Publications by authors named "Jianwu Dai"

265 Publications

Single-cell analysis reveals dynamic changes of neural cells in developing human spinal cord.

EMBO Rep 2021 Oct 4:e52728. Epub 2021 Oct 4.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

During central nervous system development, neurogenesis and gliogenesis occur in an orderly manner to create precise neural circuitry. However, no systematic dataset of neural lineage development that covers both neurogenesis and gliogenesis for the human spinal cord is available. We here perform single-cell RNA sequencing of human spinal cord cells during embryonic and fetal stages that cover neuron generation as well as astrocytes and oligodendrocyte differentiation. We also map the timeline of sensory neurogenesis and gliogenesis in the spinal cord. We further identify a group of EGFR-expressing transitional glial cells with radial morphology at the onset of gliogenesis, which progressively acquires differentiated glial cell characteristics. These EGFR-expressing transitional glial cells exhibited a unique position-specific feature during spinal cord development. Cell crosstalk analysis using CellPhoneDB indicated that EGFR glial cells can persistently interact with other neural cells during development through Delta-Notch and EGFR signaling. Together, our results reveal stage-specific profiles and dynamics of neural cells during human spinal cord development.
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http://dx.doi.org/10.15252/embr.202152728DOI Listing
October 2021

Facile fabrication of sandwich-like anthocyanin/chitosan/lemongrass essential oil films via 3D printing for intelligent evaluation of pork freshness.

Food Chem 2021 Sep 8;370:131082. Epub 2021 Sep 8.

College of Food Science, Sichuan Agricultural University, Yaan 625014, China. Electronic address:

In this study, chitosan (CH), mulberry anthocyanin (MA), and lemongrass essential oils (LEO) were used as an interlayer using a 3D printer. Further, cassava starch (CS) was used as a protective layer to form indicator films. The indicator films containing LEO showed significant antioxidant and antibacterial properties, and the release rate of LEO increased with a rise in pH. When chilled pork spoiled, the color of the indicator films changed from red to gray-blue, and the RGB values could be automatically analyzed by a smartphone application to determine pork freshness. These films hold implications as easy-to-use indicators of meat freshness, with great potential for monitoring food spoilage, as part of an intelligent packaging system.
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http://dx.doi.org/10.1016/j.foodchem.2021.131082DOI Listing
September 2021

Contralateral Axon Sprouting but Not Ipsilateral Regeneration Is Responsible for Spontaneous Locomotor Recovery Post Spinal Cord Hemisection.

Front Cell Neurosci 2021 26;15:730348. Epub 2021 Aug 26.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

Spinal cord injury (SCI) usually results in permanent functional impairment and is considered a worldwide medical problem. However, both motor and sensory functions can spontaneously recover to varying extents in humans and animals with incomplete SCI. This study observed a significant spontaneous hindlimb locomotor recovery in Sprague-Dawley rats at four weeks after post-right-side spinal cord hemisection at thoracic 8 (T8). To verify whether the above spontaneous recovery derives from the ipsilateral axonal or neuronal regeneration to reconnect the lesion site, we resected either the scar tissue or right side T7 spinal cord at five weeks post-T8 hemisected injury. The results showed that the spontaneously achieved right hindlimb locomotor function had little change after resection. Furthermore, when T7 left hemisection was performed five weeks after the initial injury, the spontaneously achieved right hindlimb locomotor function was dramatically abolished. A similar result could also be observed when T7 transection was performed after the initial hemisection. The results indicated that it might be the contralateral axonal remolding rather than the ipsilateral axonal or neuronal regeneration beyond the lesion site responsible for the spontaneous hindlimb locomotor recovery. The immunostaining analyses and corticospinal tracts (CSTs) tracing results confirmed this hypothesis. We detected no substantial neuronal and CST regeneration throughout the lesion site; however, significantly more CST fibers were observed to sprout from the contralateral side at the lumbar 4 (L4) spinal cord in the hemisection model rats than in intact ones. In conclusion, this study verified that contralateral CST sprouting, but not ipsilateral CST or neuronal regeneration, is primarily responsible for the spontaneous locomotor recovery in hemisection SCI rats.
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http://dx.doi.org/10.3389/fncel.2021.730348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426601PMC
August 2021

Recent advances in cyclodextrin-based films for food packaging.

Food Chem 2021 Sep 1;370:131026. Epub 2021 Sep 1.

Collegeof Food Science, Sichuan Agricultural University, Ya'an 625014, China. Electronic address:

Cyclodextrins are garnering increasing attention because they offer several benefits. For instance, cyclodextrins can form several complexes and supramolecular structures not only for food packaging but also for applications in other fields of science. In this review, we discussed the physical and chemical properties of cyclodextrins and the mechanism of their inclusion complex formation. The use of cyclodextrins in various types of food packaging is elaborated upon. We also explain the effects of cyclodextrins on the packaging of fruits, vegetables, meat, fish, and processed foods. Furthermore, some feasible suggestions for future applications are provided. In addition to the positive attributes of cyclodextrins, there are some limitations and drawbacks, which are discussed briefly in this review. In summary, this review can serve as a guide for researchers exploring cyclodextrins for the development of various packaging films.
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http://dx.doi.org/10.1016/j.foodchem.2021.131026DOI Listing
September 2021

Long-term stability, high strength, and 3D printable alginate hydrogel for cartilage tissue engineering application.

Biomed Mater 2021 09 28;16(6). Epub 2021 Sep 28.

Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, People's Republic of China.

Cartilage damage is one of the main causes of disability, and 3D bioprinting technology can produce complex structures that are particularly suitable for constructing a customized and irregular tissue engineering scaffold for cartilage repair. Alginate is an attractive biomaterial for bioinks because of its good biological safety profile and fast ionic gelation. However, ionically crosslinked alginate hydrogels are recognized as lacking enough mechanical property and long-term stability due to ion exchange. Here, we developed a double crosslinked alginate (DC-Alg) hydrogel for 3D bioprinting, and human umbilical cord mesenchymal stem cells (huMSCs) could differentiate into chondrocytes on its printed 3D scaffold after 4 weeks' culture. We performed sequential modification of alginate with L-cysteine and 5-norbornene-2-methylamine, and the DC-Alg hydrogels were obtained in the presence of CaCland ultraviolet light with stronger mechanical properties than those of the single ionic crosslinked alginate hydrogels, which was similar to natural cartilage. They also had better stability and could be maintained in DMEM medium for over 1 month, as well good viability for huMSCs. Moreover, the DC-Alg as 3D printing inks demonstrated a better printing accuracy (∼200 µm). After 4 weeks culture of huMSCs in the 3D printed DC-Alg scaffolds, the expressions of chondrogenic genes such as99) were obviously observed, indicating the differentiation of huMSCs into cartilage. Immumohistochemical staining analysis further exhibited cartilage tissue developed well in the 3D printed scaffolds. Our study is the first demonstration of DC-Alg in 3D printing for MSC differentiation into cartilage, which shows a potential application in cartilage defect repair.
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http://dx.doi.org/10.1088/1748-605X/ac2595DOI Listing
September 2021

Characterization and preliminary safety evaluation of nano-SiO isolated from instant coffee.

Ecotoxicol Environ Saf 2021 Aug 25;224:112694. Epub 2021 Aug 25.

Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA; Department of Healthcare and Biomedical Engineering, Chonnam National University(,) Yeosu 59626, South Korea. Electronic address:

The physiological and toxicological evaluation of nano-silicon dioxide (nano-SiO) particles in food is important for ensuring food safety. In this study, nano-SiO particles isolated from five brands of instant coffee, were structurally characterized using transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, dynamic light scattering, and zeta potential analyses. Their toxicity was assessed by measuring cell viability, membrane integrity, and reactive oxygen species (ROS) levels in model gastrointestinal cells (GES-1 and Caco-2). Additionally, mortality, deformity rate, heart rate and death of whole zebra fish embryos were measured. The five types of nano-SiO samples comprised amorphous particles with a purity of approximately 99%, which met the food additive standard. Considering that the original particle size ranged from 10 to 50 nm, the samples were classified as nano-SiO food additives. Nano-SiO did not significantly impact the activity of GES-1 or Caco-2 cells, and no significant cell membrane damage was observed (Caco-2 cells exhibited mild micro damage); however, a slight increase in intracellular RPS levels was detected. Moreover, nano-SiO was found to cause head deformity, pericardial edema, yolk sac edema and tail bending. Collectively, the results show that nano-SiO time- and dose-dependently affects GES-1 and Caco-2 cell viability, as well as the mortality, heart rate, and abnormality rate of zebra fish embryos. Specifically, a high concentration (≥ 200 μg/mL) and long exposure time (≥ 48 h) of food additive nano-SiO affected GES-1, Caco-2 cells, and the gastrointestinal tract in zebra fish embryos.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112694DOI Listing
August 2021

Long-term clinical observation of patients with acute and chronic complete spinal cord injury after transplantation of NeuroRegen scaffold.

Sci China Life Sci 2021 Aug 16. Epub 2021 Aug 16.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, China.

Spinal cord injury (SCI) often results in an inhibitory environment at the injury site. In our previous studies, transplantation of a scaffold combined with stem cells was proven to induce neural regeneration in animal models of complete SCI. Based on these preclinical studies, collagen scaffolds loaded with the patients' own bone marrow mononuclear cells or human umbilical cord mesenchymal stem cells were transplanted into SCI patients. Fifteen patients with acute complete SCI and 51 patients with chronic complete SCI were enrolled and followed up for 2 to 5 years. No serious adverse events related to functional scaffold transplantation were observed. Among the patients with acute SCI, five patients achieved expansion of their sensory positions and six patients recovered sensation in the bowel or bladder. Additionally, four patients regained voluntary walking ability accompanied by reconnection of neural signal transduction. Among patients with chronic SCI, 16 patients achieved expansion of their sensation level and 30 patients experienced enhanced reflexive defecation sensation or increased skin sweating below the injury site. Nearly half of the patients with chronic cervical SCI developed enhanced finger activity. These long-term follow-up results suggest that functional scaffold transplantation may represent a feasible treatment for patients with complete SCI.
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http://dx.doi.org/10.1007/s11427-021-1985-5DOI Listing
August 2021

Recent advances in the fabrication of pH-sensitive indicators films and their application for food quality evaluation.

Crit Rev Food Sci Nutr 2021 Aug 12:1-17. Epub 2021 Aug 12.

College of Food Science, Sichuan Agricultural University, Ya'an, China.

