neurogenic effects of CIHH. Our findings indicate that CIHH rescues cognitive deficits in epileptic rats Wnt/β-catenin pathway activation. This study establishes CIHH and Wnt/β-catenin pathway regulators as potential treatments for epilepsy- induced cognitive impairments.
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http://dx.doi.org/10.3389/fnmol.2020.617143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874094PMC
January 2021

QTL Mapping of Heat Tolerance in Cucumber ( L.) at Adult Stage.

Plants (Basel) 2021 Feb 8;10(2). Epub 2021 Feb 8.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Heat stress during cucumber production often leads to sunburn of leaves, growth retardation of stems and roots, fruit malformation, and even plant death, which have a great impact on the fruit quality and yield. However, no studies on the genetic inheritance and quantitative trait locus mapping of heat tolerance in cucumber at the adult stage have been reported yet. In this study, a set of 86 recombinant inbred lines (RILs) derived from "99281" (heat-tolerant) and "931" (heat-sensitive) were used to identify the heat tolerance QTL in summer 2018, 2019, and 2020. Eight-week-old plants were exposed to a natural high temperature environment in the field, and the heat injury index was used to indicate the heat tolerance performance. Genetic analysis showed that the heat tolerance of adult cucumber is quantitatively inherited. One QTL named on chromosome 1 was identified. It was delimited by Indel 3-3 and Indel 1-15 and explained 59.6%, 58.1%, and 40.1% of the phenotypic variation in 2018, 2019, and 2020, respectively. The efficiency of marker HT-1, which is closely linked to the locus, was tested using 62 cucumber germplasm accessions and was found to have an accuracy of 97.8% in heat sensitive plants. The was delimited to a 694.5-kb region, containing 98 genes, nine of which may be involved in heat tolerance. Further sequence analysis showed that there are three single-base substitutions within the coding sequences of . Gene expression analyses suggested that the expression of was significantly higher in "99281" than "931" at 14d, 35d, 42d, and 49d after transplanting. This study provides practically useful markers for heat tolerance breeding in cucumber and provides a basis for further identifying heat tolerant genes.
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http://dx.doi.org/10.3390/plants10020324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915975PMC
February 2021

Percutaneous direct pancreatic duct intervention in management of pancreatic fistulas: a primary treatment or temporizing therapy to prepare for elective surgery.

BMC Gastroenterol 2021 Jan 28;21(1):44. Epub 2021 Jan 28.

Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA.

Background: This study evaluates preliminary results of image-guided percutaneous direct pancreatic duct intervention in the management of pancreatic fistula after surgery or pancreatitis when initially ineligible for surgical or endoscopic therapy.

Methods: Between 2001 and 2018 the medical records of all patients that underwent percutaneous pancreatic duct intervention for radiographically confirmed pancreatic fistula initially ineligible for surgical or endoscopic repair were reviewed for demographics, clinical history, procedure details, adverse events, procedure related imaging and laboratory results, ability to directly catheterized the main pancreatic duct, and whether desired clinical objectives were met.

Results: In 10 of 11patients (6 male and 5 female with mean age 60.5, range 39-89) percutaneous pancreatic duct cannulation was possible. The 10 duct interventions included direct ductal suction drainage in 7, percutaneous duct closure in 3 and stent placement in 1. Pancreatic fistulas closed in 7 of 10, 2 were temporized until elective surgery, and 1 palliated until death from malignancy. The single patient with failed duct cannulation resolved the fistula with prolonged catheter drainage of the peri-pancreatic cavity. There were no major adverse events related to intervention.

Conclusion: In patients with pancreatic fistulas initially ineligible for endoscopic therapy or elective surgery, direct percutaneous pancreatic duct interventions are possible, can achieve improvement without major morbidity or mortality, and can improve and maintain the medical condition of patients in preparation for definitive surgery.
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http://dx.doi.org/10.1186/s12876-021-01620-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844943PMC
January 2021

The deubiquitylase USP9X controls ribosomal stalling.

J Cell Biol 2021 Mar;220(3)

Department of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.

