Publications by authors named "Sa Xiao"

118 Publications

Inhibition of TNFAIP1 ameliorates the oxidative stress and inflammatory injury in myocardial ischemia/reperfusion injury through modulation of Akt/GSK-3β/Nrf2 pathway.

Int Immunopharmacol 2021 Jul 27;99:107993. Epub 2021 Jul 27.

Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address:

Tumor necrosis factor α-induced protein 1 (TNFAIP1) has been documented as a vital regulator of apoptosis and oxidative stress under various pathological conditions. However, whether TNFAIP1 plays a role in myocardial ischemia/reperfusion (I/R) injury has not been well investigated. This work aimed to evaluate the possible role of TNFAIP1 in mediating myocardial I/R injury. Firstly, we demonstrated that TNFAIP1 expression was dramatically increased in rat cardiomyocytes following hypoxia/reoxygenation (H/R) in vitro, and in rat myocardial tissues following I/R treatment in vivo. Silencing of TNFAIP1 alleviated H/R-induced apoptosis, oxidative stress and inflammatory response in rat cardiomyocytes in vitro. Moreover, knockdown of TNFAIP1 ameliorated I/R-induced myocardial injury, infarction size, cardiac apoptosis, oxidative stress and inflammatory response in vivo. Further investigation elucidated that knockdown of TNFAIP1 enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with modulation of the Akt/glycogen synthase kinase-3β (GSK-3β) pathway in vitro and in vivo. Inhibition of Akt markedly abrogated TNFAIP1-knockdown-mediated Nrf2 activation in cardiomyocytes following H/R injury. In addition, suppression of Nrf2 significantly diminished TNFAIP1-knockdown-induced cardioprotective effects in H/R-exposed cardiomyocytes. In summary, this work elucidates that inhibition of TNFAIP1 ameliorates myocardial I/R injury by potentiating Nrf2 signaling via the modulation of the Akt/GSK-3β pathway. Our study highlights a vital role of the TNFAIP1/Akt/GSK-3β/Nrf2 pathway in mediating myocardial I/R injury and suggests TNFAIP1 as an attractive target for treatment of this disease.
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http://dx.doi.org/10.1016/j.intimp.2021.107993DOI Listing
July 2021

Newcastle disease virus V protein interacts with hnRNP H1 to promote viral replication.

Vet Microbiol 2021 Jun 30;260:109093. Epub 2021 Jun 30.

College of Veterinary Medicine, Northwest A & F University, Yangling, Shaanxi, 712100, China. Electronic address:

The interactions between host cellular proteins and viral proteins are important for successful infection by viruses. Previous studies from our group have identified various host cellular proteins that can interact with the Newcastle disease virus V protein (Chu et al., 2018a), but their function in NDV replication has not been fully determined. The present study reports that heterogenous nuclear ribonucleoprotein H1 (hnRNP H1) can interact with NDV V protein in yeast. The immunofluorescence results showed that hnRNP H1 and V protein could colocalize in the cytoplasm of a chicken embryo fibroblast cell line (DF-1 cells). Co-immunoprecipitation assays further verified the interaction of these two proteins. The effects of overexpression and knockdown of hnRNP H1 on NDV replication were evaluated in DF-1 cells through real time quantitative PCR (RT-qPCR) and plaque assays. The regulation of V protein on hnRNP H1 expression was also examined. The results indicated that overexpression of hnRNP H1 facilitated NDV replication, while knockdown of hnRNP H1 decreased NDV replication. It was also shown that V protein could regulate hnRNP H1 expression at the protein level instead of the transcription level. The effect of V protein and hnRNP H1 on the DF-1 cell cycle was also tested and the results revealed that V protein may regulate cell proliferation by controlling the expression of hnRNP H1. Taken together, these results suggest that NDV V protein could promote viral replication by interacting with hnRNP H1.
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http://dx.doi.org/10.1016/j.vetmic.2021.109093DOI Listing
June 2021

Accelerate gas diffusion-weighted MRI for lung morphometry with deep learning.

Eur Radiol 2021 Jul 13. Epub 2021 Jul 13.

Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences-Wuhan National Laboratory for Optoelectronics, Wuhan, 430071, People's Republic of China.

Objectives: Multiple b-value gas diffusion-weighted MRI (DW-MRI) enables non-invasive and quantitative assessment of lung morphometry, but its long acquisition time is not well-tolerated by patients. We aimed to accelerate multiple b-value gas DW-MRI for lung morphometry using deep learning.

