Publications by authors named "Kun Yu"

290 Publications

ILRC: a hybrid biomarker discovery algorithm based on improved L1 regularization and clustering in microarray data.

BMC Bioinformatics 2021 Oct 22;22(1):514. Epub 2021 Oct 22.

Key Laboratory of Intelligent Computing in Medical Image (MIIC), Northeastern University, Ministry of Education, Shenyang, China.

Background: Finding significant genes or proteins from gene chip data for disease diagnosis and drug development is an important task. However, the challenge comes from the curse of the data dimension. It is of great significance to use machine learning methods to find important features from the data and build an accurate classification model.

Results: The proposed method has proved superior to the published advanced hybrid feature selection method and traditional feature selection method on different public microarray data sets. In addition, the biomarkers selected using our method show a match to those provided by the cooperative hospital in a set of clinical cleft lip and palate data.

Method: In this paper, a feature selection algorithm ILRC based on clustering and improved L1 regularization is proposed. The features are firstly clustered, and the redundant features in the sub-clusters are deleted. Then all the remaining features are iteratively evaluated using ILR. The final result is given according to the cumulative weight reordering.

Conclusion: The proposed method can effectively remove redundant features. The algorithm's output has high stability and classification accuracy, which can potentially select potential biomarkers.
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http://dx.doi.org/10.1186/s12859-021-04443-7DOI Listing
October 2021

Recent advances in materials for hemostatic management.

Biomater Sci 2021 Oct 21. Epub 2021 Oct 21.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.

Traumatic hemorrhage can be a fatal event, particularly when large quantities of blood are lost in a short period of time. Therefore, hemostasis has become a crucial part of emergency treatment. For small wounds, hemostasis can be achieved intrinsically depending on the body's own blood coagulation mechanism; however, for large-area wounds, particularly battlefield and complex wounds, materials delivering rapid and effective hemostasis are required. In parallel with the constant progress in science, technology, and society, advances in hemostatic materials have also undergone various iterations by integrating new ideas with old concepts. There are various natural and synthetic hemostatic materials, including hemostatic powders, adhesives, hydrogels, and tourniquets, for the treatment of severe external trauma. This review covers the differences among the currently available hemostatic materials and comprehensively describes the hemostatic effects of different materials based on the underlying mechanisms. Finally, solutions for current issues related to trauma bleeding are discussed, and the prospects of hemostatic materials are proposed.
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http://dx.doi.org/10.1039/d1bm01293bDOI Listing
October 2021

Current Applications of Machine Learning in Spine: From Clinical View.

Global Spine J 2021 Oct 10:21925682211035363. Epub 2021 Oct 10.

Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.

Study Design: Narrative review.

Objectives: This review aims to present current applications of machine learning (ML) in spine domain to clinicians.

Methods: We conducted a comprehensive PubMed search of peer-reviewed articles that were published between 2006 and 2020 using terms (spine, spinal, lumbar, cervical, thoracic, machine learning) to examine ML in spine. Then exclude research of other domain, case report, review or meta-analysis, and which without available abstract or full text.

Results: Total 1738 articles were retrieved from database, and 292 studies were finally included. Key findings of current applications were compiled and summarized in this review. Main clinical applications of those techniques including image processing, diagnosis, decision supporting, operative assistance, rehabilitation, surgery outcomes, complications, hospitalization and cost.

Conclusions: ML had achieved excellent performance and hold immense potential in spine. ML could help clinical staff to improve medical level, enhance work efficiency, and reduce adverse events. However more randomized controlled trials and improvement of interpretability are essential to clinicians accepting models' assistance in real work.
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http://dx.doi.org/10.1177/21925682211035363DOI Listing
October 2021

Critical care ultrasound goal-directed versus early goal-directed therapy in septic shock.

Intensive Care Med 2021 Oct 7. Epub 2021 Oct 7.

Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, 563000, Guizhou, China.

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http://dx.doi.org/10.1007/s00134-021-06538-4DOI Listing
October 2021

Robust Measurement-Driven Cardinality Balance Multi-Target Multi-Bernoulli Filter.

Sensors (Basel) 2021 Aug 25;21(17). Epub 2021 Aug 25.

National Laboratory of Radar Signal Processing, Xidian University, Xi'an 710071, China.

The multi-target tracking filter under the Bayesian framework has strict requirements on the prior information of the target, such as detection probability density, clutter density, and target initial position information. This paper proposes a novel robust measurement-driven cardinality balance multi-target multi-Bernoulli filter (RMD-CBMeMBer) for solving the multiple targets tracking problem when the detection probability density is unknown, the background clutter density is unknown, and the target's prior position information is lacking. In RMD-CBMeMBer filtering, the target state is first extended, so that the extended target state includes detection probability, kernel state, and indicators of target and clutter. Secondly, the detection probability is modeled as a Beta distribution, and the clutter is modeled as a clutter generator that is independent of each other and obeys the Poisson distribution. Then, the detection probability, kernel state, and clutter density are jointly estimated through filtering. In addition, the correlation function (CF) is proposed for creating new Bernoulli component (BC) by using the measurement information at the previous moment. Numerical experiments have verified that the RMD-CBMeMBer filter can solve the multi-target tracking problem under the condition of unknown target detection probability, unknown background clutter density and inadequate prior position information of the target. It can effectively estimate the target detection probability and the clutter density.
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http://dx.doi.org/10.3390/s21175717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434138PMC
August 2021

A comprehensive transcriptomic analysis of alternate interferon signaling pathways in peripheral blood mononuclear cells in rheumatoid arthritis.

Aging (Albany NY) 2021 08 25;13(16):20511-20533. Epub 2021 Aug 25.

Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.

Interferon (IFN) signaling pathways play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Prior studies have mainly studied mixed alterations in the IFN signaling pathway in RA, but these studies have not been sufficient to elucidate how imbalanced IFN signaling subtly influences immune cells. Single-cell RNA (scRNA) sequencing makes it possible to better understand the alternations in the interferon signaling pathways in RA. In the present study, we found that IFN signaling pathways were activated in natural killer (NK) cells, monocytes, T cells, B cells, and most immune cell subclasses in RA. We then explored and analyzed the connections between abnormal IFN signaling pathways and cellular functional changes in RA. Single-Cell rEgulatory Network Inference and Clustering (SCENIC) analysis and gene regulatory network (GRN) construction were also performed to identify key transcription factors in RA. Finally, we also investigated altered IFN signaling pathways in multiple RA peripheral blood samples, which indicated that abnormal IFN signaling pathways were universally observed in RA. Our study contributes to a better understanding of the delicate and precise regulation of IFN signaling in the immune system in RA. Furthermore, common alternations in IFN signaling pathway-related transcription factors could help to identify novel therapeutic targets for RA treatment.
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http://dx.doi.org/10.18632/aging.203432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436925PMC
August 2021

Upregulation of FoxM1 protects against ischemia/reperfusion-induced myocardial injury.

Acta Biochim Pol 2021 Aug 17. Epub 2021 Aug 17.

Department of Cardiology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai 'an, Jiangsu Province, 223300, China.

Background: Ischemia/reperfusion (I/R) induced lethal tissue injury in myocardium. FoxM1 (Forkhead Box M1), expressed in proliferating cardiac progenitor cells, could regulate myocardial development. However, the role of FoxM1 in I/R-induced myocardial injury has not been reported yet.

Methods: Rats were conducted with regional ischemia followed by reperfusion in myocardium through ligation of the left anterior descending coronary artery. Triphenyl-tetrazolium chloride staining was utilized to assess the infarct size. ELISA was performed to detect activities of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Protein expression of FoxM1 in heart tissues and H9c2 were determined by western blot. H9c2 cells were used to establish a hypoxia/reoxygenation cell model, and the cell viability, proliferation and apoptosis were evaluated by MTT, EdU (5-ethynyl-2'-deoxyuridine) staining and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, respectively. Adenovirus (Ad)-mediated over-expression of FoxM1 was injected into the anterior wall of the left ventricle of rats to evaluate the role of FoxM1 on in vivo I/R-induced myocardial injury.

Results: FoxM1 was reduced in heart tissues isolated from rats post myocardial I/R injury. Forced FoxM1 expression increased cell viability and proliferation of hypoxia/reoxygenation-induced H9c2, while repressed the cell apoptosis with increased Bcl-2 and decreased Bax and cleaved caspase-3. Injection of Ad-FoxM1 suppressed infarct size of the heart and decreased activities of CK-MB and LDH.

Conclusion: FoxM1 attenuated I/R-induced myocardial injury, providing potential therapeutic target for the disease.
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http://dx.doi.org/10.18388/abp.2020_5536DOI Listing
August 2021

Follistatin Attenuates Myocardial Fibrosis in Diabetic Cardiomyopathy the TGF-β-Smad3 Pathway.

Front Pharmacol 2021 27;12:683335. Epub 2021 Jul 27.

Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Follistatin (FST) is an endogenous protein that irreversibly inhibits TGF-β superfamily members and plays an anti-fibrotic role in other diseases. However, the role of FST in diabetic cardiomyopathy remains unclear. In this study, we investigated the effects of FST on diabetic cardiomyopathy. The expression of FST was downregulated in the hearts of db/db mice. Remarkably, overexpressing FST efficiently protected against cardiac dysfunction. In addition, overexpression of FST promoted cardiac hypertrophy with an unchanged expression of atrial natriuretic peptide (ANP) and the ratio of myosin heavy chain-β/myosin heavy chain-α (MYH7/MYH6). Furthermore, FST reduced cardiac fibrosis and the production of reactive oxygen species (ROS), and enhanced matrix metallopeptidase 9 (MMP9) activities in db/db mouse hearts. We also observed that overexpressing FST decreased the level of transforming growth factor beta (TGF-β) superfamily members and the phosphorylation of Smad3; consistently, experiments also verified the above results. Our findings revealed the cardioprotective role of FST in attenuating diabetic cardiomyopathy through its anti-fibrotic effects through the TGF-β-Smad3 pathway and provided a promising therapeutic strategy for diabetic cardiomyopathy.
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http://dx.doi.org/10.3389/fphar.2021.683335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353454PMC
July 2021

Effect of Ginsenoside Rh1 on proliferation, apoptosis, and oxidative stress in vascular endothelial cells via regulation of the Nrf2/HO-1 signaling pathway.

J Cardiovasc Pharmacol 2021 Aug 7. Epub 2021 Aug 7.

Department of Cardiology, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian 223300, China.