When a ribosome stalls during translation, it runs the risk of collision with a trailing ribosome. Such an encounter leads to the formation of a stable di-ribosome complex, which needs to be resolved by a dedicated machinery. The initial stalling and the subsequent resolution of di-ribosomal complexes requires activity of Makorin and ZNF598 ubiquitin E3 ligases, respectively, through ubiquitylation of the eS10 and uS10 subunits of the ribosome. We have developed a specific small-molecule inhibitor of the deubiquitylase USP9X. Proteomics analysis, following inhibitor treatment of HCT116 cells, confirms previous reports linking USP9X with centrosome-associated protein stability but also reveals a loss of Makorin 2 and ZNF598. We show that USP9X interacts with both these ubiquitin E3 ligases, regulating their abundance through the control of protein stability. In the absence of USP9X or following chemical inhibition of its catalytic activity, levels of Makorins and ZNF598 are diminished, and the ribosomal quality control pathway is impaired.
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http://dx.doi.org/10.1083/jcb.202004211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849821PMC
March 2021

Prognostic Significance of Neutrophil to Lymphocyte Ratio Dynamics in Patients with Hepatocellular Carcinoma Treated with Radioembolization Using Glass Microspheres.

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

Division of Vascular/Interventional Radiology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.

Purpose: To study the prognostic significance of neutrophil and lymphocyte dynamics in patients with hepatocellular carcinoma (HCC) treated with radioembolization.

Methods: A retrospective, single-center review of clinical records and treatment parameters (liver volume treated, administered activity, and radiation dose) in consecutive patients who received radioembolization for HCC was performed between August 20, 2015, and May 24, 2019. Neutrophil and lymphocyte variables associated with overall survival (OS) were determined by Barcelona Clinic Liver Cancer (BCLC) stage and were correlated with radioembolization treatment parameters. Statistical methods included Wilcoxon signed-rank test, univariate, and multivariate Cox regression analysis; receiver operating characteristic analysis; and the Kaplan-Meier method.

Results: One hundred sixty-three patients with a median 67.0 years of age were included for analysis. Eighty-one percent of patients received segmental radioembolization with a median treatment dose of 358 Gray (interquartile range 256-497). The post-treatment lymphocyte count decreased significantly in 94.5 % (p < 0.001) of patients but was not predictive of OS (p = 0.248). The pre-procedure neutrophil to lymphocyte ratio (NLR) was not predictive of OS (p = 0.891), and the 1-month post-procedure NLR was a borderline independent predictor of OS (p = 0.05). The NLR ratio (NLRR = NLR/NLR) (Hazard ratio [HR], 1.31; 95% Cl, 1.04-1.66) and change in NLR (ΔNLR= NLR - NLR) (HR, 1.09; 95% CI, 1.02-1.15) were associated with worse OS in BCLC C patients. NLRR (> 3.17) and ΔNLR (> 3.74) were independent predictors when adjusted for tumor presentation, treatment parameters, and liver function. Volume of liver treated and administered activity positively correlated with NLRR and ΔNLR (p < 0.001).

Conclusion: A decrease in lymphocyte count is common after radioembolization, but of little clinical impact. Neither pre-treatment or post-treatment NLR was a predictor of survival in our study population. NLRR and ΔNLR were independent predictors of survival in BCLC stage C disease and had positive correlations with volume of liver tissue treated and administered activity.
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http://dx.doi.org/10.1007/s00259-020-05186-yDOI Listing
January 2021

Correction to: Managing aquifer recharge with multi-source water to realize sustainable management of groundwater resources in Jinan, China.

Environ Sci Pollut Res Int 2021 Feb;28(6):7598

School of Water Conservancy and Environment, University of Jinan, Jinan, 250022, China.

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http://dx.doi.org/10.1007/s11356-020-11965-9DOI Listing
February 2021

The Protective Effects of VVN001 on LPS-Induced Inflammatory Responses in Human RPE Cells and in a Mouse Model of EIU.

Inflammation 2021 Apr 16;44(2):780-794. Epub 2020 Nov 16.

People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Henan Eye Institute, Henan Eye Hospital, 7# Weiwu Road, Zhengzhou, 450003, China.