Methods: A deep cascade of residual dense network (DC-RDN) was developed to reconstruct high-quality DW images from highly undersampled k-space data. Hyperpolarized Xe lung ventilation images were acquired from 101 participants and were retrospectively collected to generate synthetic DW-MRI data to train the DC-RDN. Afterwards, the performance of the DC-RDN was evaluated on retrospectively and prospectively undersampled multiple b-value Xe MRI datasets.

Results: Each slice with size of 64 × 64 × 5 could be reconstructed within 7.2 ms. For the retrospective test data, the DC-RDN showed significant improvement on all quantitative metrics compared with the conventional reconstruction methods (p < 0.05). The apparent diffusion coefficient (ADC) and morphometry parameters were not significantly different between the fully sampled and DC-RDN reconstructed images (p > 0.05). For the prospectively accelerated acquisition, the required breath-holding time was reduced from 17.8 to 4.7 s with an acceleration factor of 4. Meanwhile, the prospectively reconstructed results showed good agreement with the fully sampled images, with a mean difference of -0.72% and -0.74% regarding global mean ADC and mean linear intercept (L) values.

Conclusions: DC-RDN is effective in accelerating multiple b-value gas DW-MRI while maintaining accurate estimation of lung microstructural morphometry, facilitating the clinical potential of studying lung diseases with hyperpolarized DW-MRI.

Key Points: • The deep cascade of residual dense network allowed fast and high-quality reconstruction of multiple b-value gas diffusion-weighted MRI at an acceleration factor of 4. • The apparent diffusion coefficient and morphometry parameters were not significantly different between the fully sampled images and the reconstructed results (p > 0.05). • The required breath-holding time was reduced from 17.8 to 4.7 s and each slice with size of 64 × 64 × 5 could be reconstructed within 7.2 ms.
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http://dx.doi.org/10.1007/s00330-021-08126-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276538PMC
July 2021

Early prediction of lung lesion progression in COVID-19 patients with extended CT ventilation imaging.

Eur J Nucl Med Mol Imaging 2021 Jun 17. Epub 2021 Jun 17.

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences - Wuhan National Laboratory for Optoelectronics, Wuhan, 430071, China.

Purpose: In the prediction of COVID-19 disease progression, a clear illustration and early determination of an area that will be affected by pneumonia remain great challenges. In this study, we aimed to predict and visualize the progression of lung lesions in COVID-19 patients in the early stage of illness by using chest CT.

Methods: COVID-19 patients who underwent three chest CT scans in the progressive phase were retrospectively enrolled. An extended CT ventilation imaging (CTVI) method was proposed in this work that was adapted to use two chest CT scans acquired on different days, and then lung ventilation maps were generated. The prediction maps were obtained according to the fractional ventilation values, which were related to pulmonary regional function and tissue property changes. The third CT scan was used to validate whether the prediction maps could be used to distinguish healthy regions and potential lesions.

Results: A total of 30 patients (mean age ± SD, 43 ± 10 years, 19 females, and 2-12 days between the second and third CT scans) were included in this study. The predicted lesion locations and sizes were almost the same as the true ones visualized in third CT scan. Quantitatively, the predicted lesion volumes and true lesion volumes showed both a good Pearson correlation (R = 0.80; P < 0.001) and good consistency in the Bland-Altman plot (mean bias = 0.04 cm). Regarding the enlargements of the existing lesions, prediction results also exhibited a good Pearson correlation (R = 0.76; P < 0.001) with true lesion enlargements.

Conclusion: The present findings demonstrated that the extended CTVI method could accurately predict and visualize the progression of lung lesions in COVID-19 patients in the early stage of illness, which is helpful for physicians to predetermine the severity of COVID-19 pneumonia and make effective treatment plans in advance.
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http://dx.doi.org/10.1007/s00259-021-05435-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210511PMC
June 2021

Musashi1 inhibit the release of Newcastle disease viruses through preventing apoptosis of DF-1 cells.

Poult Sci 2021 Jul 11;100(7):101105. Epub 2021 Mar 11.