Abstract: This study aimed to investigate the role of ginsenoside Rh1 in regulating the proliferation, apoptosis, and oxidative stress in oxidized low-density lipoprotein (ox-LDL)-treated human vascular endothelial cells (VECs) and the underlying mechanisms. VECs were treated with ox-LDL to generate an in vitro atherosclerosis model. The effect of ginsenoside Rh1 on cell viability and proliferation was examined by MTT and colony formation assays, respectively, and cell apoptosis was determined by flow cytometry and TUNEL assay. The levels of reactive oxygen species, malondialdehyde, and superoxide dismutase activity were detected using biological assay. Finally, the effect of ginsenoside Rh1 on the levels of BAX and BCL-2, and the Nrf2/HO-1 signaling pathway were determined by qRT-PCR and western blot assays. Treatment with ginsenoside Rh1 significantly increased the proliferation and decreased the apoptosis of ox-LDL-treated VECs in a dose-dependent manner. Moreover, ginsenoside Rh1 also relieved oxidative stress in ox-LDL-treated VECs by activating the Nef2/HO-1 signaling pathway. Thus, ginsenoside Rh1 affects the proliferation, apoptosis, and oxidative stress in ox-LDL-treated VECs by activating the Nef2/HO-1 signaling pathway.
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http://dx.doi.org/10.1097/FJC.0000000000001121DOI Listing
August 2021

Electrical actuation of dielectric droplets by negative liquid dielectrophoresis.

Electrophoresis 2021 Jul 26. Epub 2021 Jul 26.

Department of Instruments Science and Technology, Nanjing University of Science and Technology, Nanjing, P. R. China.

This paper presents an electrical actuation scheme of dielectric droplet by negative liquid dielectrophoresis. A general model of lumped parameter electromechanics for evaluating the electromechanical force acting on the droplets is established. The model reveals the influence of actuation voltage, device geometry, and dielectric parameter on the actuation force for both conductive and dielectric medium. Using this model, we compare the actuation forces for four liquid combinations in the parallel-plate geometry and predict the low voltage actuation of dielectric droplets by negative dielectrophoresis. Parallel experimental results demonstrate such electric actuation of dielectric droplets, including droplet transport, splitting, merging, and dispending. All these dielectric droplet manipulations are achieved at voltages < 100 V . The frequency dependence of droplet actuation velocity in aqueous solution is discussed and the existence of surfactant molecules is believed to play an important role by realigning with the AC electric field. Finally, we present coplanar manipulation of oil and water droplets and formation of oil-in-water emulsion droplet by applying the same low voltage.
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http://dx.doi.org/10.1002/elps.202100093DOI Listing
July 2021

Uniformly-aligned gelatin/polycaprolactone fibers promote proliferation in adipose-derived stem cells and have distinct effects on cardiac cell differentiation.

Int J Clin Exp Pathol 2021 15;14(6):680-692. Epub 2021 Jun 15.

Department of Cardiology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University Jiangsu, China.

Cardiac tissue engineering is a promising technique to regenerate cardiac tissue and treat cardiovascular disease. Here we applied a modified method to generate ultrafine uniformly-aligned composite gelatin/polycaprolactone fibers that mimic functional heart tissue. We tested the physical properties of these fibers and analyzed how these composite fibrous scaffolds affected growth and cardiac lineage differentiation in rat adipose-derived stem cells (rADSCs). We found that uniformly aligned composite fiber scaffolds had an anisotropic arrangement, functional mechanical properties, and strong hydrophilicity. The anisotropic scaffolds improved cell attachment, viability, and proliferative capacity of ADSCs over randomly-aligned scaffolds. Furthermore, uniformly aligned composite fiber scaffolds increased the efficiency of cardiomyogenic differentiation, but might reduce the efficiency of cardiac conduction system cell differentiation in ADSCs compared to randomly-oriented scaffolds and tissue culture polystyrene. However, the randomly-oriented composite scaffolds showed no obviously facilitated effects over tissue culture polystyrene on the two cells' differentiation process. The above results indicate that the scaffold fiber alignment has a greater effect on cell differentiation than the composition of the scaffold. Together, the uniformly-aligned composite fibers displayed excellent physical and biocompatible properties, promoted ADSC proliferation, and played distinct roles in the differentiation of cardiomyogenic cells and cardiac conduction system cells from ADSCs. These results provide new insight for the application of anisotropic fibrous scaffolds in cardiac tissue engineering for both and research.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255201PMC
June 2021

A Pulmonary Artery-Vein Separation Algorithm Based on the Relationship between Subtrees Information.

J Healthc Eng 2021 9;2021:5550379. Epub 2021 Jun 9.

Key Laboratory of Intelligent Computing in Medical Image, Ministry of Education, Shenyang 110189, China.

Physicians need to distinguish between pulmonary arteries and veins when diagnosing diseases such as chronic obstructive pulmonary disease (COPD) and lung tumors. However, manual differentiation is difficult due to various factors such as equipment and body structure. Unlike previous geometric methods of manually selecting the points of seeds and using neural networks for separation, this paper proposes a combined algorithm for pulmonary artery-vein separation based on subtree relationship by implementing a completely new idea and combining global and local information, anatomical knowledge, and two-dimensional region growing method. The algorithm completes the reconstruction of the whole vascular structure and the separation of adhesion points from the tree-like structure characteristics of blood vessels, after which the automatic classification of arteries and veins is achieved by using anatomical knowledge, and the whole process is free from human intervention. After comparing all the experimental results with the gold standard, we obtained an average separation accuracy of 85%, which achieved effective separation. Meanwhile, the time range could be controlled between 40 s and 50 s, indicating that the algorithm has good stability.
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http://dx.doi.org/10.1155/2021/5550379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208852PMC
June 2021

Efficient catalytic combustion of toluene at low temperature by tailoring surficial Pt and interfacial Pt-Al(OH) species.

iScience 2021 Jun 5;24(6):102689. Epub 2021 Jun 5.

International Joint Laboratory of Catalytic Chemistry, State Key Laboratory of Advanced Special Steel, College of Sciences, Shanghai University, Shanghai 200444, China.