To investigate protective effects of VVN001 on lipopolysaccharide (LPS)-induced inflammatory response in human retinal pigment epithelial (RPE) cells and in a mouse model of endotoxin-induced uveitis (EIU), and to explore the underlying mechanisms. Human primary RPE (hRPE) and ARPE-19 cells were pretreated with or without VVN001 for 1 h followed by 10 μg/mL LPS stimulation for 24 h. mRNA, and protein levels of inflammatory cytokines were analyzed with real-time PCR, western blotting, and ELISA. EIU was induced by intravitreal injection of 125 ng LPS in female BALB/c mice. VVN001 eye drops (1%) were locally administrated every 4 h for 24 h after LPS injection. Clinical scores were assessed with a slit lamp. mRNA and protein levels of inflammatory cytokines were investigated simultaneously. Compared with the LPS group, VVN001 pretreatment significantly reduced mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), IL-6, IL-8, TNF-α, IL-1β, IL-18, caspase-1 in hRPE, and ARPE-19 cells. Protein overproduction of ICAM-1, TNF-α, IL-1β, NLRP3, caspase-1 P20, and p-IκBα/IκBα stimulated by LPS was suppressed by VVN001 pretreatment. In vivo, VVN001 significantly reduced the average clinical score from 5.0 to 1.3 in EIU mice. Furthermore, overproduction of ICAM-1, IL-1β, NLRP3, caspase-1 P20, and p-IκBα/IκBα at mRNA and protein levels were remarkably suppressed by VVN001. VVN001 alleviated the inflammatory response induced by LPS both in vitro and in vivo. The effect of anti-inflammation is associated with inhibiting the overproduction of ICAM-1 and blocking the activation of NLRP3 inflammasome and the NF-κB signaling pathway.
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http://dx.doi.org/10.1007/s10753-020-01377-9DOI Listing
April 2021

Covalent organic framework Schiff base network-1-based pipette tip solid phase extraction of sulfonamides from milk and honey.

J Chromatogr A 2020 Dec 2;1634:461665. Epub 2020 Nov 2.

College of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua 321004 China.

In this work, a covalent organic framework Schiff base network-1 (SNW-1), was synthesized based on the Schiff base reaction between terephthalaldehyde and melamine and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and nitrogen adsorption-desorption isotherm analyses. The prepared SNW-1 was employed as pipette tip solid phase extraction adsorbent for the extraction of sulfonamides (SAs) prior to high performance liquid chromatography analysis. The parameters affecting the extraction efficiency, including the salt concentration, sample pH, amount of adsorbent, and types and volume of eluent were investigated in detail. Good linearities were obtained between the peak area and SAs concentration ranging from 5 to 500 ng mL with correlation coefficients (R) higher than 0.9998. The limits of detection and RSDs were lower than 0.25 ng mL and 1.9 %, respectively. The developed method was further applied for the determination of SAs in milk and honey samples with recoveries in the range of 85.8 % - 118.0 % and RSDs less than 9.5 %. The results demonstrate that the SNW-1 shows great potential for the enrichment of trace SAs in complex matrices.
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http://dx.doi.org/10.1016/j.chroma.2020.461665DOI Listing
December 2020

Self-Triggered Consensus of Vehicle Platoon System With Time-Varying Topology.

Front Neurorobot 2020 14;14:53. Epub 2020 Oct 14.

China Information Technology Security Evaluation Center, Beijing, China.

This paper focuses on the consensus problem of a vehicle platoon system with time-varying topology via self-triggered control. Unlike traditional control methods, a more secure event-triggered controller considering the safe distance was designed for the vehicle platoon system. Then, a Lyapunov function was designed to prove the stability of the platoon system. Furthermore, based on the new event-triggered function, a more energy efficient self-triggered control strategy was designed by using the Taylor formula. The new self-triggered control strategy can directly calculate the next trigger according to the state information of the last trigger. It avoids continuous calculation and measurement of vehicles. Finally, the effectiveness of the proposed two self-triggered control strategies were verified by numerical simulation experiments.
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http://dx.doi.org/10.3389/fnbot.2020.00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591777PMC
October 2020

Genome-wide identification and expression analysis of CaM/CML genes in Brassica napus under abiotic stress.