Over a few decades, anthocyanin (ACN)-based colorimetric indicators in intelligent packaging systems have been widely used to monitor the freshness or spoilage of perishable food products. Most of the perishable food products are highly susceptible to enzymatic/microbial spoilage and produce several volatile or nonvolatile organic acid and nitrogenous compounds. As a result, the natural pH of fresh foods significantly changes. Fabrication of CAN-based colorimetric indicators in intelligent packaging systems is an advanced technique that monitors the freshness or spoilage of perishable foods based on the display of color variations at varying pH values. This study focuses on the advancement of pH-sensitive indicators and extraction of colorimetric indicators from commercially available natural sources. Moreover, the fabrication techniques and widespread industrial applications of such indicators have also been discussed. In addition, readers will get information about the color-changing and antioxidant mechanisms of ACN-based indicator films in food packaging.
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http://dx.doi.org/10.1080/10408398.2021.1959296DOI Listing
August 2021

Effects of ultrasonic treatment and homogenization on physicochemical properties of okara dietary fibers for 3D printing cookies.

Ultrason Sonochem 2021 Sep 25;77:105693. Epub 2021 Jul 25.

College of Food Science, Sichuan Agricultural University, Yaan 625014, China. Electronic address:

This paper presents a means to modify the attributes of okara fiber using ultrasonic and high-speed shearing treatment. The results of scanning electron microscopy and differential scanning calorimetry reveal that the modified okara fiber demonstrates small particle size and high thermal stability. When the 500 W-15,000 rpm combination is used for okara-fiber treatment, the latter exhibits excellent swelling (SC) as well as water- and oil-holding capacities. When 6% of modified okara fiber is added to the dough, the resulting cookies demonstrate the best printing performance. Subsequently, the printing parameters can be optimized to obtain the best filling rate of 30%. The corresponding nozzle diameter and printing speed equal 0.8 mm and 50 mm/s, respectively. Finally, the 3D-printed cookies containing okara fiber are compared against those commonly available in the market via sensory evaluation. As observed, the 3D-printed cookies were more acceptable to people. Therefore, the addition of the okara dietary fiber to the cookie dough not only improves the okara utilization rate but also increases the dietary-fiber content in the cookie, thereby alleviating the occurrence of obesity in modern society.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348173PMC
September 2021

Development and characterization of aldehyde-sensitive cellulose/chitosan/beeswax colorimetric papers for monitoring kiwifruit maturity.

Int J Biol Macromol 2021 Sep 23;187:566-574. Epub 2021 Jul 23.

College of Food Science, Sichuan Agricultural University, Yaan 625014, China. Electronic address:

In this study, we developed an in-package colorimetric paper to monitor the ripeness of kiwifruit by detecting the release of aldehydes. Strongly hydrophobic composite films were prepared using chitosan as the matrix and beeswax as an additive. A piece of cellulose paper containing methyl red and bromocresol violet as color indicators was heat-sealed between two hydrophobic films to protect the indicators from the effects of fruit respiration and transpiration. The nucleophilic addition reaction between aldehydes and OH (Cannizzaro reaction) changes the pH in the paper and triggers a color change in the indicators. As the kiwifruit ripens, the colorimetric paper changes from bluish-purple to dark red and then gradually to red. A mobile phone application was further used to measure the RGB values and link them to kiwifruit ripeness. This intelligent paper can be used for the accurate and convenient monitoring of produce in real time.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.132DOI Listing
September 2021

circPTPN12/miR-21-5 p/∆Np63α pathway contributes to human endometrial fibrosis.

Elife 2021 06 16;10. Epub 2021 Jun 16.

Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21-5 p to inhibit miR-21-5 p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC-EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC-EMT and administration of p could reverse this process and improve endometrial fibrosis. Our findings revealed that the dysfunction of circPTPN12/miR-21-5 p/∆Np63α pathway contributed to the pathogenesis of endometrial fibrosis.
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http://dx.doi.org/10.7554/eLife.65735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208816PMC
June 2021

Single-cell RNA sequencing reveals Nestin active neural stem cells outside the central canal after spinal cord injury.

Sci China Life Sci 2021 May 28. Epub 2021 May 28.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.

Neural stem cells (NSCs) in the spinal cord hold great potential for repair after spinal cord injury (SCI). The ependyma in the central canal (CC) region has been considered as the NSCs source in the spinal cord. However, the ependyma function as NSCs after SCI is still under debate. We used Nestin as a marker to isolate potential NSCs and their immediate progeny, and characterized the cells before and after SCI by single-cell RNA-sequencing (scRNA-seq). We identified two subgroups of NSCs: the subgroup located within the CC cannot prime to active NSCs after SCI, while the subgroup located outside the CC were activated and exhibited the active NSCs properties after SCI. We demonstrated the comprehensive dynamic transcriptome of NSCs from quiescent to active NSCs after SCI. This study reveals that Nestin cells outside CC were NSCs that activated upon SCI and may thus serve as endogenous NSCs for regenerative treatment of SCI in the future.
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http://dx.doi.org/10.1007/s11427-020-1930-0DOI Listing
May 2021

Scar tissue removal-activated endogenous neural stem cells aid Taxol-modified collagen scaffolds in repairing chronic long-distance transected spinal cord injury.

