Publications by authors named "Yun Chen"

1,637 Publications

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Ternary supramolecular nanocomplexes for superior anticancer efficacy of natural medicines.

Nanoscale 2021 Sep 17;13(35):15085-15099. Epub 2021 Sep 17.

Chongqing Research Center for Pharmaceutical Engineering, School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

The discovery of effective anticancer drug delivery systems and elucidation of the mechanism are enormous challenges. Using two drug administration-approved biomaterials, we constructed a natural medicine (NM)-loaded ternary supramolecular nanocomplex (TSN) suitable for large-scale production. The TSN has a better effect against cancer cells/stem cells than NM with differentially upregulated (27 59) and downregulated (165 66) proteins, respectively. Treatment with the TSN induced apoptosis and G2/M arrest, inhibited cell proliferation, metastasis and invasion, reduced colony/sphere formation, and decreased the frequency of side population cells and CD133CD44ABCG2 cells. These results were revealed by multiple analyses (proteomic analysis, transwell migration and colony/sphere formation assays, biomarker profiling, .). We first reported the proteomic analysis of small lung cancer cells responding to a drug or its nanovesicles. We first conducted a proteomic evaluation of tumor cells responding to a drug supramolecular nanosystem. The supramolecular conformation of the TSN and the interactions of the TSN with albumin were verified by molecular docking experiments. The dominant binding forces in the TSN complexation process were electrostatic interactions, van der Waalsinteractions and bond stretching. The TSN binds to albumin more readily than NM does. The TSN has good absorptive and / kinetic properties. The relative bioavailability of the TSN to EA was 458.39%. The NM-loaded TSN is a supramolecular vesicle that can be produced at an industrial scale for efficient cancer therapy.
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http://dx.doi.org/10.1039/d1nr02791cDOI Listing
September 2021

Facile fabrication of soy protein isolate-functionalized nanofibers with enhanced biocompatibility and hemostatic effect on full-thickness skin injury.

Nanoscale 2021 Sep 16. Epub 2021 Sep 16.

Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Disease, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P. R. China.

Extensive full-thickness skin defect lacks self-healing ability. Tissue engineering wound dressing is considered as the most promising approach to promote wound healing. In this study, a series of biocompatible and hemostatic nanofiber dressings were fabricated. Soy protein isolate (SPI) and poly(L-lactic acid) (PLLA) solutions were mixed in certain proportions for high-voltage electrospinning. The obtained products were coded as SPNF- ( = 100, 80, 60 and 40, corresponding to the weight percentage of PLLA solution). We found that SPNF- ( = 100, 80, 60 and 40) could facilitate the adhesion and spread of L929 cells. In particular, SPNF-80 was capable of promoting fibroblast proliferation and diminishing inflammation. Compared with the neat PLLA film (SPNF-100), the biosafety and hemostatic effect of SPNF-80 got significantly improved. The hemostatic effect of SPNF-80 was comparable with that of a commercial gelatin sponge. wound healing assay demonstrated that SPNF-80 could accelerate the wound healing process by enhancing vascularization, re-epithelization and collagen formation. In conclusion, our results reveal that SPNF- has good biocompatibility and hemostatic effect, and exhibits great application potential in wound healing.
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http://dx.doi.org/10.1039/d1nr03430hDOI Listing
September 2021

A Variant of Is Associated With an Atypical Phenotype of Bohring-Opitz Syndrome: Case Report and Literature Review.

Front Pediatr 2021 30;9:678615. Epub 2021 Aug 30.

Department of Pediatrics, Guizhou Provincial People's Hospital, Guiyang, China.

Bohring-Opitz syndrome (BOS) is a rare genetic disease first reported by Bohring et al. in 1999. With the recent development of exome sequencing (ES), truncating mutations in the additional sex-combs-like 1 () gene have been causally implicated in BOS. Herein, we describe a 7-month-old girl with intrauterine growth restriction, severe pulmonary infection, seizures, and craniofacial abnormalities (microcephaly, micro/retrognathia, hypertelorism, depressed nasal bridge, low-set ears and hypertrichosis) at birth. At a later stage, the patient developed global developmental delay. We performed ES and identified a heterozygous mutation in , namely, c.1210C>T/p.R404. However, this case did not have trigonocephaly, facial hemangioma, prominent eyes, myopia, BOS posture, or brain abnormalities (enlarged subarachnoid spaces, agenesis of the corpus callosum, moderately enlarged cerebral ventricles, or prominent frontal subarachnoid spaces), which are common characteristics in most patients with BOS-harboring mutations. These new data expand the phenotype of BOS driven by and may assist in more accurately delineating the phenotypes caused by variants of this gene.
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http://dx.doi.org/10.3389/fped.2021.678615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435705PMC
August 2021

An engineered IL-2 partial agonist promotes CD8 T cell stemness.

Nature 2021 Sep 15. Epub 2021 Sep 15.

Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Adoptive transfer of antigen-specific T cells represents a major advance in cancer immunotherapy, with robust clinical outcomes in some patients. Both the number of transferred T cells and their differentiation state are critical determinants of effective responses. T cells can be expanded with T cell receptor (TCR)-mediated stimulation and interleukin-2, but this can lead to differentiation into effector T cells and lower therapeutic efficacy, whereas maintenance of a more stem-cell-like state before adoptive transfer is beneficial. Here we show that H9T, an engineered interleukin-2 partial agonist, promotes the expansion of CD8 T cells without driving terminal differentiation. H9T led to altered STAT5 signalling and mediated distinctive downstream transcriptional, epigenetic and metabolic programs. In addition, H9T treatment sustained the expression of T cell transcription factor 1 (TCF-1) and promoted mitochondrial fitness, thereby facilitating the maintenance of a stem-cell-like state. Moreover, TCR-transgenic and chimeric antigen receptor-modified CD8 T cells that were expanded with H9T showed robust anti-tumour activity in vivo in mouse models of melanoma and acute lymphoblastic leukaemia. Thus, engineering cytokine variants with distinctive properties is a promising strategy for creating new molecules with translational potential.
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http://dx.doi.org/10.1038/s41586-021-03861-0DOI Listing
September 2021

Serum 25OHD3 of Obese Mice Is Affected by Liver Injury and Correlates with Testosterone Levels and Sperm Motility.