J Plant Physiol 2020 Dec 14;255:153251. Epub 2020 Aug 14.

Southern Regional Collaborative Innovation Center for Grain and Oil Crops in China, Hunan Agricultural University, Changsha, Hunan, 410128, China; Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture and Rural Affairs, Wuhan, 430062, China. Electronic address:

Calmodulin (CaM) and calmodulin-like (CML) proteins are primary calcium (Ca) sensors and are involved in the regulation of plant development and stress responses by converting calcium signals into transcriptional responses, protein phosphorylation, or metabolic changes. However, the characterization and expression profiling of CaM/CML genes in Brassica napus remain limited. The present study reports that 25 BnaCaM and 168 BnaCML genes were identified in B. napus. The phylogenetics, gene structures, gene motifs, gene chromosomal locations, syntenic and Ka/Ks analysis, promoter cis-acting elements, and expression characteristics in various organs and under abiotic stress were evaluated. The phylogenetic results revealed a total of 11 subgroups, including one unique clade of CaMs distinct from CMLs. Most of group I (CaM), II, III, and X members are intron rich, while members from the other seven groups are intron-less. The majority of CaM/CML proteins have four EF-hands. Syntenic analysis showed that 91.3 % orthologous CaM/CML gene pairs between B. rapa and B. oleracea were retained as homologous gene pairs in B. napus. Ka/Ks analysis indicated that the majority of BnaCaM/CML experienced purifying selection. Expression analysis showed that BnaCaMs genes are highly and ubiquitously expressed in all of the organs and tissues examined, while distinct BnaCMLs are expressed specifically in particular organs and tissues. In total, 129 BnaCaM/CML were induced by abiotic stress and phytohormones. BnaCMLs from group IV, VI, VIII, and X were strongly induced by freezing treatment, but were not or just slightly induced by chilling treatment. The present study is the first to analyze the CaM/CML gene family in B. napus, which is useful for understanding the functions of the BnaCaM/CML in modulating plant responses to abiotic stress, especially freezing stress.
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http://dx.doi.org/10.1016/j.jplph.2020.153251DOI Listing
December 2020

Prophylactic Extended-Field Irradiation in Patients With Cervical Cancer: A Literature Review.

Front Oncol 2020 2;10:579410. Epub 2020 Oct 2.

Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Currently, the standard radiation field for locally advanced cervical cancer patients without evidence of para-aortic lymph node (PALN) metastasis is the pelvis. Due to the low accuracy of imaging in the diagnosis of PALN metastasis and the high incidence of PALN failure after pelvic radiotherapy, prophylactic pelvic and para-aortic irradiation, also called extended-field irradiation (EFI), is performed for patients with cervical cancer. In the era of concurrent chemoradiotherapy, randomized controlled trials are limited, and whether patients with cervical cancer can benefit from prophylactic EFI is still controversial. With conformal or intensity-modulated radiation therapy, patients tolerate prophylactic EFI very well. The severe toxicities of prophylactic EFI are not significantly higher than those of pelvic radiotherapy. We recommend delivering prophylactic EFI to cervical cancer patients with common iliac lymph nodes metastasis. Clinical trials are needed to investigate whether patients with ≥3 positive pelvic lymph nodes and FIGO stage IIIB disease can benefit from prophylactic EFI. According to the distribution of PALNs, it is reasonable to use the renal vein as the upper border of the radiation therapy field for patients treated with prophylactic EFI. The clinical target volume expansion of the node from the vessel should be smaller in the right para-caval region than in the left lateral para-aortic region. The right para-caval region above L2 or L3 may be omitted from the PALN target volume to reduce the dose to the duodenum. More clinical trials on prophylactic EFI in cervical cancer are needed.
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http://dx.doi.org/10.3389/fonc.2020.579410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567016PMC
October 2020

Managing aquifer recharge with multi-source water to realize sustainable management of groundwater resources in Jinan, China.