Biomater Sci 2021 Jul 27;9(13):4778-4792. Epub 2021 May 27.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

Scar tissue removal combined with biomaterial implantation is considered an effective measure to repair chronic transected spinal cord injury (SCI). However, whether more scar tissue removal surgeries could affect the treatment effects of biomaterial implantation still needs to be explored. In this study, we performed the first scar tissue removal surgery in the 3 month and the second in the 6 month after completely removing 1 cm of spinal tissue in canines. We found that Taxol-modified linear ordered collagen scaffold (LOCS + Taxol) implantation could promote axonal regeneration, neurogenesis, and electrophysiological and functional recovery only in canines at the first scar tissue removal surgery, but not in canines at the second scar tissue removal surgery. Interestingly, we found that more endogenous neural stem cells (NSCs) around the injured site could be activated in canines with the first rather than the second scar tissue removal. Furthermore, we demonstrated that Taxol could promote the neuronal differentiation of NSCs in the myelin inhibition microenvironment through the p38 MAPK signaling pathway in vitro. Therefore, we speculated that endogenous NSC activation by the first scar tissue removal surgery and its further differentiation into neurons induced by Taxol may contribute to functional recovery in canines. Together, LOCS + Taxol implantation in combination with the first scar tissue removal provides a promising therapy for chronic long-distance transected SCI repair with the help of scar tissue removal activated endogenous NSCs.
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http://dx.doi.org/10.1039/d1bm00449bDOI Listing
July 2021

Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury.

Stem Cell Res Ther 2021 05 26;12(1):300. Epub 2021 May 26.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

Background: Microtubule-stabilizing agents have been demonstrated to modulate axonal sprouting during neuronal disease. One such agent, Epothilone D, has been used to treat spinal cord injury (SCI) by promoting axonal sprouting at the lesion site after SCI. However, the role of Epothilone D in the differentiation of neural stem cells (NSCs) in SCI repair is unknown. In the present study, we mainly explored the effects and mechanisms of Epothilone D on the neuronal differentiation of NSCs and revealed a potential new SCI treatment.

Methods: In vitro differentiation assays, western blotting, and quantitative real-time polymerase chain reaction were used to detect the effects of Epothilone D on NSC differentiation. Retrograde tracing using a pseudotyped rabies virus was then used to detect neuronal circuit construction. RNA sequencing (RNA-Seq) was valuable for exploring the target gene involved in the neuronal differentiation stimulated by Epothilone D. In addition, lentivirus-induced overexpression and RNA interference technology were applied to demonstrate the function of the target gene. Last, an Apol8-NSC-linear ordered collagen scaffold (LOCS) graft was prepared to treat a mouse model of SCI, and functional and electrophysiological evaluations were performed.

Results: We first revealed that Epothilone D promoted the neuronal differentiation of cultured NSCs and facilitated neuronal relay formation in the injured site after SCI. Furthermore, the RNA-Seq results demonstrated that Apol8 was upregulated during Epothilone D-induced neuronal relay formation. Lentivirus-mediated Apol8 overexpression in NSCs (Apol8-NSCs) promoted NSC differentiation toward neurons, and an Apol8 interference assay showed that Apol8 had a role in promoting neuronal differentiation under the induction of Epothilone D. Last, Apol8-NSC transplantation with LOCS promoted the neuronal differentiation of transplanted NSCs in the lesion site as well as synapse formation, thus improving the motor function of mice with complete spinal cord transection.

Conclusions: Epothilone D can promote the neuronal differentiation of NSCs by upregulating Apol8, which may provide a promising therapeutic target for SCI repair.
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http://dx.doi.org/10.1186/s13287-021-02375-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157417PMC
May 2021

High strength pure chitosan hydrogels via double crosslinking strategy.

Biomed Mater 2021 06 28;16(4). Epub 2021 Jun 28.

Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, People's Republic of China.

Chitosan (CS) hydrogels have been widely used throughout basic tissue engineering and regenerative medicine research and it is very desirable to develop advanced CS materials with superior mechanical and topographical properties for more extensive applications. Herein, we present the design of a double crosslinking pure CS hydrogel material via the synergic effect of the chemical covalent network, hydrophobic interactions, enhanced intermolecular hydrogen bonding and the formation of the CS crystallite. The resultant pure CS hydrogel possesses increases in strength and toughness by two orders of magnitude (fracture energy ∼7.733 J m; maximal compression stress ∼10.81 MPa, elastic modulus ∼1.33 MPa). We utilizeH NMR and FT-IR to prove the success of chemical modification. The results of Raman spectra and WXRD have proved the existence of physical interaction between CS hydrogels and microcrystals, thus explaining the enhancement mechanism of mechanical strength of CS hydrogel. The live and death results also show that MSCs can grow well on CS hydrogels, and the results of CCK-8 indicate low cytotoxicity of CS hydrogels. This CS hydrogel shows great potential applications in tissue engineering and regenerative medicine.
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http://dx.doi.org/10.1088/1748-605X/ac058cDOI Listing
June 2021

The Rotary Cell Culture System increases NTRK3 expression and promotes neuronal differentiation and migratory ability of neural stem cells cultured on collagen sponge.

Stem Cell Res Ther 2021 05 21;12(1):298. Epub 2021 May 21.

Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, 100190, China.

Background: Recently, neural stem cell (NSC) therapy has shown promise for the treatment of many neurological diseases. Enhancing the quality of implanted cells and improving therapeutic efficacy are currently research hotspots. It has been reported that collagen sponge material provided sufficient room for cell growth in all directions and promoted the absorption of nutrients and removal of wastes. And also, the Rotary Cell Culture System (RCCS), which mimics the microgravity environment, can be used to culture cells for tissue engineering.