Obes Facts 2021 Aug 20:1-9. Epub 2021 Aug 20.

Henry Fok College of Biology and Agriculture, Shaoguan University, Shaoguan, China.

Introduction: The concentration of 25-hydroxycholecalciferol (25OHD3) in the serum of obese people is low and often accompanied by symptoms of low fertility. Therefore, vitamin D is recommended as a potential treatment option. However, after clinical trials, it was found that vitamin D cannot effectively increase the concentration of 25OHD3 in the serum of obese people. How obesity causes low 25OHD3 concentration and low fertility is unclear.

Methods: We analyzed the physiological and pathological changes in obese mice induced by a high-fat diet (HFD) and the changes in mice after supplementing with 25OHD3.

Results: The concentration of 25OHD3 in the serum of obese mice induced by HFD was significantly reduced, and these mice showed liver hypertrophy accompanied by abnormal liver injury, testicular hypertrophy, low testosterone levels, high leptin levels, and low sperm motility. The mRNA and protein expression of CYP2R1 of hydroxylated vitamin D3 was significantly reduced; CYP11A1 and CYP11A2, which synthesize testosterone, were significantly reduced. After supplementing with 25OHD3, there was an increase in serum 25OHD3 concentration, testosterone level, and sperm motility, but it cannot improve the degree of obesity, CYP2R1 expression, and liver damage.

Conclusion: Our research shows that there is a metabolic interference mediated by 25OHD3 and testosterone between obesity and low sperm motility. The results of this study can provide a scientific basis for studying the mechanism of 25OHD3 and hormone regulation and treating obese people with low sperm motility.
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http://dx.doi.org/10.1159/000518199DOI Listing
August 2021

Identification of Immune Cell Infiltration Landscape and Their Prognostic Significance in Uveal Melanoma.

Front Cell Dev Biol 2021 26;9:713569. Epub 2021 Aug 26.

Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.

Uveal melanoma (UVM) is the most common primary intraocular cancer in adults. Increasing evidence has demonstrated that immune cell infiltration (ICI) is crucial in predicting patient outcomes and therapeutic efficacy. Thus, describing the immune cell infiltrative landscape of UVM tumors may yield a novel prognostic marker and provide direction for immunotherapeutic selection. In this study, the gene expression data and clinical information of UVM patients were obtained from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. The ICI landscape of UVM was analyzed using the CIBERSORT and ESTIMATE algorithms. Two ICI phenotypes were defined, and the ICI scores were calculated by using principal component analysis algorithms. We found that a subtype with high ICI scores had poorer prognosis and increased expression levels of immune checkpoint-related genes. This study demonstrates that ICI scores are an independent prognostic biomarker and highlights their value in predicting immunotherapeutic outcomes.
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http://dx.doi.org/10.3389/fcell.2021.713569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427429PMC
August 2021

Parametric comparison between sparsity-based and deep learning-based image reconstruction of super-resolution fluorescence microscopy.

Biomed Opt Express 2021 Aug 26;12(8):5246-5260. Epub 2021 Jul 26.

Department of Mechanical Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA.

Sparsity-based and deep learning-based image reconstruction algorithms are two promising approaches to accelerate the image acquisition process for localization-based super-resolution microscopy, by allowing a higher density of fluorescing emitters to be imaged in a single frame. Despite the surging popularity, a comprehensive parametric study guiding the practical applications of sparsity-based and deep learning-based image reconstruction algorithms is yet to be conducted. In this study, we examined the performance of sparsity- and deep learning-based algorithms in reconstructing super-resolution images using simulated fluorescent microscopy images. The simulated images were synthesized with varying levels of sparsity and connectivity. We found the deep learning-based VDSR recovers image faster, with a higher recall rate and localization accuracy. The sparsity-based SPIDER recovers more zero pixels truthfully. We also compared the two algorithms using images acquired from a real super-resolution experiment, yielding results agreeing with the results from the evaluation using simulated images. We concluded that VDSR is preferable when accurate emitter localization is needed while SPIDER is more suitable when evaluation of the number of emitters is critical.
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http://dx.doi.org/10.1364/BOE.427989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407828PMC
August 2021

Nanowire Assisted Mechanotyping of Cellular Metastatic Potential.

Adv Funct Mater 2021 Jul 21;31(30). Epub 2021 May 21.

Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.

Nanotechnology has provided tools for next generation biomedical devices which rely on nanostructure interfaces with living cells. biomimetic structures have enabled observation of cell response to various mechanical and chemical cues, and there is a growing interest in isolating and harnessing the specific cues that three-dimensional microenvironments can provide without the requirement for such culture and the experimental drawbacks associated with it. Here we report a randomly oriented gold coated Si nanowire substrate with patterned hydrophobic-hydrophilic areas for differentiation of isogenic breast cancer cells of varying metastatic potential. When considering synthetic surfaces for the study of cell-nanotopography interfaces, randomly oriented nanowires more closely resemble the isotropic architecture of natural extracellular matrix as compared to currently more widely used vertical nanowire arrays. In the study reported here, we show that primary cancer cells preferably attach to the hydrophilic region of randomly oriented nanowire substrate while secondary cancer cells do not adhere. Using machine learning analysis of fluorescence images, cells were found to spread and elongate on the nanowire substrates as compared to a flat substrate, where they mostly remain round, when neither surface was coated with extracellular matrix (ECM) proteins. Such platforms can not only be used for developing bioassays but also as stepping stones for tissue printing technologies where cells can be selectively patterned at desired locations.
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http://dx.doi.org/10.1002/adfm.202101638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425187PMC
July 2021

Interfacial Laser-Induced Graphene Enabling High-Performance Liquid-Solid Triboelectric Nanogenerator.