Environ Sci Pollut Res Int 2021 Mar 26;28(9):10872-10888. Epub 2020 Oct 26.

School of Water Conservancy and Environment, University of Jinan, Jinan, 250022, China.

Managed aquifer recharge (MAR) is an important approach to address water security, water quality decline, ground subsidence, and aquifer degradation. In this study, the large-scale recharge experiments were conducted in a natural river with multiple water sources. The MAR with multi-source water was investigated by developing an improved matter-element model under a limited recharged quantity and period in Jinan, China. Results showed that the background levels (BL) of groundwater quality before recharge was relatively good. However, the use of different water sources would cause a significant increase in the content of some groundwater quality indexes, which might further induce deterioration of regional groundwater quality. And the water quality in porous and karst aquifer displayed deteriorating trends during different water source recharge. Additionally, the adverse effects of recharge water sources on regional groundwater quality in turn was South-to-North Water Diversion Project (SN) > Yellow River (YR) > Wohushan Reservoir (WR). Meanwhile, the high-risk indexes in groundwater quality were presented during different water source recharge. Accordingly, relevant suggestions and measures were then put forward to optimize the MAR with multi-source water and explore the high-efficiency and low-risk recharge mode.
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http://dx.doi.org/10.1007/s11356-020-11353-3DOI Listing
March 2021

Interrogation of Folic Acid-Functionalized Nanomedicines: The Regulatory Roles of Plasma Proteins Reexamined.

ACS Nano 2020 11 21;14(11):14779-14789. Epub 2020 Oct 21.

Department of Pharmacology, School of Basic Medical Sciences & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200032, People's Republic of China.

Folic acid (FA) has been extensively exploited to facilitate targeted delivery of nanomedicines by recognizing the folate receptor-α (FR-α) overexpressed in many human cancers. Unfortunately, none have been approved for clinical use yet. Here we reveal that FA functionalization induces heavy natural IgM absorption on the liposomal surface, depriving FA of receptor recognition and accelerating complement activation . FA functionalization does not enhance distribution of liposomes in FR-α-overexpressed tumors in comparison to plain liposomes (without FA), but leads to aggravated capture of liposomes by macrophages in the tumor, liver, and spleen. In addition, FA-functionalized polymeric nanoparticles are also vulnerable to natural IgM absorption. This work highlights the pivotal roles of natural IgM in regulating delivery of FA-functionalized nanomedicines. Due to the prevalent association of immune disorders and varying levels of immunoglobulins with cancer patients, extraordinary cautiousness is urged for clinical translation of FA-enabled targeted delivery systems.
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http://dx.doi.org/10.1021/acsnano.0c02821DOI Listing
November 2020

SFC-MS/MS method for simultaneous determination of nimodipine and 3-n-butylphthalide in beagle plasma: application to pharmacokinetic interaction study.

Bioanalysis 2020 Nov 20;12(21):1509-1519. Epub 2020 Oct 20.

Department of Pharmaceutical Analysis, Wuya College of Innovation, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang 110016, PR China.

Nimodipine and 3-n-butylphthalide are co-administered to treat vascular dementia, but the pharmacokinetic interaction between the two drugs is still unknown. Therefore, a robust, high-throughput and economical supercritical fluid chromatography-ESI-MS/MS method has been initially developed to simultaneously determine nimodipine and 3-n-butylphthalide in beagle plasma, in order to study the safety of co-administration. After a simple protein precipitation procedure, isocratic elution with mobile phase of CO and methanol (containing 0.3% formic acid and 2 mM ammonium acetate) was applied to minimize run time and facilitate sensitive and high-throughput bioanalysis. The method was fully validated according to US FDA Guidance. The validated method was then successfully applied in a pharmacokinetic interaction study. The results indicated there is no significant pharmacokinetic interaction between the two drugs.
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http://dx.doi.org/10.4155/bio-2020-0229DOI Listing
November 2020

Development and validation of a predictive model for the diagnosis of neural antibody-mediated epilepsy/ seizure in patients with new-onset seizure or established epilepsy.