Materials And Methods: We performed the mRNA and miRNA sequencing to elucidate the regulatory mechanism of NSCs cultured on the collagen sponge in the RCCS system. The luciferase assay and Western blot revealed a direct regulatory role between let-7i-5p and neurotrophic receptor tyrosine kinase 3 (NTRK3; also called TrkC). And then, the neural differentiation markers Tuj1 and Map2 were detected by immunofluorescence staining. In the meantime, the migratory ability of NSCs was detected both in vitro and in spinal cord injury animals.

Results: In this study, we demonstrated that the expression of NTRK3 was elevated in NSCs cultured on collagen sponge in the RCCS system. Furthermore, increased NTRK3 expression was regulated by the downregulation of let-7i-5p. Compared to traditionally cultured NSCs, the NSCs cultured on collagen sponge in the RCCS system exhibited better neuronal differentiation and migratory ability, especially in the presence of NT-3.

Conclusions: As the biological properties and quality of transplanted cells are critical for therapeutic success, the RCCS system combined with the collagen sponge culture system shows promise for applications in clinical practice in the future.
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http://dx.doi.org/10.1186/s13287-021-02381-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139048PMC
May 2021

3D bioprinted neural tissue constructs for spinal cord injury repair.

Biomaterials 2021 05 25;272:120771. Epub 2021 Mar 25.

CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China; School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China. Electronic address:

Three-dimensional (3D) bioprinting has emerged as a promising approach to fabricate living neural constructs with anatomically accurate complex geometries and spatial distributions of neural stem cells (NSCs) for spinal cord injury (SCI) repair. The NSC-laden 3D bioprinting, however, still faces some big challenges, such as cumbersome printing process, poor cell viability, and minimal cell-material interaction. To address these issues, we have fabricated NSC-laden scaffolds by 3D bioprinting and explore for the first time their application for in vivo SCI repair. In our strategy, we have developed a novel biocompatible bioink consisting of functional chitosan, hyaluronic acid derivatives, and matrigel. This bioink shows fast gelation (within 20 s) and spontaneous covalent crosslinking capability, facilitating convenient one-step bioprinting of spinal cord-like constructs. Thus-fabricated scaffolds maintain high NSC viability (about 95%), and offer a benign microenvironment that facilitates cell-material interactions and neuronal differentiation for optimal formation of neural network. The in vivo experiment has further demonstrated that the bioprinted scaffolds promoted the axon regeneration and decreased glial scar deposition, leading to significant locomotor recovery of the SCI model rats, which may represent a general and versatile strategy for precise engineering of central nervous system and other neural organs/tissues for regenerative medicine application.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120771DOI Listing
May 2021

Lineage tracing reveals the origin of Nestin-positive cells are heterogeneous and rarely from ependymal cells after spinal cord injury.

Sci China Life Sci 2021 Mar 24. Epub 2021 Mar 24.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, China.

Nestin is expressed extensively in neural stem/progenitor cells during neural development, but its expression is mainly restricted to the ependymal cells in the adult spinal cord. After spinal cord injury (SCI), Nestin expression is reactivated and Nestin-positive (Nestin) cells aggregate at the injury site. However, the derivation of Nestin cells is not clearly defined. Here, we found that Nestin expression was substantially increased in the lesion edge and lesion core after SCI. Using a tamoxifen inducible CreER(T2)-loxP system, we verified that ependymal cells contribute few Nestin cells either to the lesion core or the lesion edge after SCI. In the lesion edge, GFAP astrocytes were the main cell type that expressed Nestin; they then formed an astrocyte scar. In the lesion core, Nestin cells expressed αSMA or Desmin, indicating that they might be derived from pericytes. Our results reveal that Nestin cells in the lesion core and edge came from various cell types and rarely from ependymal cells after complete transected SCI, which may provide new insights into SCI repair.
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http://dx.doi.org/10.1007/s11427-020-1901-4DOI Listing
March 2021

Dual-Cues Laden Scaffold Facilitates Neurovascular Regeneration and Motor Functional Recovery After Complete Spinal Cord Injury.

Adv Healthc Mater 2021 05 19;10(10):e2100089. Epub 2021 Mar 19.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.

Complete transection spinal cord injury (SCI) severely disrupts the integrity of both neural circuits and the microvasculature system. Hence, fabricating a functional bio-scaffold that could coordinate axonal regeneration and vascular reconstruction in the lesion area may emerge as a new paradigm for complete SCI repair. In this study, a photosensitive hydrogel scaffold loaded with collagen-binding stromal cell-derived factor-1a and Taxol liposomes is capable of inducing migration of endothelial cells and promoting neurite outgrowth of neurons in vitro. In addition, when implanted into a rat T8 complete transection SCI model, the above dual-cues laden scaffold exhibits a synergistic effect on facilitating axon and vessel regeneration in the lesion area within 10 days after injury. Moreover, long-term therapeutic effects are also observed after dual-cues laden scaffold implantation, including revascularization, descending and propriospinal axonal regeneration, fibrotic scar reduction, electrophysiological recovery, and motor function improvement. In summary, the dual-cues laden scaffold has good clinical application potential for patients with severe SCI.
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http://dx.doi.org/10.1002/adhm.202100089DOI Listing
May 2021

Electrospun nanofibers food packaging: trends and applications in food systems.

Crit Rev Food Sci Nutr 2021 Mar 16:1-14. Epub 2021 Mar 16.

College of Food Science, Sichuan Agricultural University, Ya'an, China.