Adv Mater 2021 Sep 12:e2104290. Epub 2021 Sep 12.

Faculty of Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong.

Laser-induced graphene (LIG) has emerged as a promising and versatile method for high-throughput graphene patterning; however, its full potential in creating complex structures and devices for practical applications is yet to be explored. In this study, an in-situ growing LIG process that enables to pattern superhydrophobic fluorine-doped graphene on fluorinated ethylene propylene (FEP)-coated polyimide (PI) is demonstrated. This method leverages on distinct spectral responses of FEP and PI during laser excitation to generate the environment preferentially for LIG formation, eliminating the need for multistep processes and specific atmospheres. The structured and water-repellant structures rendered by the spectral-tuned interfacial LIG process are suitable as the electrode for the construction of a flexible droplet-based electricity generator (DEG), which exhibits high power conversion efficiency, generating a peak power density of 47.5 W m from the impact of a water droplet 105 µL from a height of 25 cm. Importantly, the device exhibits superior cyclability and operational stability under high humidity and various pH conditions. The facile process developed can be extended to realize various functional devices.
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http://dx.doi.org/10.1002/adma.202104290DOI Listing
September 2021

Enhanced functional connectivity between habenula and salience network in medication-overuse headache complicating chronic migraine positions it within the addiction disorders: an ICA-based resting-state fMRI study.

J Headache Pain 2021 Sep 9;22(1):107. Epub 2021 Sep 9.

Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, 100853, Beijing, China.

Background: Medication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC).

Methods: RS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation.

Results: Increased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients.

Conclusions: The current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.
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http://dx.doi.org/10.1186/s10194-021-01318-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428097PMC
September 2021

Circulating purification of cutting fluid: an overview.

Int J Adv Manuf Technol 2021 Aug 26:1-36. Epub 2021 Aug 26.

Department of Mechanical Engineering and Advanced Materials Science, Council of Scientific and Industrial Research (CSIR) - Central Leather Research Institute (CLRI), Regional Center for Extension and Development, Jalandhar, ,144021 India.

Cutting fluid has cooling and lubricating properties and is an important part of the field of metal machining. Owing to harmful additives, base oils with poor biodegradability, defects in processing methods, and unreasonable emissions of waste cutting fluids, cutting fluids have serious pollution problems, which pose challenges to global carbon emissions laws and regulations. However, the current research on cutting fluid and its circulating purification technique lacks systematic review papers to provide scientific technical guidance for actual production. In this study, the key scientific issues in the research achievements of eco-friendly cutting fluid and waste fluid treatment are clarified. First, the preparation and mechanism of organic additives are summarized, and the influence of the physical and chemical properties of vegetable base oils on lubricating properties is analyzed. Then, the process characteristics of cutting fluid reduction supply methods are systematically evaluated. Second, the treatment of oil mist and miscellaneous oil, the removal mechanism and approach of microorganisms, and the design principles of integrated recycling equipment are outlined. The conclusion is concluded that the synergistic effect of organic additives, biodegradable vegetable base oils and recycling purification effectively reduces the environmental pollution of cutting fluids. Finally, in view of the limitations of the cutting fluid and its circulating purification technique, the prospects of amino acid additive development, self-adapting jet parameter supply system, matching mechanism between processing conditions and cutting fluid are put forward, which provides the basis and support for the engineering application and development of cutting fluid and its circulating purification.
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http://dx.doi.org/10.1007/s00170-021-07854-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390089PMC
August 2021

Event-Triggered Recursive State Estimation for Stochastic Complex Dynamical Networks Under Hybrid Attacks.

IEEE Trans Neural Netw Learn Syst 2021 Aug 31;PP. Epub 2021 Aug 31.

In this article, the event-based recursive state estimation problem is investigated for a class of stochastic complex dynamical networks under cyberattacks. A hybrid cyberattack model is introduced to take into account both the randomly occurring deception attack and the randomly occurring denial-of-service attack. For the sake of reducing the transmission rate and mitigating the network burden, the event-triggered mechanism is employed under which the measurement output is transmitted to the estimator only when a preset condition is satisfied. An upper bound on the estimation error covariance on each node is first derived through solving two coupled Riccati-like difference equations. Then, the desired estimator gain matrix is recursively acquired that minimizes such an upper bound. Using the stochastic analysis theory, the estimation error is proven to be stochastically bounded with probability 1. Finally, an illustrative example is provided to verify the effectiveness of the developed estimator design method.
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http://dx.doi.org/10.1109/TNNLS.2021.3105409DOI Listing
August 2021

Discovery of potential inhibitors targeting the kinase domain of polynucleotide kinase/phosphatase (PNKP): Homology modeling, virtual screening based on multiple conformations, and molecular dynamics simulation.

Comput Biol Chem 2021 Oct 21;94:107517. Epub 2021 May 21.