College of Veterinary Medicine, Northwest A & F University, Yangling, Shaanxi 712100, China. Electronic address:

The efficient proliferation of Newcastle disease virus (NDV) depends on its inhibition of host cell innate immunity. V protein acts as a nonstructural protein which plays a significant role in virus replication, whereas its function remains to be further explored. In this study, Musashi RNA binding protein 1 (MSI1) was selected and its interaction with V protein was further verified by Co-immunoprecipitation (Co-IP) and Immuno-colocalization test. Through the transfection of pCMV-HA-MSI1 in DF-1 cells, the overexpression of MSI1 reduced virus particles in the cell supernatant but not reduced mRNA and virus protein in cells pellet, which suggests that MSI1may act as a new antiviral molecule by inhibiting viral release. Cell early apoptosis was detected by flow cytometry (FCM), the result shows that overexpression of MSI1 inhibit cell apoptosis, implying MSI1 Inhibit virus release may through this way. Taken together, MSI1 and NDV V protein has a detectable interaction, and may block apoptosis to inhibit the release of NDV. However, this is the first report about the interaction between MSI1 and V protein of NDV that can inhibit the NDV replicated.
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http://dx.doi.org/10.1016/j.psj.2021.101105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173301PMC
July 2021

Effect of Nitrogen Addition on Selection of Germination Trait in an Alpine Meadow on the Tibet Plateau.

Front Plant Sci 2021 14;12:634850. Epub 2021 May 14.

State Key Laboratory of Grassland and Agro-Ecosystems, School of Life Sciences, Lanzhou University, Lanzhou, China.

Seed germination requirements may determine the kinds of habitat in which plants can survive. We tested the hypothesis that nitrogen (N) addition can change seed germination trait-environmental filter interactions and ultimately redistribute seed germination traits in alpine meadows. We determined the role of N addition on germination trait selection in an alpine meadow after N addition by combining a 3-year N addition experiment in an alpine meadow and laboratory germination experiments. At the species level, germination percentage, germination rate (speed) and breadth of temperature niche for germination (BTN) were positively related to survival of a species in the fertilized community. In addition, community-weighted means of germination percentage, germination rate, germination response to alternating temperature and BTN increased. However, germination response to wet-cold storage (cold stratification) and functional richness of germination traits was lower in alpine meadows with high-nitrogen addition than in those with no, low and medium N addition. Thus, N addition had a significant influence on environmental filter-germination trait interactions and generated a different set of germination traits in the alpine meadow. Further, the effect of N addition on germination trait selection by environmental filters was amount-dependent. Low and medium levels of N addition had less effect on redistribution of germination traits than the high level.
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http://dx.doi.org/10.3389/fpls.2021.634850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160428PMC
May 2021

Selection of high-quality sperm with thousands of parallel channels.

Lab Chip 2021 06 13;21(12):2464-2475. Epub 2021 May 13.

Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, Ontario M5S 3G8, Canada.

Sperm selection is essential for successful fertilization and embryo development. Current clinical sperm selection methods are labor-intensive and lack the selectivity required to isolate high-quality sperm. Microfluidic sperm selection approaches have shown promise but present a trade-off between the quality and quantity of selected sperm - clinicians demand both. The structure of the female reproductive tract helps to isolate a sufficient quantity of high-quality sperm for fertilization with densely folded epithelium that provides a multitude of longitudinally oriented pathways that guide sperm toward the fertilization site. Here, a three-dimensionally structured sperm selection device is presented that levers this highly parallelized in vivo mechanism for in vitro sperm selection. The device is inserted in a test tube atop 1 mL of raw semen and provides 6500 channels that isolate ∼100 000 high-DNA-integrity sperm for assisted reproduction. In side-by-side clinical testing, the developed approach outperforms the best current clinical methods by improving the DNA integrity of the selected sperm subpopulation up to 95%. Also, the device streamlines clinical workflow, reducing the time required for sperm preparation 3-fold. This single-tube, single-step sperm preparation approach promises to improve both the economics and outcomes of assisted reproduction practices, especially in cases with significant male-factors.
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http://dx.doi.org/10.1039/d0lc01182gDOI Listing
June 2021

Cellular CARD11 Inhibits the Fusogenic Activity of Newcastle Disease Virus via CBM Signalosome-Mediated Furin Reduction in Chicken Fibroblasts.

Front Microbiol 2021 2;12:607451. Epub 2021 Feb 2.