Food safety is a bottleneck problem. In order to provide information about advanced and unique food packaging technique, this study summarized the advancements of electrospinning technique. Food packaging is a multidisciplinary area involving food science, food engineering, food chemistry, and food microbiology, and the interest in maintaining the freshness and quality of foods has grown considerably. For this purpose, electrospinning technology has gained much attention due to its unique functions and superior processing. Sudden advancements of electrospinning have been rapidly incorporated into research. This review summarized some latest information about food packaging and different materials used for the packaging of various foods such as fruits, vegetables, meat, and processed items. Also, the use of electrospinning and materials used for the formation of nanofibers are discussed in detail. However, in food industry, the application of electrospun nanofibers is still in its infancy. In this study, different parameters, structures of nanofibers, features and fundamental properties are described briefly, while polymers fabricated through electrospinning with advances in food packaging films are described in detail. Moreover, this comprehensive review focuses on the polymers used for the electrospinning of nanofibers as packaging films and their applications for variety of foods. This will be a valuable source of information for researchers studying various polymers for electrospinning for application in the food packaging industry.
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http://dx.doi.org/10.1080/10408398.2021.1899128DOI Listing
March 2021

Direct neuronal differentiation of neural stem cells for spinal cord injury repair.

Stem Cells 2021 Aug 5;39(8):1025-1032. Epub 2021 Mar 5.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People's Republic of China.

Spinal cord injury (SCI) typically results in long-lasting functional deficits, largely due to primary and secondary white matter damage at the site of injury. The transplantation of neural stem cells (NSCs) has shown promise for re-establishing communications between separated regions of the spinal cord through the insertion of new neurons between the injured axons and target neurons. However, the inhibitory microenvironment that develops after SCI often causes endogenous and transplanted NSCs to differentiate into glial cells rather than neurons. Functional biomaterials have been shown to mitigate the effects of the adverse SCI microenvironment and promote the neuronal differentiation of NSCs. A clear understanding of the mechanisms of neuronal differentiation within the injury-induced microenvironment would likely allow for the development of treatment strategies designed to promote the innate ability of NSCs to differentiate into neurons. The increased differentiation of neurons may contribute to relay formation, facilitating functional recovery after SCI. In this review, we summarize current strategies used to enhance the neuronal differentiation of NSCs through the reconstruction of the SCI microenvironment and to improve the intrinsic neuronal differentiation abilities of NSCs, which is significant for SCI repair.
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http://dx.doi.org/10.1002/stem.3366DOI Listing
August 2021

Binary scaffold facilitates in situ regeneration of axons and neurons for complete spinal cord injury repair.

Biomater Sci 2021 Apr 26;9(8):2955-2971. Epub 2021 Feb 26.

Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China. and Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha 410008, Hunan Province, China and Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

The limited regrowth of transected axons and insufficient regeneration of lost neurons in adult mammals collectively hinder complete spinal cord injury (SCI) repair. Hence, designing an ideal bio-scaffold which could coordinate the regeneration of axons and neurons in situ might be able to effectively facilitate the reconstruction of neural circuits and the recovery of nerve function after complete SCI. In this study, a sponge-like collagen scaffold with good drug release characteristics and good nerve cell compatibility was prepared and used as a drug delivery platform. When doubly modified with Taxol liposomes and collagen-binding neurotrophic factor 3, the scaffold dually alleviated myelin-derived inhibition on neurite outgrowth of neurons and neuronal differentiation of neural stem cells in vitro. Meanwhile, the binary-drug modified scaffold was also able to simultaneously promote both axonal and neuronal regeneration when implanted into a complete transected SCI model. Additionally, the regenerated axons and neurons throughout the lesion site formed extensive synaptic connections. Finally, complete SCI rats that received binary scaffold implantation exhibited optimal neuroelectrophysiological recovery and hindlimb locomotor improvement. Taken together, implantation of the binary scaffold can establish neural bridging networks for functional recovery, representing a clinically promising strategy for complete SCI repair.
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http://dx.doi.org/10.1039/d0bm02212hDOI Listing
April 2021

Preparation of polylactic acid/TiO/GO nano-fibrous films and their preservation effect on green peppers.

Int J Biol Macromol 2021 Apr 18;177:135-148. Epub 2021 Feb 18.

College of Food Science, Sichuan Agricultural University, Ya'an 625014, China; California Nano Systems Institute, University of California, Los Angeles, CA 90095, USA. Electronic address:

Polylactic acid (PLA)/nano-TiO(TiO NPs)/Graphene oxide (GO) nano-fibrous films were prepared by ultrasonic assisted electrostatic spinning technology, and the effects of TiO NPs:GO mass ratio and ultrasonic power on film morphology and mechanical, thermal, barrier and antibacterial properties were investigated. The addition of TiO NPs and GO can significantly increase the tensile strength and elongation at the break of PLA nano-fibrous films, and improve the water barrier properties of the nano-fibrous films. The antibacterial experiment showed that the inhibition rates of the nano-fibrous films against Escherichia coli and Staphylococcus aureus after 24 h exposure to UV irradiation reached 94.4 ± 1.8% and 92.6 ± 1.7% At the same time, the fresh-keeping packaging experiment of green peppers at room temperature, through the determination of hardness, soluble solids, chlorophyll content to determine the degree of decay of green pepper, it showed that PLA/TiO NPs/GO nano-fibrous films can better maintain the sensory quality of green peppers, delay the rate of spoilage of green peppers, and prolong the preservation period of green peppers.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.125DOI Listing
April 2021

NSCs Migration Promoted and Drug Delivered Exosomes-Collagen Scaffold via a Bio-Specific Peptide for One-Step Spinal Cord Injury Repair.