School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu, 214122, China. Electronic address:

In recent years, the level of interest has been increased in developing the DNA-repair inhibitors, to enhance the cytotoxic effects in the treatment of cancers. Polynucleotide kinase/phosphatase (PNKP) is a critical human DNA repair enzyme that repairs DNA strand breaks by catalyzing the restoration of 5'-phosphate and 3'-hydroxyl termini that are required for subsequent processing by DNA ligases and polymerases. PNKP is the only protein that repairs the 3'-hydroxyl group and 5'-phosphate group, which depicts PNKP as a potential therapeutic target. Besides, PNKP is the only DNA-repair enzyme that contains the 5'-kinase activity, therefore, targeting this kinase domain would motivate the development of novel PNKP-specific inhibitors. However, there are neither crystal structures of human PNKP nor the kinase inhibitors reported so far. Thus, in this present study, a sequential molecular docking-based virtual screening with multiple PNKP conformations integrating homology modeling, molecular dynamics simulation, and binding free energy calculation was developed to discover novel PNKP kinase inhibitors, and the top-scored molecule was finally submitted to molecular dynamics simulation to reveal the binding mechanism between the inhibitor and PNKP. Taken together, the current study could provide some guidance for the molecular docking based-virtual screening of novel PNKP kinase inhibitors.
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http://dx.doi.org/10.1016/j.compbiolchem.2021.107517DOI Listing
October 2021

The Diagnostic Role of Neurophysiological Tests for Premature Ejaculation: A Prospective Multi-Center Study.

J Urol 2021 Aug 30:101097JU0000000000002198. Epub 2021 Aug 30.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Introduction: Premature ejaculation (PE) is one of the most common male sexual dysfunctions. Local anesthetics (LAs) and dapoxetine are frequently used to treat PE, however, previous studies show variable efficacy. This study aims to determine the efficacy of LAs and dapoxetine using a novel classification based on neurophysiological tests.

Materials And Methods: This multi-center cohort study enrolled adult men (n=568) with an intravaginal ejaculatory latency time (IELT) ≤2 min. Patients were divided into four groups according to the results of neurophysiological tests and assigned different treatments for 12 weeks: (1) Penile sensory hyperexcitability type (Sens): LAs; (2) Penile sympathetic hyperexcitability type (Symp): dapoxetine; (3) Mixed type (Mixed): both LAs and dapoxetine; (4) Normal type (Norm): both LAs and dapoxetine. Self-estimated IELT and patient-reported outcomes (PRO) were recorded.

Results: The total percentage of men achieving IELT>2min and ≥5min after treatment were 82.7% and 76.7%, respectively. For men with abnormal results of neurophysiological tests, 401 (86.6%) had improved IELT >2min after the 12-week treatment course, in which 375 (81.0%) achieved IELT ≥5min. All PRO measures improved in each group after 12 weeks of treatment, with greater improvements among those with abnormal neurophysiological tests.

Conclusion: The efficacy of LAs and dapoxetine increased in PE patients with abnormal results of neurophysiological tests. This novel classification of PE using neurophysiological tests could help guide and improve efficacy of PE therapies.
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http://dx.doi.org/10.1097/JU.0000000000002198DOI Listing
August 2021

Lipidated Methotrexate Microbubbles: A Promising Rheumatoid Arthritis Theranostic Medicine Manipulated via Ultrasonic Irradiation.

J Biomed Nanotechnol 2021 Jul;17(7):1293-1304

Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Institute of Ultrasound Medicine, Shenzhen-PKU-HKUST Medical Center, Shenzhen, 518036, China.

designed lipidated methotrexate was synthesized and self-assembled into microbubbles for targeted rheumatoid arthritis theranostic treatment. Controlled lipidatedmethotrexate delivery was achieved by ultrasound-targetedmicrobubble destruction technique. Methotrexate was dissociated inflammatory microenvironment of synovial cavity, owing to representive low pH and enriched leucocyte esterase. We first manipulated methotrexate controlled release with RAW 264.7 cell line and further verified with rheumatoid arthritis rabbits . Results showed that lipidated methotrexate microbubbles precisely affected infection focus and significantly enhanced rheumatoid arthritis curative effect comparing with dissociative methotrexate. This study indicates that lipidated methotrexate microbubbles might be considered as a promising rheumatoid arthritis theranostics medicine.
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http://dx.doi.org/10.1166/jbn.2021.3105DOI Listing
July 2021

Preparation of Amomum longiligulare polysaccharides 1- PLGA nanoparticle and its immune enhancement ability on RAW264.7 cells.

Int Immunopharmacol 2021 Oct 11;99:108053. Epub 2021 Aug 11.

Institute of Traditional South Chinese Veterinary Pharmacology, College of Animal Science and Technology, Hainan University, Haikou 570228, PR China. Electronic address:

Amomum longiligulare polysaccharides 1 (ALP1) was a glucosan that possessed an immune enhancement ability. However, disadvantages including short biological half-life hindered the application of ALP1. To solve these shortcomings, ALP1 was successfully prepared to nanoparticles (ALPP) with poly (lactic-co-glycolic acid) in the present study. And the optimal preparation conditions were developed by using the response surface method with a Box-Behnken design. The results showed that the encapsulation efficiency of ALPP reached a high level (79.88%) when the volume ratio of the water phase to the organic phase was 1:7, the volume ratio of the primary emulsion to the external water phase was 1:7, and the concentration of F68 was 0.7%. ALPP showed a controlled and sustained release. Meanwhile, the scanning electron microscope results showed that ALPP was a kind of nanoparticles with a diameter of 389.77 nm. In addition, the activating effect of ALPP on macrophages was studied. The results indicated that ALPP showed a better activity on promoting the RAW264.7 cells' activities and polarizing RAW264.7 cells into both M1 type and M2 type macrophages, compared to ALP1.
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http://dx.doi.org/10.1016/j.intimp.2021.108053DOI Listing
October 2021

Characterization of the benign lesions with increased Ga-FAPI-04 uptake in PET/CT.