Exploring highly efficient and low-cost supported Pt catalysts is attractive for the application of volatile organic compounds (VOCs) combustion. Herein, efficient catalytic combustion of toluene at low temperature over Pt/γ-AlO catalysts has been demonstrated by tailoring active Pt species spatially. Pt/γ-AlO catalyst with low Pt-content (0.26 wt%) containing both interfacial Pt-Al(OH) and surficial metallic Pt (Pt) species exhibited super activity and water-resistant stability for toluene oxidation. The strong metal-support interaction located at the Al-OH-Pt interfaces elongated the Pt-O bond and contributed to the oxidation of toluene. Meanwhile, the OH group at the Al-OH-Pt interfaces had the strongest adsorption and activation capability for toluene and the derived intermediate species were subsequently oxidized by oxygen species activated by surficial Pt to yield carbon dioxide and water. This work initiated an inspiring sight to the design of active Pt species for the VOCs combustion.
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http://dx.doi.org/10.1016/j.isci.2021.102689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233202PMC
June 2021

Weak-emission iridium(III) complexes as fluorescent turn-on probes for ultrasensitive and selective imaging histidine in living cells and rat tissues.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Dec 23;262:120095. Epub 2021 Jun 23.

Department of Chemistry, Wannan Medical College, Wuhu 241002, People's Republic of China. Electronic address:

Visualizing endogenous histidine (His) in living systems is an important and challenging work in life science field. Herein, two weak-emission iridium(III) complexes (IrL1 and IrL2) with solvent ligands (CHCN) were designed and synthesized. It was found that IrL2 showed a better performance for detecting His with more remarkable fluorescence enhancement and lower limit of detection (LOD = 35 nM). Moreover, the recognitionmechanism was confirmed to be a substitution of solvent ligands by His. Importantly, probe IrL2 was applicable to visualize endogenous His in living cells and rat tissue slices via an energy-dependent endocytotic pathway. We hope that this probe can serve as a useful tool for the diagnosis of His-related diseases.
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http://dx.doi.org/10.1016/j.saa.2021.120095DOI Listing
December 2021

Evaluation of genetic diversity and population structure of Fragaria nilgerrensis using EST-SSR markers.

Gene 2021 Sep 25;796-797:145791. Epub 2021 Jun 25.

School of Agriculture, Yunnan University, Kunming 650091, China. Electronic address:

Fragaria nilgerrensis is a diploid wild strawberry widely distributed in Southwest China. Its white color and "peach-like" fragrance of fruits are valuable characters for the genetic improvement of cultivated strawberry plants. Its strong biotic and abiotic resistance and tolerance also enable it to survive in different habitats in the field. In this study, we evaluated the level of genetic variation within and between 16 populations with 169 individuals of F. nilgerrensis using 16 newly developed EST-SSR (expressed sequence tag-simple sequence repeats) markers. The results show that the genetic diversity of this species was high, based on Nei's genetic diversity (0.26) and polymorphic loci (0.41), although it is self-compatible and has clonal propagation. Significant genetic differentiation among populations was also detected by AMOVA analysis (Fst = 0.34), which could be indicative of little gene flow (Nm = 0.43) in F. nilgerrensis. The phylogenetic tree indicates that most of individuals from the same population have clustered together. These populations were not grouped based on the geographical distance, consistent with the Mantel test result (R = 0.0063, P > 0.05). All the populations were assigned into two ancestral groups, with some individuals admixed, suggesting ancestral gene flow had occurred between these two groups. Our developed EST-SSR markers as well as the genetic diversity and population structure analysis of F. nilgerrensis are important for genetic improvement in the breeding process. Moreover, the populations that contain high genetic diversity would be a priority for collection and conservation.
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http://dx.doi.org/10.1016/j.gene.2021.145791DOI Listing
September 2021

Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms.

Leukemia 2021 Jun 25. Epub 2021 Jun 25.

H3 Biomedicine, Cambridge, MA, USA.

We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled patients (42 MDS, 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule I (5 days on/9 days off, range of doses studied 1-40 mg, n = 65) and schedule II (21 days on/7 days off, 7-20 mg, n = 19); 27 patients received treatment for ≥180 days. The most common treatment-related, treatment-emergent adverse events included diarrhea, nausea, fatigue, and vomiting. No complete or partial responses meeting IWG criteria were observed; however, RBC transfusion free intervals >56 days were observed in nine patients who were transfusion dependent at study entry (15%). Of 15 MDS patients with missense SF3B1 mutations, five experienced RBC transfusion independence (TI). Elevated pre-treatment expression of aberrant transcripts of Transmembrane Protein 14C (TMEM14C), an SF3B1 splicing target encoding a mitochondrial porphyrin transporter, was observed in MDS patients experiencing RBC TI. In summary, H3B-8800 treatment was associated with mostly low-grade TAEs and induced RBC TI in a biomarker-defined subset of MDS.
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http://dx.doi.org/10.1038/s41375-021-01328-9DOI Listing
June 2021

Health Protection of CT Radiographers During the Outbreak of COVID-19: Application of Automatic Positioning Technology for Relocatable CT in the Fang Cang Hospital.

Front Med (Lausanne) 2021 4;8:659520. Epub 2021 Jun 4.

Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China.