Adv Healthc Mater 2021 04 1;10(8):e2001896. Epub 2021 Feb 1.

Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.

Spinal cord injury (SCI) is plaguing medical professionals globally due to the complexity of injury progression. Based on tissue engineering technology, there recently emerges a promising way by integrating drugs with suitable scaffold biomaterials to mediate endogenous neural stem cells (NSCs) to achieve one-step SCI repair. Herein, exosomes extracted from human umbilical cord-derived mesenchymal stem cells (MExos) are found to promote the migration of NSCs in vitro/in vivo. Utilizing MExos as drug delivery vehicles, a NSCs migration promoted and paclitaxel (PTX) delivered MExos-collagen scaffold is designed via a novel dual bio-specificity peptide (BSP) to effectively retain MExos within scaffolds. By virtue of the synergy that MExos recruit endogenous NSCs to the injured site, and PTX induce NSCs to give rise to neurons, this multifunctional scaffold has shown superior performance for motor functional recovery after complete SCI in rats by enhancing neural regeneration and reducing scar deposition. Besides, the dual bio-specific peptide demonstrates the capacity of tethering other cells-derived exosomes on collagen scaffold, such as erythrocytes-derived or NSCs-derived exosomes on collagen fibers or membranes. The resulting exosomes-collagen scaffold may serve as a potential multifunctional therapy modality for various disease treatments including SCI.
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http://dx.doi.org/10.1002/adhm.202001896DOI Listing
April 2021

Comparison of Regenerative Effects of Transplanting Three-Dimensional Longitudinal Scaffold Loaded-Human Mesenchymal Stem Cells and Human Neural Stem Cells on Spinal Cord Completely Transected Rats.

ACS Biomater Sci Eng 2020 03 19;6(3):1671-1680. Epub 2020 Feb 19.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing 100101, China.

Stem cell-based therapy has been considered as a potential treatment to restore spinal cord injury (SCI) through reconstructing neural networks and providing a favorable microenvironment for neuronal survival, differentiation, and axonal outgrowth. Biomaterial scaffolds can promote cell attachment and survival, neuronal differentiation, and axonal outgrowth; therefore, they were used to combine with stem cells for implantation in SCI treatment. In addition, a longitudinal scaffold can guide regenerated axons with orientated growth and axial extension. Both human umbilical cord-derived mesenchymal stem cells (hMSCs) and human fetal spinal cord-derived neural stem cells (hNSCs) have been applied in clinical trials worldwide. To our knowledge, a parallel comparison of the therapeutic effects of hMSC and hNSC implantations has not been conducted. Hence, in this study, we grafted hMSCs or hNSCs seeded on longitudinal collagen sponge scaffolds into rats with completely transected SCI to examine differences in SCI repair. Both hMSCs and hNSCs had equivalent effects on reducing glial scar formation around the lesion gap. More neuronal class III β-tubulin-positive neurons and neurofilament-positive nerve fibers were found in the lesion cavity after hNSC implantation. In addition, hNSCs had better capabilities to improve motor function, attenuate inflammation, and promote cell survival than hMSCs. These encouraging results provide a clinical basis for future stem cell-based SCI therapies.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01790DOI Listing
March 2020

Research progress on antimicrobial materials for food packaging.

Crit Rev Food Sci Nutr 2020 Dec 23:1-14. Epub 2020 Dec 23.

College of Food Science, Sichuan Agricultural University, Ya'an, China.

Microbial contamination is an utmost cause of food spoilage. Antimicrobial agents are used to treat microbial diseases in food. They also serve food packaging industry, as they are used for the formation of antimicrobial packaging films which maintain the structure, texture, color, and nutrition value of food. Due to ever growing population, the demands of food are also rising. There is need to stop food wastage and to prevent spoilage. Most of the food is spoiled during harvesting, transportation, and distribution. This is a serious problem to overcome. Adding antibacterial agents is the most convenient way to reduce food spoilage and contamination. To support the characteristics and properties of antibacterial materials, different modifications are performed in the field of food packaging, which is one of the most demanding techniques for food preservation. This review will summarize the research about antimicrobial agents, with an emphasis on recent findings, to highlight the importance of new developments in this field. Concepts of antimicrobial packaging with a focus on antibiotics and antibacterial agents are discussed briefly in this review, along with the different types of food packaging and applications of antimicrobial packaging. Synthetic and natural antimicrobial materials are described. In summary, this article will explain the importance of antibacterial agents and their use in food packaging industry. Furthermore, readers will get good information about natural antibacterial polymers which were extensively used in past few decades. Subsequently, different innovations should be done to control food spoilage and wastage to ensure food safety. Food packaging is a sole element that helps to provide safe and secure food for all.
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http://dx.doi.org/10.1080/10408398.2020.1863327DOI Listing
December 2020

Spatiotemporal dynamic changes, proliferation, and differentiation characteristics of Sox9-positive cells after severe complete transection spinal cord injury.