Ann Nucl Med 2021 Aug 23. Epub 2021 Aug 23.

Department of Nuclear Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China.

Objectives: The objective of the study was to characterize benign lesions showing increased Ga-FAPI-04 uptake on FAPI PET/CT.

Methods: We retrospectively reviewed 182 patients with suspected various cancers who were performed Ga-FAPI-04 PET/CT imaging from August 2020 to December 2020. The diagnoses of the benign lesions were made by the CT findings (CT), other imaging information (OII) (contrast enhance CT, FDG PET, ultrasound, MRI or others), clinical information (CI) (medical history, laboratory examination, symptom, physical sign and follow-up information) or histological biopsy (HB).

Results: A total of 185 primary malignant tumors were detected by FAPI PET/CT with the median SUV of 9.0 (range from 0.97 to 25.71). There were 360 benign lesions with increased FAPI uptake were detected in 146 (146/182, 80.2%) patients with the median SUV of 3.64 (range from 1.39 to 21.56), including inflammatory processes (n = 231, 64.2%), exostosis (n = 54, 15%), hemorrhoid (n = 47, 13.1%), fracture (n = 17, 4.7%), hepatic fibrosis (n = 4, 1.1%), and others (n = 7, 1.9%).

Conclusion: Benign lesions with increased Ga-FAPI-04 uptake are common. The overall SUV of benign lesions is lower than that of malignant tumors, however there is a large overlap of SUV range. Similar to FDG PET, some benign lesions can be easily diagnosed by combining CT findings, special location and clinical data, but there are still some lesions that may be confused with malignant lesions, which need to be paid more attention.

Trail Registration: NIH ClinicalTrials.gov (NCT04499365).
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http://dx.doi.org/10.1007/s12149-021-01673-wDOI Listing
August 2021

Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts.

Front Endocrinol (Lausanne) 2021 6;12:664766. Epub 2021 Aug 6.

Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Preeclampsia is a common obstetric disorder affecting 2-8% of pregnancy worldwide. Fibrosis is an important histological change occurring in preeclamptic placenta, and might depend on the excess deposition of collagen I. However, the role of fibrotic placenta and collagen I in the pathogenesis of preeclampsia remains unclear. Therefore, we analyzed the collagen deposition and the expression of Collagen I in human placenta by Masson staining, Sirius red staining and western blotting. Further, the role of collagen I in preeclampsia pathogenesis was studied in C57BL/6 mice. HTR-8/SVneo cells were used to investigate the mechanisms underlying the effects of collagen I in trophoblasts by transcriptome sequencing and pharmacological agonists. Human preeclamptic placenta exhibited a significantly higher degree of fibrosis in stem villi and terminal villi than normal placenta, and was characterized by collagen I deposition. , a single injection of collagen I on gestational day 0.5 led to an increase in systolic pressure of pregnant mice from gestational days 4.5-17.5, to a decrease in weight and number of embryos, and to enhanced placental collagen I expression and degree of fibrosis compared with control mice. , collagen I attenuated the proliferation and invasion of HTR-8SV/neo cells. This effect could be reversed by treatment with agonists of ERK and β-catenin. Moreover, transcriptome sequencing demonstrated that signaling pathways related to cell proliferation and invasion were significantly downregulated in HTR-8SV/neo cells. Thus, we propose that collagen I induced preeclampsia-like symptoms by suppressing the proliferation and invasion of trophoblasts through inhibition of the ERK phosphorylation and WNT/β-catenin signaling pathways. Our findings could pave the way to the discovery of small-molecule inhibitors for preeclampsia treatment and future studies with larger sample size are required.
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http://dx.doi.org/10.3389/fendo.2021.664766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378400PMC
August 2021

Abnormal Functional Connectivity Between the Left Medial Superior Frontal Gyrus and Amygdala Underlying Abnormal Emotion and Premature Ejaculation: A Resting State fMRI Study.

Front Neurosci 2021 29;15:704920. Epub 2021 Jul 29.

Department of Urology, Jiangsu Provincial People's Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Introduction: Premature ejaculation (PE) is a common sexual dysfunction and is found to be associated with abnormal emotion. The amygdala plays an important role in the processing of emotion. The process of ejaculation is found to be mediated by the frontal-limbic neural circuits. However, the correlations between PE and emotion are still unclear.

Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired in 27 PE patients with stable emotion (SPE), 27 PE patients with abnormal emotion (NPE), and 30 healthy controls (HC). We used rs-fMRI to explore the underlying neural mechanisms in SPE, NPE, and HC by measuring the functional connectivity (FC). Differences of FC values among the three groups were compared when choosing bilateral amygdala as the regions of interest (ROIs). We also explored the correlations between the brain regions showing altered FC values and scores of the premature ejaculation diagnostic tool (PEDT)/Eysenck Personality Inventory about neuroticism (EPQ-N) in the PE group.

Results: When the left amygdala was chosen as the ROI, the SPE group exhibited an increased FC between the left medial superior frontal gyrus (SFGmed) and amygdala compared with the NPE or HC group. When the right amygdala was chosen as the ROI, the NPE group exhibited a decreased FC between the left SFGmed and right amygdala compared with the HC group. In addition, FC values of the left SFGmed had positive correlations with PEDT and negative correlations with EPQ-N scores in the PE group. Moreover, FC values of the left superior temporal gyrus had positive correlations with EPQ-N scores in the PE group.