To investigate the value of automatic positioning technology in improving the protection of radiographers in the relocatable CT room of a Fang Cang hospital during the outbreak of coronavirus disease 2019 (COVID-19). The National Emergency Medical Team of our hospital assumed command of Wuchang Fang Cang Hospital and treated confirmed COVID-19 patients with mild symptoms. Relocatable CT was used to examine patients in this hospital. Automatic positioning technology was applied to avoid close contact between medical staff and patients and to protect medical staff more effectively. Seven hundred lung CT scans acquired from 269 patients were completed from February 17 to 26, 2020 with automatic positioning technology for relocatable CT in a Fang Cang hospital. All scans were conducted successfully using automatic positioning technology. All patients entered the scanning room from a separate door. All the position lines were accurate, and all images met the requirement for diagnosis of COVID-19, with satisfied quality. None of our medical staff had any close contact with patients. Automatic positioning technology applied to relocatable CT can minimize the close contact between technologists and patients and effectively improve the protection of medical staff without sacrificing image quality.
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http://dx.doi.org/10.3389/fmed.2021.659520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212982PMC
June 2021

Expressional diversity of grapevine 3-Hydroxy-3-methylglutaryl-CoA reductase (VvHMGR) in different grapes genotypes.

BMC Plant Biol 2021 Jun 19;21(1):279. Epub 2021 Jun 19.

College of Horticulture, Nanjing Agricultural University, Jiangsu Province, Nanjing City, 210095, PR China.

Background: 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) is a key enzyme in the mevalonate (MVA) pathway, which regulates the metabolism of terpenoids in the cytoplasm and determines the type and content of downstream terpenoid metabolites.

Results: Results showed that grapevine HMGR family has three members, such as VvHMGR1, VvHMGR2, and VvHMGR3. The expression of VvHMGRs in 'Kyoho' has tissue specificity, for example, VvHMGR1 keeps a higher expression, VvHMGR2 is the lowest, and VvHMGR3 gradually decreases as the fruit development. VvHMGR3 is closely related to CsHMGR1 and GmHMGR9 and has collinearity with CsHMGR2 and GmHMGR4. By the prediction of interaction protein, it can interact with HMG-CoA synthase, MVA kinase, FPP/GGPP synthase, diphosphate mevalonate decarboxylase, and participates in the synthesis and metabolism of terpenoids. VvHMGR3 have similar trends in expression with some of the genes of carotenoid biosynthesis and MEP pathways. VvHMGR3 responds to various environmental and phytohormone stimuli, especially salt stress and ultraviolet (UV) treatment. The expression level of VvHMGRs is diverse in grapes of different colors and aroma. VvHMGRs are significantly higher in yellow varieties than that in red varieties, whereas rose-scented varieties showed significantly higher expression than that of strawberry aroma. The expression level is highest in yellow rose-scented varieties, and the lowest in red strawberry scent varieties, especially 'Summer Black' and 'Fujiminori'.

Conclusion: This study confirms the important role of VvHMGR3 in the process of grape fruit coloring and aroma formation, and provided a new idea to explain the loss of grape aroma and poor coloring during production. There may be an additive effect between color and aroma in the HMGR expression aspect.
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http://dx.doi.org/10.1186/s12870-021-03073-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214791PMC
June 2021

PDMS-enhanced slowly degradable Ca-P-Si scaffold: Material characterization, fabrication and in vitro biocompatibility study.

J Appl Biomater Funct Mater 2021 Jan-Dec;19:22808000211023261

College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China.

A slowly degradable bone scaffold can well maintain the balance between new bone regeneration and scaffold resorption, esp. for seniors or patients suffering from pathological diseases, because too fast degradation can lead to the loss of long-term biological stability and result in scaffold failure. In this present study, calcium phosphate silicate (CPS) and polydimethylsiloxane (PDMS) were blended in different ratios to formulate slurries for scaffold fabrication. The effects of crosslinked PDMS on the CPS material properties were first characterized and the most viable formulation of CPS-PDMS slurry was determined based on the aforementioned results to 3D fabricate scaffolds. The biocompatibility of CPS-PDMS was further evaluated based on the scaffold extract's cytotoxicity to osteoblast cells. Furthermore, real-time PCR was used to investigate the effects of scaffold extract to increase osteoblast proliferation. It is showed that the crosslinked PDMS interfered with CPS hydration and reduced both setting rate and compressive strength of CPS. In addition, CPS porosity was also found to increase with PDMS due to uneven water distribution as a result of increased hydrophobicity. Degradation and mineralization studies show that CPS-PDMS scaffold was slowly degradable and induced apatite formation. In addition, the analyses show that the CPS-PDMS scaffold did not exert any cytotoxic effect on osteoblast cells but could improve the cell proliferation via the TGFβ/BMP signaling pathway. In conclusion, CPS-PDMS scaffold is proved to be slowly degradable and biocompatible. Further analyses are therefore needed to demonstrate CPS-PDMS scaffold applications in bone regeneration.
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http://dx.doi.org/10.1177/22808000211023261DOI Listing
October 2021

Magnetic field-mediated Janus particles with sustained driving capability for severe bleeding control in perforating and inflected wounds.

Bioact Mater 2021 Dec 18;6(12):4625-4639. Epub 2021 May 18.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing, 400715, China.

Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge. Therefore, we present a novel hemostatic strategy based on magnetic field-mediated guidance. The biphasic Janus magnetic particle ([email protected]) comprised aggregates of α-FeO nanoparticles (FeO NPs) as the motion actuator, negatively modified microporous starch (MSS) as the base hemostatic substrate, and thrombin as the loaded hemostatic drug. Before application, the particles were first wrapped using NaHCO and then doped with protonated tranexamic acid (TXA-NH ), which ensured their high self-dispersibility in liquids. During application, the particles promptly self-diffused in blood by bubble propulsion and travelled to deep bleeding sites against reverse rushing blood flow under magnetic guidance. tests confirmed the superior hemostatic performance of the particles in perforating and inflected wounds ("V"-shaped femoral artery and "J"-shaped liver bleeding models). The present strategy, for the first time, extends the range of magnetically guided drug carriers to address the challenges in the hemorrhage control of perforating and inflected wounds.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141897PMC
December 2021

Chestnut-like macro-acanthosphere triggered hemostasis: a featured mechanism based on puncturing red blood cells.