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

Newcastle disease virus (NDV) causes an infectious disease that poses a major threat to poultry health. Our previous study identified a chicken brain-specific caspase recruitment domain-containing protein 11 (CARD11) that was upregulated in chicken neurons and inhibited NDV replication. This raises the question of whether CARD11 plays a role in inhibiting viruses in non-neural cells. Here, chicken fibroblasts were used as a non-neural cell model to investigate the role. CARD11 expression was not significantly upregulated by either velogenic or lentogenic NDV infection in chicken fibroblasts. Viral replication was decreased in DF-1 cells stably overexpressing CARD11, while viral growth was significantly increased in the CARD11-knockdown DF-1 cell line. Moreover, CARD11 colocalized with the viral protein and aggregated around the fibroblast nucleus, suggesting that an interaction existed between CARD11 and the viral protein; this interaction was further examined by suppressing viral RNA polymerase activity by using a minigenome assay. Viral replication was inhibited by CARD11 in fibroblasts, and this result was consistent with our previous report in chicken neurons. Importantly, CARD11 was observed to reduce the syncytia induced by either velogenic virus infection or viral haemagglutinin-neuraminidase (HN) and F cotransfection in fibroblasts. We found that CARD11 inhibited the expression of the host protease furin, which is essential for cleavage of the viral protein to trigger fusogenic activity. Furthermore, the CARD11-Bcl10-MALT1 (CBM) signalosome was found to suppress furin expression, which resulted in a reduction in the cleavage efficiency of the viral protein to further inhibit viral syncytia. Taken together, our findings mainly demonstrated a novel CARD11 inhibitory mechanism for viral fusogenic activity in chicken fibroblasts, and this mechanism explains the antiviral roles of this molecule in NDV pathogenesis.
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http://dx.doi.org/10.3389/fmicb.2021.607451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884349PMC
February 2021

FertDish: microfluidic sperm selection-in-a-dish for intracytoplasmic sperm injection.

Lab Chip 2021 02;21(4):775-783

Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, Ontario M5S 3G8, Canada.

The selection of high quality sperm is critical for intracytoplasmic sperm injection (ICSI), a prevalent assisted reproduction technology. However, standard selection methods are time-consuming and fail to recover the most viable sperm, thereby limiting the ICSI success rate. Microfluidics enables rapid selection of viable sperm in a manner representing in vivo processes, however, existing platforms lack clinical applicability. Here, we present FertDish, which integrates the clinically established ICSI Petri dish with a film featuring an array of sperm-selecting microchannels for selection of sperm directly from semen. The FertDish format mimics the clinician-familiar ICSI dish setup, and provides rapid (<10 min) single stage sperm preparation that circumvents standard labour-intensive multi-stage sperm processing steps. Tests with human donor and patient semen samples show that FertDish enables the selection of a high quality sperm sub-population, featuring improvements in DNA fragmentation index of more than 91% (donor) and 74% (patient) versus raw semen and 50% (donor) and 63% (patient) versus standard methods, and a distribution of more than 97% sperm with viable and high level DNA. The FertDish enables a high sperm recovery rate (>3.3 × 105 sperm per mL), and is readily adaptable to the clinical workflow with potential to improve ICSI outcomes.
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http://dx.doi.org/10.1039/d0lc00874eDOI Listing
February 2021

Comparative biology of two genetically closely related Newcastle disease virus strains with strongly contrasting pathogenicity.

Vet Microbiol 2021 Feb 29;253:108977. Epub 2020 Dec 29.

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi Province, 712100, PR China. Electronic address:

A lentogenic strain of Newcastle disease virus (NDV) with an intracerebral pathogenicity index (ICPI) of 0.36 was derived by the passage of a mesogenic NDV isolate with an original ICPI of 1.04. Animal experiments showed that the original strain caused much severer clinical signs and mortality than the derived strain in chickens. To elucidate the molecular reason for this virulence change, the complete viral genomes of the original and derived strains were sequenced. Molecular analysis showed that both viruses contained the same fusion (F) protein with a cleavage site (Fcs) motif that is usually associated with velogenic viruses. Molecular comparison revealed five amino acid (aa) differences in nucleoprotein (NP) (aa 426), hemagglutinin-neuraminidase (HN) (aas 215 and 430), and large protein (L) (aas 1694 and 1767), accompanied by the changes of relevant biological activities in membrane fusion and replication. Thus, we believe that the virulence changes may induced by these mutations. Our findings make a foundation for more in-depth investigations of the molecular mechanism underlying virulence.
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http://dx.doi.org/10.1016/j.vetmic.2020.108977DOI Listing
February 2021

Identification of a potential neutralizing linear epitope of hemagglutinin-neuraminidase in Newcastle disease virus.