Conclusion: The increased FC values between the left SFGmed and amygdala could reflect a compensatory cortical control mechanism with the effect of stabilized emotion in the limbic regions of PE patients. Abnormal FC between these brain regions could play a critical role in the physiopathology of PE and could help us in dividing PE into more subtypes.
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http://dx.doi.org/10.3389/fnins.2021.704920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375680PMC
July 2021

Variations in seasonal and inter-annual carbon fluxes in a semi-arid sandy maize cropland ecosystem in China's Horqin Sandy Land.

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

Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, 320 Donggang West Road, Lanzhou, 730000, China.

Sandy cropland ecosystems are major terrestrial ecosystems in semi-arid regions of northern China's Horqin Sandy Land, where they play an important role in the regional carbon balance. Continuous observation of the CO flux was conducted from 2014 to 2018 using the eddy covariance technique in a sandy maize cropland ecosystem in the Horqin Sandy Land. We analyzed carbon fluxes (the net ecosystem exchange (NEE) of CO, ecosystem respiration (R), and the gross primary productivity (GPP) and their responses to environmental factors at different temporal scales using Random Forest models and correlation analysis. We found that the sandy cropland was a carbon sink, with an annual mean NEE of -124.4 g C m yr. However, after accounting for carbon exports and imports, the cropland became a net carbon source, with net biome production ranging from -501.1 to -266.7 g C m yr. At a daily scale, the Random Forest algorithm revealed that photosynthetic photon flux density, soil temperature, and soil moisture were the main drivers for variation of GPP, R, and NEE at different integration periods. At a monthly scale, GPP and R increased with increasing leaf area index (LAI), so the maize ecosystem's carbon sequestration capacity increased with increasing LAI. At an annual scale, water availability (precipitation and irrigation) played a dominant role in explaining inter-annual variability of GPP and R. Affected by climate (e.g., precipitation) and field management (e.g., cultivation, irrigation), carbon fluxes differed greatly between years in the maize system.
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http://dx.doi.org/10.1007/s11356-021-15751-zDOI Listing
August 2021

Analysis of Prevalence, Influencing Factors, and Countermeasures of Short Stature in Children and Adolescents Aged 6∼14 in Furong District, Changsha City, in 2020.

Evid Based Complement Alternat Med 2021 6;2021:3933854. Epub 2021 Aug 6.

Department of Pediatric Orthopedics, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong, China.

In recent years, children's and adolescents' growth and development issues have received increasing attention with the socioeconomic development. The etiology of child short stature involves heredity, race, sex, nutrition, and a variety of endocrine hormones, which is very complex. The age of 6∼14 is the key period of children's development. Understanding the height characteristics, the prevalence of short stature, and its influencing factors at this stage and formulating preventive measures as soon as possible are conducive to improving the average height of children and reducing the incidence of short stature. In this study, cluster sampling was used to select 56,865 children and adolescents aged 6∼14 years old from 40 primary and secondary schools in Furong District of Changsha City, and the height of each child and adolescent was measured. The results showed that the overall crude prevalence of short stature in children aged 6∼14 in Furong District of Changsha is 2.82%. Growth hormone level <10 g/L, pubertal retardation, familial short stature, low egg intake, and intrauterine growth retardation are independent risk factors affecting the occurrence of short stature. In order to improve the status quo of short stature of children aged 6∼14 in Furong District, Changsha City, targeted intervention should be strengthened for people with combined high risk factors.
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http://dx.doi.org/10.1155/2021/3933854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367590PMC
August 2021

Protein acetylation and deacetylation in plant-pathogen interactions.

Environ Microbiol 2021 Aug 16. Epub 2021 Aug 16.

State Key Laboratory of Rice Biology, and Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Protein acetylation and deacetylation catalysed by lysine acetyltransferases (KATs) and deacetylases (KDACs), respectively, are major mechanisms regulating various cellular processes. During the fight between microbial pathogens and host plants, both apply a set of measures, including acetylation interference, to strengthen themselves while suppressing the other. In this review, we first summarize KATs and KDACs in plants and their pathogens. Next, we introduce diverse acetylation and deacetylation mechanisms affecting protein functions, including the regulation of enzyme activity and specificity, protein-protein or protein-DNA interactions, subcellular localization and protein stability. We then focus on the current understanding of acetylation and deacetylation in plant-pathogen interactions. Additionally, we also discuss potential acetylation-related approaches for controlling plant diseases.
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http://dx.doi.org/10.1111/1462-2920.15725DOI Listing
August 2021

High-density lipoprotein in Alzheimer's disease: From potential biomarkers to therapeutics.

J Control Release 2021 Aug 13;338:56-70. Epub 2021 Aug 13.

Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, China; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, Nanjing 210009, China. Electronic address:

The inverse correlation between high-density lipoprotein (HDL) levels in vivo and the risk of Alzheimer's disease (AD) has become an inspiration for HDL-inspired AD therapy, including plain HDL and various intelligent HDL-based drug delivery systems. In this review, we will focus on the two endogenous HDL subtypes in the central nervous system (CNS), apolipoprotein E-based HDL (apoE-HDL) and apolipoprotein A-I-based HDL (apoA-I-HDL), especially their influence on AD pathophysiology to reveal HDL's potential as biomarkers for risk prediction, and summarize the relevant therapeutic mechanisms to propose possible treatment strategies. We will emphasize the latest advances of HDL as therapeutics (plain HDL and HDL-based drug delivery systems) to discuss the potential for AD therapy and review innovative techniques in the preparation of HDL-based nanoplatforms to provide a basis for the rational design and future development of anti-AD drugs.
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http://dx.doi.org/10.1016/j.jconrel.2021.08.018DOI Listing
August 2021

Neural-Network-Based Set-Membership Fault Estimation for 2-D Systems Under Encoding-Decoding Mechanism.