Nanoscale 2021 Jun;13(21):9843-9852

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.

Acute hemorrhage that occurs after trauma is a life-threatening condition. Hence, to halt massive bleeding, there is a critical need to develop a suitable therapy. In this study, we developed self-propelling chestnut-like particles (Pro-MAS) comprising a macro-acanthosphere (MAS) coated with calcium carbonate and protonated tranexamic acid to puncture red blood cells (RBCs) and thus activate hemostasis. In vitro assessments revealed that Pro-MAS was biocompatible, biodegradable, and nontoxic; furthermore, it was capable of puncturing RBCs to release procoagulants and activate platelet aggregation for hemostasis. Animal tests showed that self-propelling Pro-MAS effectively traveled through blood flow to the deep ends of wounds; hemorrhage was controlled within 90 s and 4 min in the injured liver and bleeding femoral artery, respectively. Compared with a commercial hemostat, superior hemostasis was achieved with Pro-MAS, which could be ascribed to its functional and structural features. Overall, traveling Pro-MAS possessed sufficient impact force to puncture RBCs and sufficient momentum to reach the targeted bleeding sites. The present study demonstrated the ability of a novel platform, self-propelling MAS particles, to trigger hemostasis by puncturing RBCs. To the best of our knowledge, this is the first trial in which the release of endogenous procoagulants is promoted without the addition of exogenous procoagulants for severe hemorrhage control.
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http://dx.doi.org/10.1039/d1nr01148kDOI Listing
June 2021

Increased Organic Fertilizer and Reduced Chemical Fertilizer Increased Fungal Diversity and the Abundance of Beneficial Fungi on the Grape Berry Surface in Arid Areas.

Front Microbiol 2021 7;12:628503. Epub 2021 May 7.

Department of Horticulture, College of Agriculture, The Key Laboratory of Characteristics of Fruit and Vegetable Cultivation and Utilization of Germoplasm Resources of the Xinjiang Production and Construction Crops, Shihezi University, Shihezi, China.

Fertilizer practices can significantly impact the fruit quality and microbial diversity of the orchards. The fungi on the surface of fruits are essential for fruit storability and safety. However, it is not clear whether fertilization affects the fungal diversity and community structure on the surface of grape berries. Here, grape quality and the fungal diversity on the surface of grapes harvested from three fertilizer treatments were analyzed shortly after grape picking (T0) and following 8 days of storage (T1). The study involved three treatments: (1) common chemical fertilizer for 2 years (CH); (2) increased organic fertilizer and reduced chemical fertilizer for 1 year (A.O); and (3) increased organic fertilizer and reduced chemical fertilizer for 2 years (B.O). The application of increased organic fertilizer and reduced chemical fertilizer increased the soluble solids content (SSC) of the grape berries and decreased the pH of the grape juice. A total of 827,947 high-quality fungal sequences were recovered and assigned to 527 operational taxonomic units. Members of the phylum were dominant in all samples and accounted for 94.41% of the total number of detected sequences, followed by the (5.05%), and unidentified fungi (0.54%). Alpha and beta diversity analyses revealed significantly different fungal populations in the three fertilizer treatments over the two time periods. The fungal diversity and richness on the grape berry surface in the B.O and A.O treatments were higher than those in the CH treatment. Among the detected fungi, the B.O treatments were mainly , , and genera, while the CH treatments were , , and . Moreover, significant differences were revealed between the two assessment times (T0 and T1). The samples from the T0 timepoint had higher fungal richness and diversity than the samples from T1 timepoint. Increasing organic fertilizer usage in grape management could improve grape quality and went on to increase the fungal diversity, as well as the relative abundance (RA) of beneficial fungi on grape berry surfaces. The correlation analysis suggested that the pH of the grape juice was significantly negatively correlated with fungal diversity parameters.
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http://dx.doi.org/10.3389/fmicb.2021.628503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139630PMC
May 2021

LncRNAs induce oxidative stress and spermatogenesis by regulating endoplasmic reticulum genes and pathways.

Aging (Albany NY) 2021 05 6;13(10):13764-13787. Epub 2021 May 6.

Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking University International Hospital, Beijing 102206, China.

Oligozoospermia or low sperm count is a leading cause of male infertility worldwide. Despite decades of work on non-coding RNAs (ncRNAs) as regulators of spermatogenesis, fertilization, and male fertility, the literature on the function of long non-coding RNAs (lncRNAs) in human oligozoospermia is scarce. We integrated lncRNA and mRNA sequencing data from 12 human normozoospermic and oligozoospermic samples and comprehensively analyzed the function of differentially expressed lncRNAs (DE lncRNAs) and mRNAs (DE mRNAs) in male infertility. The target genes of DE lncRNAs were identified using a Gaussian graphical model. Gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were primarily enriched in protein transport and localization to the endoplasmic reticulum (ER). The lncRNA-mRNA co-expression network revealed cis- and trans-regulated target genes of lncRNAs. The transcriptome data implicated DE lncRNAs and DE mRNAs and their target genes in the accumulation of unfolded proteins in sperm ER, PERK-EIF2 pathway-induced ER stress, oxidative stress, and sperm cell apoptosis in individuals with oligozoospermia. These findings suggest that the identified lncRNAs and pathways could serve as effective therapeutic targets for male infertility.
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http://dx.doi.org/10.18632/aging.202971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202879PMC
May 2021

Multi-level height maps-based registration method for sparse LiDAR point clouds in an urban scene.