Seizure 2020 Dec 5;83:5-12. Epub 2020 Oct 5.

Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China. Electronic address:

Purpose: Currently, the diagnosis of neural antibody-mediated epilepsy/seizure (NAME/S)relies heavily on neural antibody testing, which is time-consuming, costly and introduces diagnostic delays. A statistical tool to predict the probability of a patient with NAME/S is lacking. We aimed to construct a predictive model to help clinicians expedite the diagnostic process.

Methods: We retrospectively recruited subjects (206 in the development group and 62 in the validation group) with new-onset seizures or established epilepsy suspected to have presented with antibody-mediated seizures between January 2014 and December 2019. We collected data about demographics, medical history, clinical manifestations and follow up. Binary logistic regression was used to select potential predictors for the construction of a predictive model. Five-fold cross and bootstrap validation were applied to avoid overfitting. Concordance index, calibration plots and decision curve analysis were used to assess its performance.

Results: The model, incorporating presence/absence of tumour, psychiatric/cognitive/emotional changes, language disturbances, sensory auras, tonic-clonic seizures, multiple seizure events, hyponatremia and MRI inflammation, was visualized as a nomogram. The crude and adjusted concordance indices were both 0.88 with a cut-off value of 0.62, sensitivity of 83.2 % and specificity of 77.4 %. The slope and intercept of the calibration curve were 0 and 1, respectively. The model also showed good performance in the validation group with a concordance index of 0.82, cut-off value of 0.33, sensitivity of 75.5 % and specificity of 73.1 %. The slope was 0.86 and the intercept was 0.039. Decision curve analysis showed that the model was useful with an optimal threshold probability of >4 % in both groups.

Conclusions: Despite limitations such as sample volume and selection bias in subject enrolment, this model may be used to estimate the individualized probability of having NAME/S, deserving further exploration and validation.
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http://dx.doi.org/10.1016/j.seizure.2020.09.032DOI Listing
December 2020

Radiotherapy for Cervical Cancer in Patients with Systemic Lupus Erythematosus.

Cancer Manag Res 2020 21;12:8675-8683. Epub 2020 Sep 21.

Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.

Objective: To determine the toxicity and efficacy of radiotherapy for cervical cancer in patients with systemic lupus erythematosus (SLE).

Methods: Medical records of patients with SLE who received radiation for cervical cancer from January 2011 to January 2019 were reviewed. For definitive radiotherapy, a dose of 50.4 Gy in 28 fractions was delivered by intensity-modulated radiation therapy (IMRT) combined with high-dose-rate brachytherapy of 28 to 30 Gy in 5 fractions. A dose of 45 to 50.4 Gy in 25-28 fractions was delivered for postoperative radiation. All patients were in remission with or without a low dosage of prednisone or immunosuppressive medication. Survival data were analyzed with the Kaplan-Meier method. The incidence of severe toxicities among patients was compared with the chi-square test or Fisher's exact test.

Results: Twelve patients with SLE were included in this study. Definitive radiotherapy was delivered in 7 patients with FIGO (2009) stage II-III disease. Five patients with FIGO I disease received postoperative radiation. The median follow-up time was 22.1 months. The 3-year overall survival (OS) and 3-year progression-free survival (PFS) were 77.8% and 83.3%, respectively. One patient of definitive radiotherapy and one patient of postoperative radiation died due to distant metastasis of cervical cancer. Grade 3 or higher acute and chronic reactions occurred in 58.3% and 8.3% patients, respectively. Acute grade 3 or higher toxicity correlated with the presence of chemotherapy ( = 0.045).

Conclusion: Modern radiotherapy for cervical cancer was well tolerated in SLE patients with remission and provided a favorable outcome.
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http://dx.doi.org/10.2147/CMAR.S264795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518778PMC
September 2020

Increased ABCC4 Expression Induced by ERRα Leads to Docetaxel Resistance via Efflux of Docetaxel in Prostate Cancer.

Front Oncol 2020 28;10:1474. Epub 2020 Aug 28.

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.