IEEE Trans Neural Netw Learn Syst 2021 Aug 12;PP. Epub 2021 Aug 12.

In this article, the simultaneous state and fault estimation problem is investigated for a class of nonlinear 2-D shift-varying systems, where the sensors and the estimator are connected via a communication network of limited bandwidth. With the purpose of relieving the communication burden and enhancing the transmission security, a new encoding-decoding mechanism is put forward so as to encode the transmitted data with a finite number of bits. The aim of the addressed problem is to develop a neural-network (NN)-based set-membership estimator for jointly estimating the system states and the faults, where the estimation errors are guaranteed to reside within an optimized ellipsoidal set. With the aid of the mathematical induction technique and certain convex optimization approaches, sufficient conditions are derived for the existence of the desired set-membership estimator, and the estimator gains and the NN tuning scalars are then presented in terms of the solutions to a set of optimization problems subject to ellipsoidal constraints. Finally, an illustrative example is given to demonstrate the effectiveness of the proposed estimator design method.
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http://dx.doi.org/10.1109/TNNLS.2021.3102127DOI Listing
August 2021

Do Community Free-Medication Service Policy Improve Patient Medication Adherence? A Cross-Sectional Study of Patients With Severe Mental Disorders in Beijing Community.

Front Public Health 2021 26;9:714374. Epub 2021 Jul 26.

School of Public Health, Capital Medical University, Beijing, China.

Nowadays, mental health problems have become a major concern affecting economic and social development, with severe mental health disorders being the top priority. In 2013, Beijing began to implement the Community Free-Medication Service policy (CFMS). This article aims to evaluate the effect of the policy on medication adherence. In this study, multi-stage sampling was used to select representative patients as samples. Some of the baseline data were obtained by consulting the archives, and information about patient medication adherence measured by Brooks Medication Adherence Scale was obtained through face-to-face interviews. Logistic regression was used to examine the impact of the policy. Policy participation had a significant positive impact on medication adherence (OR = 1.557). The effect of policy participation on medication adherence in the Medication-only mode and Subsidy-only mode were highly significant, but it was not significant in the Mixed mode. This study found that the CFMS in Beijing as an intervention is effective in improving the medication adherence of community patients. However, the impact of the policy is not consistent among service modes. Reinforcement magnitude and frequency should be considered when designing reinforcement interventions.
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http://dx.doi.org/10.3389/fpubh.2021.714374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351906PMC
August 2021

Occurrence and Prevention of Delayed Autonomous Selfing in (Lamiaceae).

Front Plant Sci 2021 26;12:635310. Epub 2021 Jul 26.

Yunnan Key Laboratory for Integrative Conservation of Plant Species With Extremely Small Populations, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.

Delayed autonomous selfing (DAS) provides reproductive assurance under conditions of pollinator and/or pollen-limitation. Few plant species have been investigated to determine if DAS is terminated when a flower is sufficiently pollinated by a pollen vector, thereby saving plant resources for other purposes. We examined this possibility in bumblebee-pollinated . We first showed that DAS resulting in high fruit set (100%) and seed set (>80%) per flower occurred in the absence of insect pollinators by means of style recurvature and was completed in 94% of flowers 72 h after they opened. In contrast, in flowers pollinated immediately after opening, DAS was prevented by corollas dropping away before styles recurve toward the upper thecae. We next showed that hand-pollination of flowers immediately after they opened resulted in high fruit set (100%) and seed set (>80%) when 5-10 pollen grains or more were deposited on their stigmas, whereas fruit set and seed set were reduced to 45.00 and 22.50%, respectively, when pollen loads were reduced to 1-3 pollen grains. Finally, we showed that on average single pollinator visits deposited 26 pollen grains on stigmas of flowers that had just opened, which is more than enough to ensure high fruit and seed set. Our results indicate that flower longevity is highly correlated with the pollinator environment and female fitness of . , with extended flower longevity allowing DAS to occur being advantageous when pollinators are absent, while reduced floral longevity and prevention of DAS being favored when flowers are pollinated by pollinators. Thus, flower longevity in varies so as to optimize reproductive output and resource efforts, and is dependent on the availability and effectiveness of pollinators to pollinate flowers.
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http://dx.doi.org/10.3389/fpls.2021.635310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351595PMC
July 2021

Bimetallic Sulfide SnS/FeS Nanosheets as High-Performance Anode Materials for Sodium-Ion Batteries.

ACS Appl Mater Interfaces 2021 Aug 11;13(33):39248-39256. Epub 2021 Aug 11.

Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Fukuoka 808-0196, Japan.

Transition-metal sulfide SnS has aroused wide concern due to its high capacity and nanosheet structure, making it an attractive choice as the anode material in sodium-ion batteries. However, the large volume expansion and poor conductivity of SnS lead to inferior cycle stability as well as rate performance. In this work, FeS was in situ introduced to synchronously grow with SnS on rGO to prepare a heterojunction bimetallic sulfide nanosheet SnS/FeS/rGO composite. The composition and distinctive structure facilitate the rapid diffusion of Na and improve the charge transfer at the heterogeneous interface, providing sufficient space for volume expansion and improving anode materials' structural stability. SnS/FeS/rGO bimetallic sulfide electrode boasts a capacity of 768.3 mA h g at the current density of 0.1 A g, and 541.2 mA h g at the current density of 1 A g in sodium-ion batteries, which is superior to that of either single metal sulfide SnS or FeS. TDOS calculation further confirms that the binding of FeS/SnS-Na is more stable than FeS and SnS alone. The superior electrochemical performance of the SnS/FeS/rGO composite material makes it a promising candidate for sodium storage.
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http://dx.doi.org/10.1021/acsami.1c08801DOI Listing
August 2021

A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening.