Appl Opt 2021 May;60(14):4154-4164

The LiDAR sensor has been widely used for reconstruction in urban scenes. However, the current registration method makes it difficult to find stable 3D point correspondences from sparse and low overlapping LiDAR point clouds. In the urban situation, most of the LiDAR point clouds have a common flat ground. Therefore, we propose a novel, to the best of our knowledge, multi-level height (MH) maps-based coarse registration method. It requires that source and target point clouds have a common flat ground, which is easily satisfied for LiDAR point clouds in urban scenes. With MH maps, 3D registration is simplified as 2D registration, increasing the speed of registration. Robust correspondences are extracted in MH maps with different height intervals and statistic height information, improving the registration accuracy. The solid-state LiDAR Livox Mid-100 and mechanical LiDAR Velodyne HDL-64E are used in real-data and dataset experiments, respectively. Verification results demonstrate that our method is stable and outperforms state-of-the-art coarse registration methods for the sparse case. Runtime analysis shows that our method is faster than these methods, for it is non-iterative. Furthermore, our method can be extended for the unordered multi-view point clouds.
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http://dx.doi.org/10.1364/AO.419746DOI Listing
May 2021

Magnetically Guided Nanoworms for Precise Delivery to Enhance In Situ Production of Nitric Oxide to Combat Focal Bacterial Infection In Vivo.

ACS Appl Mater Interfaces 2021 May 11;13(19):22225-22239. Epub 2021 May 11.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.

Overexploitation of antibiotics increases the emergence of multidrug-resistant agents (MDRAs), which may potentially cause a global crisis with severe health consequences. Hence, there is great demand for next-generation antibacterial platforms based on antibiotic-free strategies or targeted therapies to mitigate the emergence of MDRAs. Herein, an all-in-one hollow nanoworm (A-Fe/[email protected]) is developed with a core comprising citrate-capped Au-Ag nanoparticles (Cit-AuAg NPs) loaded with FeO and an l-arginine (L-Arg)-modified polydopamine (PDA) outer shell, possessing exceptional magnetic-targeting ability and a photothermal therapeutic effect. Following intravenous injection, A-Fe/[email protected] can be precisely delivered to the targeted infection sites by an externally applied magnetic field. The in situ produced NO, together with Ag ions and reactive oxygen species, synergistically results in the highly effective elimination of in vivo bacterial infection. With the aid of functional worm-like A-Fe/[email protected] nanocarriers possessing superior biocompatibility, the combination of magnetic guidance therapy and near-infrared-triggered in situ generation of NO may provide a novel approach for eradicating abscesses in the body. To our knowledge, this is the first study highlighting the magnetically guided delivery of worm-like nanocarriers for the antibiotic-free therapy of bacterial infections using in situ generated NO gas, which demonstrates high potential for application in clinical gas therapy.
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http://dx.doi.org/10.1021/acsami.1c04330DOI Listing
May 2021

Dextran hydrogels via disulfide-containing Schiff base formation: Synthesis, stimuli-sensitive degradation and release behaviors.

Carbohydr Polym 2021 Aug 16;265:118085. Epub 2021 Apr 16.

Faculty of Chemical Engineering, Kunming University of Science and Technology, 727 South Jingming Road, Kunming, 650500, China.

Dextran hydrogels (Dex-SS) containing both disulfide and Schiff base bonds were developed via facile method based on the dextran oxidation and subsequent formation of Schiff base linkages between polyaldehyde dextran and cystamine, denoted as the disulfide-containing Schiff base reactions. Results of rheology, swelling and C CP/MAS NMR study indicated that cross-linking degree of Dex-SS hydrogels depended strongly on the molar ratio of -CHO/-NH. Acidic and reductive (GSH) environment sensitive degradation behaviors of Dex-SS hydrogels were then evidenced by SEM, rheology study and Ellman's assay. Moreover, doxorubicin (DOX) was loaded into the hydrogel matrix and pH/GSH-responsive release behaviors were demonstrated. Cytocompatibility of Dex-SS hydrogel and effective cell uptake of released DOX was finally proved by transwell assay with HepG2 cells. Take advantages of the abundance of vicinal hydroxyl on a variety of polysaccharides, the disulfide-containing Schiff base reactions is considered as versatile method to develop stimuli-sensitive hydrogels for local drug delivery.
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http://dx.doi.org/10.1016/j.carbpol.2021.118085DOI Listing
August 2021

Ratiometric fluorescence detection of sulfide ions based on lanthanide coordination polymer using guanosine diphosphate as ligand.

Colloids Surf B Biointerfaces 2021 Aug 28;204:111796. Epub 2021 Apr 28.

Jiangxi Key Laboratory of Industrial Ceramics, College of Materials and Chemical Engineering, Pingxiang University, Pingxiang, 337055, China.

The efficiency of energy transfer from guanine nucleotide to terbium ion (Tb) is affected by the phosphate group significantly. Compared with the biomolecules 5'-GMP (guanosine monophosphate), guanosine diphosphate (GDP) exhibits better sensitize ability to Tb ions luminescence. Assisted with the carboxycoumarin ligand, we synthesized a more stable optical [email protected] polymer with the characteristic emission peaks located on 440 nm and 545 nm in this work. The [email protected] polymer is not only rich in metal binding sites, but also maintains a moderate ionic binding force, which helps metal ions to bind or leave it easily. Experiment result shows that [email protected] polymer has the appropriate binding force for Fe ions, which can be destroyed by sulfur ions (S) as the formation of FeS precipitation. Based on this, [email protected] was designed as the ratio fluorescence probe for sulfur ions detection, where the fluorescence at 545 nm can be selectively quenched by Fe ions, while that at 440 nm was unaffected, in the presence of S ions, the quenched fluorescence can be recovered remarkably. With the increasing S ions from 0.1-45 μM, the ratio of fluorescence intensity at 545 nm to 440 nm (F/F) is linear to S concentration, and the detection limit of S was calculated to be 0.073 μM. Contrast to those fluorescence probes with single wavelength emission, [email protected] displays a comparable sensitivity, the introduced self-adjust wavelength improved the detection accuracy efficiently. The above 98.1 % recovery rates of S ions in the actual water sample demonstrated the practicability of [email protected] fluorescence probe.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111796DOI Listing
August 2021

Highly efficient generation of bacterial leaf blight-resistant and transgene-free rice using a genome editing and multiplexed selection system.