Virol J 2021 01 6;18(1). Epub 2021 Jan 6.

College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shanxi, People's Republic of China.

Background: The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) is a major antigen that can induce protective antibodies in poultry. However, its antigenic epitopes have not been fully elucidated. Therefore, defining the linear epitopes of HN, especially neutralizing epitopes, will be useful for revealing its antigenic characterization.

Methods: In this study, we analyzed B-cell immunodominant epitopes (IDEs) of the HN protein from the vaccine strain LaSota using pepscan technology with LaSota-specific chicken hyperimmune antisera. We constructed IDEs-RFP plasmids and prepared anti-IDEs peptide mouse sera to identify IDEs through immunological tests. At last, the different diluted anti-IDE antisera were used in BHK-21 cells to perform the neutralization test.

Results: Five IDEs of the HN were screened and further verified by indirect immunofluorescence assays, dot blots and Western blots with NDV- and IDEs-specific antisera. All five IDEs showed good immunogenicity. IDE5 (328-342 aa) could recognize only class II NDV but did not react with the class I strain. Most of the IDEs are highly conserved among the different strains. A neutralization test in vitro showed that the peptide-specific mouse antisera of IDE4 (242-256 aa) and HN341-355, a reported neutralizing linear epitope, could partially neutralize avirulent LaSota as well as virulent strains at similar levels, suggesting that IDE4 might be a potential neutralizing linear epitope.

Conclusion: The HN protein is a major protective antigen of NDV that can induce neutralizing antibodies in animals. We identified five IDEs of the HN using a pepscan approach with NDV-specific chicken hyperimmune antisera. The five IDEs could elicit specific antibodies in mice. IDE4 (242-256 aa) was identified as a novel potential neutralizing linear epitope. These results will help elucidate the antigenic epitopes of the HN and facilitate the development of NDV vaccines.
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http://dx.doi.org/10.1186/s12985-020-01483-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789432PMC
January 2021

The investigation of detection and sensing mechanism of spicy substance based on human TRPV1 channel protein-cell membrane biosensor.

Biosens Bioelectron 2021 Jan 1;172:112779. Epub 2020 Nov 1.

School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address:

The transient receptor potential vanilloid 1 (TRPV1) is a key target for the spicy taste sensor and analgesic drug development. However, the human TRPV1-associated signaling remains to be obscure. In this study, we overexpressed human TRPV1 (hTRPV1) in HEK293T cells and explored its signaling activated by spicy substances. A cell membrane biosensor was constructed by using the cells highly expressed hTRPV1 through a layer-by-layer assembly. Our results showed that the activation constants by capsaicin, allicin and sanshool, the active components of chili pepper, garlic and mountain pepper, were K = 3.5206 × 10 mol/L, K = 5.0227 × 10 mol/L, K = 1.7832 × 10 mol/L. Obviously, the order of the sensitivity mediated by hTRPV1 was capsaicin > sanshool > allicin. The affinity values of the three spicy substances with hTRPV1 analyzed by molecular docking simulation also displayed the same law. Most importantly, some amide bonds and their similar groups and even benzene rings of spicy compounds were fund to be critical in the spicy sensing process. In addition, Glu570 in the active pocket of hTRPV1 plays an important role in identifying spicy substances. The elucidation of the detailed mechanism mediated by hTRPV1 in spicy sensing will lay a theoretical foundation to design rational strategies for screening of potential analgesics.
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http://dx.doi.org/10.1016/j.bios.2020.112779DOI Listing
January 2021

Fault Detection and Isolation Methods in Subsea Observation Networks.

Sensors (Basel) 2020 Sep 15;20(18). Epub 2020 Sep 15.

State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou 310027, China.