Lab Invest 2021 Aug 10. Epub 2021 Aug 10.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Endometrium-related malignancies including uterine endometrioid carcinoma, ovarian clear cell carcinoma and ovarian endometrioid carcinoma are major types of gynecologic cancer, claiming more than 13,000 women's lives annually in the United States. In vitro cell models that recapitulate "normal" endometrial epithelial cells and their malignant counterparts are critically needed to facilitate the studies of pathogenesis in endometrium-related carcinomas. To achieve this objective, we have established a human endometrial epithelial cell line, hEM3, through immortalization and clonal selection from a primary human endometrium culture. hEM3 exhibits stable growth in vitro without senescence. hEM3 expresses protein markers characteristic of the endometrial epithelium, and they include PAX8, EpCAM, cytokeratin 7/8, and ER. hEM3 does not harbor pathogenic germline mutations in genes involving DNA mismatch repair (MMR) or homologous repair (HR) pathways. Despite its unlimited capacity of in vitro proliferation, hEM3 cells are not transformed, as they are not tumorigenic in immunocompromised mice. The cell line is amenable for gene editing, and we have established several gene-specific knockout clones targeting ARID1A, a tumor suppressor gene involved in the SWI/SNF chromatin remodeling. Drug screening demonstrates that both HDAC inhibitor and PARP inhibitor are effective in targeting cells with ARID1A deletion. Together, our data support the potential of hEM3 as a cell line model for studying the pathobiology of endometrium-related diseases and for developing effective precision therapies.
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http://dx.doi.org/10.1038/s41374-021-00624-3DOI Listing
August 2021

Unraveling the effects of arbuscular mycorrhizal fungi on cadmium uptake and detoxification mechanisms in perennial ryegrass (Lolium perenne).

Sci Total Environ 2021 Jul 22;798:149222. Epub 2021 Jul 22.

School of Life Sciences and Engineering, Southwest University of Science and Technology, Mianyang 621010, China; Joint Research Unit CTFC-AGROTECNIO-CERCA Center, Lleida 25198, Spain; Department of Crop and Forest Sciences, Universitat de Lleida, Lleida 25198, Spain. Electronic address:

Cadmium (Cd) is a major environmental pollutant and one of the most toxic metals in the environment. Arbuscular mycorrhizal fungi (AMF) assisted phytoremediation can be used to remove Cd from polluted soils but the role of AMF, which mediate in Cd accumulation and tolerance, remains poorly understood. Here we inoculated Lolium perenne with two different AMF species (Glomus etunicatum and Glomus mosseae). Mycorrhizal L. perenne and non-mycorrhizal controls were exposed to Cd stress and we tested the effects of AMF mycorrhization on Cd uptake and subsequent tolerance, as well as the underlying mechanisms. Mycorrhizal infection increased root Cd uptake and we observed that net Cd influx was coupled with net Ca influx. The inactivation of Ca transporter channels decreased Cd uptake in non-inoculated roots to a greater extent than in inoculated roots, indicating that AMF activates additional ion transport channels. In consequence, inoculated plants exhibited higher Cd accumulation in both roots and shoots than non-inoculated controls. However, AMF-inoculated plants showed higher chlorophyll concentrations, photosynthesis, and growth under Cd, indicating lower Cd toxicity in AMF-inoculated plants, despite the increase in Cd uptake. We observed that AMF-inoculated favored the isolation of Cd within cell walls and vacuoles, and had higher concentrations of superoxide dismutase activity and glutathione concentration in roots than non-inoculated plants, consequently experiencing less stress upon Cd exposure. Our results highlight the potential and mechanism of AMF for enhancing phytoremediation of L. perenne in heavy metal contaminated environments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149222DOI Listing
July 2021

Hydroxypropyl chitosan/soy isolate protein conduits promote peripheral nerve regeneration.

Tissue Eng Part A 2021 Aug 10. Epub 2021 Aug 10.

Wuhan University School of Basic Medical Sciences, 36841, 115 Donghu Road, Wuchang District, Wuhan, China, Wuhan, China, 430071;

Designing scaffolds, with optimized micro-structure and function for promoting the release of neuro-related factors, is significant in peripheral nerve regeneration. Herein, a series of hydroxypropyl chitosan/soy protein isolate composite sponges (HCSS) were fabricated by a freeze-drying technique. The physicochemical properties of the resultant HCSS were examined by a Fourier infrared spectrometer, X-ray diffractometer, scanning electron microscope, water absorption assay, water retention assay, and compressive strength assay. The results indicated that HCSS exhibited an interconnected porous micro-structure and a high water retention ratio with the increase in SPI content. The biological characterization found that the HCSS-50 containing 50% SPI content profoundly promoted the proliferation of RSC96 cells and the secretion of neuro-related factors without excessive ROS production. In addition, HCSS-50 could significantly promote the expression of neuro-related factors; for example, the expression of TGF-β was 3 times higher than that of the control group. Finally, an optimized HCSS-based conduit was fabricated from HCSS-50 to repair sciatic nerve injury in rats with the combination of BMSCs or BMSC-derived Schwann cells. The results suggested that the constructed HCSS-based conduit accompanying BMSC-derived Schwann cells could effectively promote axonal regeneration and upregulate expression of neuro-related factors such as Krox20, Zeb2, and GAP43. Collectively, a newly engineered nerve conduit system was developed by incorporating HCSS-50 and BMSC-derived Schwann cells, which could be an alternative candidate for peripheral nerve regeneration.
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http://dx.doi.org/10.1089/ten.TEA.2021.0068DOI Listing
August 2021
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