Docetaxel is a major treatment for advanced prostate cancer (PCa); however, its resistance compromises clinical effectiveness. Estrogen receptor-related receptor alpha (ERRα) belongs to an orphan nuclear receptor superfamily and was recently found to be closely involved in cancer. In the present study, we found that ERRα was involved in docetaxel resistance in PCa. Overexpression of ERRα conferred docetaxel resistance in PCa cell lines, and cells with ERRα downregulation were more sensitive to docetaxel. Among the drug resistance-related genes, ABCC4 demonstrated synchronous expression after ERRα manipulation in cells. Moreover, both ERRα and ABCC4 were overexpressed in the docetaxel-resistant cell, which could be reversed by ERRα knockdown. The knockdown of ERRα also reversed the reduced drug accumulation in the docetaxel-resistant cell. We also demonstrated for the first time that ABCC4 was a direct target of ERRα as determined by the CHIP and luciferase assays. Bioinformatics analysis revealed high expression of ERRα and ABCC4 in PCa patients, and a number of potential ERRα/ABCC4 targets were predicted. In conclusion, our study demonstrated a critical role for ERRα in docetaxel resistance by directly targeting ABCC4 and stressed the importance of ERRα as a potential therapeutic target for drug-resistant PCa.
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http://dx.doi.org/10.3389/fonc.2020.01474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493678PMC
August 2020

High-throughput sequencing-based analysis of the composition and diversity of endophytic bacterial community in seeds of upland rice.

Arch Microbiol 2021 Mar 29;203(2):609-620. Epub 2020 Sep 29.

School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China.

Upland rice is an ecotype crop resulting from the long-term domestication and evolution of rice in dry land without a water layer. Generally, the stems and leaves are thick and luxuriant, while the leaves also typically broad and light. The root system is developed with abundant root hair, and the osmotic pressure of the root and cell juice concentration in the leaves is high, while this plant is drought-resistant, heat-resistant, and water absorbent. This study aims to reveal the "core flora" of the endophytes in upland rice seeds by examining their diversity and community structures. It further intends to reveal the impact of the soil environment on the formation of endophyte community structures in upland rice seeds by comparing the environmental soil microorganisms in upland rice habitats. In this study, high-throughput sequencing technology based on the Illumina Hiseq 2500 platform was used to investigate the structure and diversity of endophytic bacterial communities using upland rice varieties collected from different locations and soil samples from unified planting sites as materials. Here, 42 endophytic OTUs were found to coexist in the 14 samples. At the phylum level, the first dominant phyla in all the samples were Proteobacteria (93.81-99.99%). At the genus level, Pantoea (8.77-87.77%), Pseudomonas (1.15-61.58%), Methylobacterium (0.40-4.64%), Sphingomonas (0.26-3.85%), Microbacterium (0.01-4.67%) and Aurantimonas (0.04-4.34%), which represent the core microflora in upland rice seeds, served as the dominant genera that coexisted in all the upland rice seeds tested. This study significant for the isolation, screening, functional evaluation, and re-action of various functional microorganisms in upland rice to improve its agronomic traits. It also provides a specific reference for the interaction between microorganisms and plants.
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http://dx.doi.org/10.1007/s00203-020-02058-9DOI Listing
March 2021

A Red Light-Triggered Drug Release System Based on One-Photon Upconversion-Like Photolysis.

Adv Healthc Mater 2020 11 28;9(21):e2001118. Epub 2020 Sep 28.

Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, P. R. China.

Photoresponsive drug release systems can enhance drug accumulation at the sites where light is applied. Nowadays, the photocleavable groups used in the systems usually require ultraviolet or blue light irradiation, which limits tissue penetration depth and is harmful to normal cells and living bodies. A one-photon upconversion-like photolysis strategy, which can cleave green light-activatable prodrugs with red light at the presence of a red light-excitable photosensitizer in organic solvents, is developed. However, both the prodrug and photosensitizer are hydrophobic and their energy transfer process is sensitive to oxygen molecules. Here, a simple strategy to address these problems by loading the two components in biocompatible and biodegradable polymeric micelles, is presented. The developed low-irradiance red light-triggered drug release system has a size around 40 nm and exhibits good stability in aqueous solutions. The micellar encapsulation protects the photolysis reaction from oxygen quenching in normoxia aqueous solutions. The therapeutic effect of the system enhanced by the redlight irradiation is demonstrated through in vitro and in vivo studies, indicating promising potential in cancer therapy. The study provides the first example and also an important reference for applying one-photon upconversion-like photolysis in biomedical applications.
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http://dx.doi.org/10.1002/adhm.202001118DOI Listing
November 2020

miR‑15a inhibits cell apoptosis and inflammation in a temporal lobe epilepsy model by downregulating GFAP.