Subsea observation networks have gradually become the main means of deep-sea exploration. The reliability of the observation network is greatly affected by the severe undersea conditions. This study mainly focuses on theoretical research and the experimental platform verification of high-impedance and open-circuit fault detection for an underwater observation network. With the aid of deep learning, we perform the fault detection and prediction of the network operation. For the high-impedance and open-circuit fault detection of submarine cables, the entire system is modeled and simulated, and the voltage and current values of the operating nodes under different fault types are collected. Numerous calibrated data samples are supervised by a deep learning algorithm, and a fault location system model is built in the laboratory to verify the feasibility and superiority of the scheme. This paper also studies the fault isolation of the observation network, focusing on the communication protocol and the design of the fault isolation system. Experimental results verify the effectiveness of the proposed algorithm for the location and prediction of high-impedance and open-circuit faults, and the feasibility of the fault isolation system has also been verified. Moreover, the proposed methods greatly improve the reliability of undersea observation network systems.
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http://dx.doi.org/10.3390/s20185273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571193PMC
September 2020

Direct and indirect facilitation affect community productivity through changes in functional diversity in an alpine system.

Ann Bot 2021 01;127(2):241-249

State Key Laboratory of Grassland and Agro-ecosystems, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, China.

Background And Aims: Facilitation is an important ecological process for plant community structure and functional composition. Although direct facilitation has accrued most of the evidence so far, indirect facilitation is ubiquitous in nature and it has an enormous potential to explain community structuring. In this study, we assess the effect of direct and indirect facilitation on community productivity via taxonomic and functional diversity.

Methods: In an alpine community on the Tibetan Plateau, we manipulated the presence of the shrub Dasiphora fruticosa and graminoids in a fenced meadow and a grazed meadow to quantify the effects of direct and indirect facilitation. We measured four plant traits: height, lateral spread, specific leaf area (SLA) and leaf dry matter content (LDMC) of forbs; calculated two metrics of functional diversity [range of trait and community-weighted mean (CWM) of trait]; and assessed the responses of functional diversity to shrub facilitation. We used structural equation modelling to explore how shrubs directly and indirectly drove community productivity via taxonomic diversity and functional diversity.

Key Results: We found stronger effects from herbivore-mediated indirect facilitation than direct facilitation on productivity and taxonomic diversity, regardless of the presence of graminoids. For functional diversity, the range and CWM of height and SLA, rather than lateral spread and LDMC, generally increased due to direct and indirect facilitation. Moreover, we found that the range of traits played a primary role over taxonomic diversity and CWM of traits in terms of shrub effects on community productivity.

Conclusions: Our study reveals that the mechanism of shrub direct and indirect facilitation of community productivity in this alpine community is expanding the realized niche (i.e. expanding range of traits). Our findings indicate that facilitators might increase trait dispersion in the local community, which could alleviate the effect of environmental filters on trait values in harsh environments, thereby contributing to ecosystem functioning.
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http://dx.doi.org/10.1093/aob/mcaa170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789107PMC
January 2021

Application prospect of peptide-modified nano targeting drug delivery system combined with PD-1/PD-L1 based immune checkpoint blockade in glioblastoma.

Int J Pharm 2020 Nov 9;589:119865. Epub 2020 Sep 9.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.

Glioblastoma (GBM) is a type of primary malignant brain tumor with low median survival time, high recurrence rate and poor prognosis. The blood-brain barrier (BBB) and the diffuse infiltration of invasive GBM cells lead to a lower efficacy of traditional treatment. Recently, nanocarriers have become a promising method of brain drug delivery due to their ability to effectively cross the BBB. Especially, the peptide-modified nanocarriers can enhance the permeability, targeting and efficacy of chemotherapeutic agents against GBM. Moreover, the clinical application of immune checkpoint blockade (ICB) therapy in cancer treatment has attracted increasing attention, and the programmed death-1 receptor (PD-1) and PD-ligand-1 (PD-L1) monoclonal antibodies are considered to be a possible therapy for GBM. Consequently, we review the advances both in peptide-modified nano targeted drug delivery system and PD-1/PD-L1 based ICB in GBM treatment, and propose a new strategy combining the two methods, which may provide a novel approach for GBM treatment.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119865DOI Listing
November 2020

Identification of progranulin as a novel diagnostic biomarker for early-onset sepsis in neonates.

Eur J Clin Microbiol Infect Dis 2020 Dec 27;39(12):2405-2414. Epub 2020 Jul 27.

Department of Neonatology, Children's Hospital of Chongqing Medical University, 136 Zhongshan Road, Yuzhong District, Chongqing, 400014, China.