BMC Plant Biol 2021 Apr 24;21(1):197. Epub 2021 Apr 24.

Syngenta Biotechnology (China) Co., Ltd, No.25, Life Science Park Road, Beijing, 102206, China.

Background: Rice leaf blight, which is a devastating disease worldwide, is caused by the bacterium Xanthomonas oryzae pv. oryzae (Xoo). The upregulated by transcription activator-like 1 (UPT) effector box in the promoter region of the rice Xa13 gene plays a key role in Xoo pathogenicity. Mutation of a key bacterial protein-binding site in the UPT box of Xa13 to abolish PXO99-induced Xa13 expression is a way to improve rice resistance to bacteria. Highly efficient generation and selection of transgene-free edited plants are helpful to shorten and simplify the gene editing-based breeding process. Selective elimination of transgenic pollen of T0 plants can enrich the proportion of T1 transgene-free offspring, and expression of a color marker gene in seeds makes the selection of T2 plants very convenient and efficient. In this study, a genome editing and multiplexed selection system was used to generate bacterial leaf blight-resistant and transgene-free rice plants.

Results: We introduced site-specific mutations into the UPT box using CRISPR/Cas12a technology to hamper with transcription-activator-like effector (TAL) protein binding and gene activation and generated genome-edited rice with improved bacterial blight resistance. Transgenic pollen of T0 plants was eliminated by pollen-specific expression of the α-amylase gene Zmaa1, and the proportion of transgene-free plants increased from 25 to 50% among single T-DNA insertion events in the T1 generation. Transgenic seeds were visually identified and discarded by specific aleuronic expression of DsRed, which reduced the cost by 50% and led to up to 98.64% accuracy for the selection of transgene-free edited plants.

Conclusion: We demonstrated that core nucleotide deletion in the UPT box of the Xa13 promoter conferred resistance to rice blight, and selection of transgene-free plants was boosted by introducing multiplexed selection. The combination of genome editing and transgene-free selection is an efficient strategy to accelerate functional genomic research and plant breeding.
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http://dx.doi.org/10.1186/s12870-021-02979-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066475PMC
April 2021

suppresses proliferation and induces apoptosis of colorectal cancer cells by repressing oncogene .

Aging (Albany NY) 2021 04 20;13(8):11665-11677. Epub 2021 Apr 20.

Department of Colorectal Cancer Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.

Colorectal cancer (CRC), a common malignant tumor in the digestive tract, is a leading cause of cancer-related death. has been reported to act as a tumor suppressor gene in various tumors. This study aims to assess the role of SPRY4 in colorectal cancer (CRC) and uncover its underlying mechanisms. Firstly, the expression levels of were measured in CRC cell lines. -overexpressing or silencing plasmids were transfected into CRC cells to regulate its expression level. CCK-8, colony formation, EdU assay, wound-healing and Transwell assays were performed to determine cell proliferation, invasion and migration abilities. Then, apoptosis was measured by flow cytometry analysis, and the expression of apoptosis-related protein was analyzed by western-blotting. Next, the tumorigenesis assay was performed in nude mice. According to the results, there was a lower expression of in CRC cell lines compared with normal cell line, and the overexpression of significantly suppressed cell proliferation, migration and invasion, and promoted apoptosis in SW480 cells. Moreover, the enhanced proliferation, invasion and migration upon silencing was reversed by inhibition. In addition, we found that the overexpression of inhibited tumorigenesis by diminishing the size and weight of the tumors. Our study indicates that might be a potential tumor suppressor gene and prognostic factor for patients with CRC.
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http://dx.doi.org/10.18632/aging.202859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109073PMC
April 2021

Biogenetic Acellular Dermal Matrix Maintaining Rich Interconnected Microchannels for Accelerated Tissue Amendment.

ACS Appl Mater Interfaces 2021 Apr 5;13(14):16048-16061. Epub 2021 Apr 5.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.

Given that many people suffer from extensive skin damage, wound repair has drawn tremendous attention in research. Among the various assistant dressing materials that promote healing, a porcine acellular dermal matrix (PADM), as a skin substitute, can efficiently accelerate healing by promoting cell migration and proliferation. However, a simple, low-cost preparation process remains a challenge facing PADM development, particularly because of the inferior elasticity. To overcome these drawbacks, a CaCl-ethanol-HO solution (ternary solution) combined with an additional enzyme treatment was used to obtain a transparent, porous, and elastic PADM that retained the major extracellular matrix composition of the dermis. Our results indicated that alterations in the fiber organization and secondary structural changes in the collagen occurred after treatment. Furthermore, the wound healing and histological analyses clearly revealed an extremely expedited wound repair process following the application of the biocompatible PADM. In conclusion, this study provides new insights into the development of a transparent PADM with a porous structure and good elasticity that can be used as a skin substitute to accelerate the wound healing process. Moreover, this effective technique could potentially be used to extrapolate other decellularized materials in the future.
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http://dx.doi.org/10.1021/acsami.1c00420DOI Listing
April 2021
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