Mol Med Rep 2020 Oct 30;22(4):3504-3512. Epub 2020 Jul 30.

Department of Neurology, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China.

Temporal lobe epilepsy (TLE) is a type of epilepsy, which is associated with high morbidity and recurrence rates, and is also difficult to treat. Therefore, it is important to identify novel treatments for TLE. In recent years, with the development of molecular therapies, the regulatory mechanisms and networks of microRNAs (miRNAs/miRs) have become areas of great interest in disease research. The present study aimed to determine a potential novel therapeutic target for the treatment of TLE by identifying differentially expressed miRNAs. The function of miR‑15a was verified in vivo and in vitro by constructing a rat epilepsy model and using hippocampal neurons treated with Mg2+‑free medium, respectively. The mRNA expression levels of miR‑15a, glial fibrillary acidic protein (GFAP), interleukin (IL)‑1β, IL‑6 and tumor necrosis factor α (TNF‑α) were analyzed using reverse transcription‑quantitative PCR. Furthermore, the protein expression levels of GFAP were determined using western blotting. TUNEL and flow cytometry assays were used to detect the levels of cell apoptosis both in vitro and in vivo, respectively. In addition, dual‑luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to determine the relationship between miR‑15a and GFAP. The results of the present study suggested that the expression levels of miR‑15a were downregulated in TLE tissues and epileptic cells. It was also discovered that the upregulated expression levels of miR‑15a significantly inhibited the rate of apoptosis in epileptic cells, in addition to the expression levels of IL‑1β, IL‑6 and TNF‑α in vitro and in vivo. Moreover, the dual‑luciferase reporter and RIP assays results demonstrated that miR‑15a directly targeted GFAP in hippocampal neurons. Rescue experiments indicated that increasing the expression levels of GFAP effectively attenuated the inhibitory effects of the high expression levels of miR‑15a on apoptosis and inflammation. In conclusion, the results of the present study suggested that the upregulation of miR‑15a may inhibit cell apoptosis and inflammation in TLE by targeting GFAP, thus providing a potential therapeutic target for the treatment of TLE.
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http://dx.doi.org/10.3892/mmr.2020.11388DOI Listing
October 2020

Hypoxia-stimulated tumor therapy associated with the inhibition of cancer cell stemness.

Biomaterials 2020 12 10;263:120330. Epub 2020 Sep 10.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China. Electronic address:

Cancer stem cells (CSCs) possess self-renewal and clonal tumor initiation capacities, which lead to drug resistance and tumor recurrence. In this work, a hypoxia-stimulated strategy based on a smart triblock vector was developed to enhance therapeutic efficacy through the inhibition of cancer stemness. The triblock precursor was designed with a fluorescence chromophore for monitoring hypoxia, a methoxy nitro-unit for biorecognition, and a poly(ethylene glycol)-folate for cancer cell targeting. As the degree of hypoxia increases, the vectors were progressively dissociated as indicated by the enhanced fluorescence intensity in hypoxic cells and compacted three-dimensional spheres. Furthermore, the expression of stem cell markers such as CD133 and SOX2 was significantly inhibited, and the serial passaging of CSCs was notably impaired after treating CSCs with the vectors. The inhibition of cancer cell stemness significantly improved the anticancer efficiency in vivo. Moreover, tumor initiation was reduced and the median survival time of xenograft tumor models was prolonged by regulating cell stemness under hypoxia. Overall, this work provides a promising approach to inhibit tumor resistance and recurrence for efficient tumor therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120330DOI Listing
December 2020