Neonatal early-onset sepsis (EOS) is associated with high morbidity and mortality. Accurate early diagnosis is crucial for prompt treatment and a better clinical outcome. We aimed to identify new biomarkers for the diagnosis of EOS. A total of 152 neonates with a risk of EOS were divided into an EOS group and a non-EOS group according to the conventional diagnostic criteria. Blood samples were collected within 0-24, 24-48, and 48-72 h after birth. Serum levels of progranulin (PGRN), interleukin (IL)-33, IL-17a, IL-23, IL-6, tumor necrosis factors α (TNF-α), interferon γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), procalcitonin (PCT), and C-reactive protein (CRP) were determined. PGRN levels were significantly elevated in the EOS neonates compared with the levels in the non-EOS neonates (1.53 vs. 0.77 ng/ml (median), P < 0.001), with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.76 (P < 0.001). Compared with PGRN, IL-33, IL-17a, IL-23, IL-6, PCT, and CRP showed significant (AUC > 0.70) but slightly less predictive power for EOS within the same time range. Stepwise multivariate regression analysis identified PGRN, IL-33, and PCT as independent predictors of EOS. In addition, the combined measurements of PGRN, IL-33, and PCT showed significantly higher predictive power for EOS than any of the three markers alone. PGRN showed greater efficacy for predicting EOS than the traditional markers PCT and CRP as well as other potential markers tested in this study. PGRN may serve as an effective biomarker for the early diagnosis of EOS.
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http://dx.doi.org/10.1007/s10096-020-03981-xDOI Listing
December 2020

The association between enteric viruses and necrotizing enterocolitis.

Eur J Pediatr 2021 Jan 22;180(1):225-232. Epub 2020 Jul 22.

Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

Studies on necrotizing enterocolitis (NEC) have not largely focused on enteric viruses. In order to demonstrate the association between enteric viruses and NEC, stool specimens of 51 neonates with NEC and 39 "normal" neonates were collected to detect rotavirus (RV), astrovirus (ASV), sapovirus, enterovirus (EV), adenovirus (ADV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human bocavirus (HBoV). Rotavirus A (RVA), ASV, EBV, and ADV were detected in both the NEC and control groups; however, EV and HBoV were detected only in the NEC group and CMV was not detected in either group. ASV was the most common enteric virus, but no significant differences were found between NEC and control groups, as was similarly the case for EBV and EV. The prevalence of ADV and HBoV was higher in the NEC group than in the control group (P = 0.011, P = 0.005, respectively) but RVA showed the opposite trend (P = 0.014). Virus positivity or negativity had no influence on the clinical manifestation of NEC.Conclusion: The roles of different viruses in NEC are not congruent. Some, such as ASV, may be regarded as commensal in neonates, while in NEC patients, the presence of ADV and EBV may be related to severity of disease. What is known: • The etiology of NEC remains unknown. Studies on necrotizing enterocolitis (NEC) have not largely focused on enteric viruses and the conclusions were inconsistent. What is new: • Enteric viruses are common in the gut of neonates, but not all of them are pathogenic. • The existence of ADV and EBV may be related to the severity of NEC.
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http://dx.doi.org/10.1007/s00431-020-03746-wDOI Listing
January 2021

Mechanism of the Intestinal Absorption of Six Flavonoids from Semen Across Caco-2 Cell Monolayer Model.

Curr Drug Metab 2020 ;21(8):633-645

Shijiazhuang Yiling pharmaceutical Co. Ltd, Hebei, 050035, China.

Background: Flavonoid compounds are one kind of active ingredients isolated from a traditional Chinese herb Zizyphi spinosae semen (ZSS). Studies have shown that ZSS flavonoids have significant antioxidant effects.

Methods: In this study, the Caco-2 cell monolayer model was constructed to investigate the intestinal absorption characteristics and mechanism of Isovitexin (IV), Swertisin (ST), Isovitexin-2''-O-β-D-glucopyranoside (IVG), Spinosin (S), 6'''-p-coumaroylspinosin (6-CS) and 6'''-feruloylspinosin (6-FS).

Results: The results of the bidirectional transport assay showed that the six flavonoids have good intestinal absorption in a near-neutral and 37°C environment, and the absorbability in descending order was 6-FS>6- CS>IVG>S>IV>ST. The results of carrier inhibition experiments and transport kinetics indicated that the absorption mechanism of six flavonoids was energy-dependent monocarboxylate transporter (MCT)-mediated active transport. In particular, the para-cellular pathway also participated in the transport of IV, ST, IVG and S. Furthermore, the efflux process of six flavonoids was mediated by P-glycoprotein (P-gp) and multidrug resistance protein (MRP), which may result in a decrease of bioavailability.