Exp Neurol 2021 03 14;337:113556. Epub 2020 Dec 14.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100190, China; Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China. Electronic address:

Studying the spatiotemporal dynamic changes of various cells following spinal cord injury (SCI) is of great significance for understanding the pathological processes of SCI. Changes in the characteristics of Sox9-positive cells, which are widely present in the spinal cord, have rarely been studied following SCI. We found that Sox9-positive cells were widely distributed in the central canal and parenchyma of the uninjured adult spinal cord, with the greatest distribution in the central spinal cord and relatively few cells in the dorsal and ventral sides. Ranging between 14.20% ± 1.61% and 15.60% ± 0.36% of total cells in the spinal cord, almost all Sox9-positive cells were in a quiescent state. However, Sox9-positive cells activated following SCI exhibited different characteristics according to their distance from the lesion area. In the reactive region, Sox9-positive cells highly expressed nestin and exhibited a single-branching structure, whereas in the non-reactive region, cells showed low nestin expression and a multi-branching structure. In response to SCI, a large number of Sox9-positive cells in the spinal cord parenchyma proliferated to participate in the formation of glial scars, whereas Sox9-positive cells in the central canal located near the lesion site accumulated at its broken ends through proliferation. Finally, we found that approximately 6.30% ± 0.35% of Sox9-positive cells differentiated into oligodendrocytes within two weeks after SCI. By examining the spatiotemporal dynamic changes, proliferation and differentiation characteristics of Sox9-positive cells after SCI, our findings provide a theoretical basis for understanding the pathological process of SCI.
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http://dx.doi.org/10.1016/j.expneurol.2020.113556DOI Listing
March 2021

Small molecules combined with collagen hydrogel direct neurogenesis and migration of neural stem cells after spinal cord injury.

Biomaterials 2021 02 15;269:120479. Epub 2020 Nov 15.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Complete spinal cord injury (SCI) leads to cell death, interruption of axonal connections and permanent functional impairments. In the development of SCI treatments, cell transplantation combined with biomaterial-growth factor-based therapies have been widely studied. Another avenue worth exploring is the generation of neurons from endogenous neural stem cells (NSCs) or reactive astrocytes activated by SCI. Here, we screened a combination of four small molecules, LDN193189, SB431542, CHIR99021 and P7C3-A20, that can increase neuronal differentiation of mouse and rat spinal cord NSCs. Moreover, the small molecules loaded in an injectable collagen hydrogel induced neurogenesis and inhibited astrogliogenesis of endogenous NSCs in the injury site, which usually differentiate into astrocytes under pathological conditions. Meanwhile, induced neurons migrated into the non-neural lesion core, and genetic fate mapping showed that neurons mainly originated from NSCs in the parenchyma, but not from the central canal of the spinal cord. The neuronal regeneration in the lesion sites resulted in some recovery of locomotion. Our findings indicate that the combined treatment of small molecules and collagen hydrogel is a potential therapeutic strategy for SCI by inducing in situ endogenous NSCs to form neurons and restore damaged functions.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120479DOI Listing
February 2021

Optimization, characterization and evaluation of papaya polysaccharide-corn starch film for fresh cut apples.

Int J Biol Macromol 2021 Jan 4;166:1057-1071. Epub 2020 Nov 4.

College of Food Science, Sichuan Agricultural University, Yaan 625014, China; California Nano Systems Institute, University of California, Los Angeles, CA 90095, USA. Electronic address:

In this study, we prepared corn starch (CS) and papaya polysaccharide (PPs) films using the solution casting technique. A Box-Behnken experimental design was used to determine the effect of ethanol concentration, extraction duration, and material concentration during PPs extraction. The resulting films were characterized in terms of structural changes, physical, optical, mechanical, Fourier-transform infrared (FTIR) spectroscopy, and thermal properties. The results show that PPs-CS composite films have good antioxidant and moisturizing properties and general antibacterial performance. These results revealed that after adding PPs, the films exhibited a significant increase in swelling and tensile strength, while depicted a reduction in thickness, transparency, and solubility. SEM images revealed that PPs and CS are highly compatible; moreover, FTIR spectroscopy showed that intermolecular hydrogen bonding existed between CS and PPs, forming a compact film structure. Finally, the incorporation of PPs and CS influenced the shelf-life of fresh cut apples, with the edible film incorporated with PPs positively improving sensory acceptance of combined materials.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.10.261DOI Listing
January 2021

Improving nisin production by encapsulated Lactococcus lactis with starch/carboxymethyl cellulose edible films.

Carbohydr Polym 2021 Jan 9;251:117062. Epub 2020 Sep 9.

College of Food Science, Sichuan Agricultural University, Yaan, 625014, China; California Nano Systems Institute, University of California, Los Angeles, CA, 90095, USA. Electronic address:

In this study, Lactococcus lactis was embedded in a film of corn starch (NS) and carboxymethyl cellulose (CMC) prepared using a casting method. At a CMC:NS ratio of 5:5, the composite film had the best comprehensive properties. Scanning electron microscopy images clearly showed that L. lactis was effectively embedded. The film with 1.5 % L. lactis showed the best performance and the lowest water vapor transmission rate (5.54 × 10 g/m s Pa. In addition, the edible film retained a viable count of 5.64 log CFU/g of L. lactis when stored at 4 °C for 30 days. The composite film with 1.5 % L. lactis showed the highest release of nisin (3.35 mg/mL) and good antibacterial activity against Staphylococcus aureus (53.53 %) after 8 days. Therefore, this edible film is a viable alternative antimicrobial strategy for the active packaging of foods containing low moisture content.
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http://dx.doi.org/10.1016/j.carbpol.2020.117062DOI Listing
January 2021
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