Conclusion: Our findings provide significant information for revealing the relationship between the intestinal absorption mechanism of flavonoids and its structure as well as laying a basis for the research of flavonoid preparations.
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http://dx.doi.org/10.2174/1389200221666200714100455DOI Listing
January 2020

15-Day subchronic developmental toxicity studies of ursolic acid in rats.

Food Chem Toxicol 2020 Oct 7;144:111537. Epub 2020 Jul 7.

Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia, 3168; iRiccorgpharm Health Pty Ltd, Melbourne, Australia, 3168. Electronic address:

Ursolic acid (UA) is a pentacyclic triterpenoid and has the characteristics to serve as a potential therapeutic agent for a range of disorders. However, detailed studies of the toxicity of UA, especially developmental toxicity of UA, are non-existing. The objective of this study was to determine the potential effects of UA on fetal development, adult reproductive system, and major organs. UA was dissolved in a 0.5% hydroxypropyl methylcellulose, 0.1% Tween 80 in Milli-Q Water solution. A 100, 300 or 1000 mg/kg/day dose of UA or a control vehicle was administered orally for 15 days to adults (Han Wistar) and pregnant females (Sprague-Dawley). The administration of UA in adults did not cause deaths or resulted in abnormal (reproductive) organ or body weights at the dose up to 1000 mg/kg/day. The administration of UA resulted in no significant toxicological changes in either maternal nor fetal subjects in terms of body weight, organ weights, food consumption, gross pathology, sex organs, maternal performances, and fetal performances. Together, this study indicates that oral dosing with UA is safe for adult rats and their offspring and the no observed adverse effect level for UA is likely higher than 1000 mg/kg/day.
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http://dx.doi.org/10.1016/j.fct.2020.111537DOI Listing
October 2020

Screening and mechanistic study of key sites of the hemagglutinin-neuraminidase protein related to the virulence of Newcastle disease virus.

Poult Sci 2020 Jul 4;99(7):3374-3384. Epub 2020 May 4.

College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi Province, China. Electronic address:

Newcastle disease is a kind of avian infectious disease caused by Newcastle disease virus (NDV). The virulence of NDV is dependent mainly on the fusion (F) protein and hemagglutinin-neuraminidase (HN) protein. The genomes of 2 viruses, NDV-Blackbird and NDV-Dove, are 99.9% similar, while NDV-Blackbird is a velogenic virus, and NDV-Dove is a lentogenic virus. Further analysis revealed that the F proteins of the 2 strains were identical, and only 5 amino acid sites on the HN proteins were inconsistent. Five different HN mutant plasmids were constructed and analyzed in this study. The results showed that the mutation F110L caused a significant increase in fusion-promotion activity caused by an increase in neuraminidase activity. Because of the increase in receptor-binding activity caused by G116R, there was a significant increase in fusion-promotion activity. The mutation G54S resulted in a slight decrease in the fusion-promotion activity caused by a slight decrease in receptor-binding activity. The slight increase in the fusion-promotion activity caused by A469V was associated with a significant increase in neuraminidase activity. Therefore, the amino acids L110 and R116 played a key role in determining the virulence difference between NDV-Blackbird and NDV-Dove, which could lay a foundation for illuminating the virulence differences of NDV strains, as well as the development of attenuated vaccines.
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http://dx.doi.org/10.1016/j.psj.2020.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597932PMC
July 2020

A Novel miRNA-hlo-miR-2-Serves as a Regulatory Factor That Controls Molting Events by Targeting CPR1 in Nymphs.

Front Microbiol 2020 29;11:1098. Epub 2020 May 29.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

Successful completion of the molting process requires new epidermal growth and ecdysis of the old cuticle in (). MicroRNAs (miRNAs) participate in the development of organisms by inhibiting the expression of their target mRNAs. In this study, a novel tick-specific miRNA was identified and denoted hlo-miR-2 that serves as a novel regulator of molting events in nymphs by targeting a cuticular protein. The full length of this cuticular protein was first obtained and named it CPR1. A qRT-PCR analysis showed that hlo-miR-2 and CPR1 exhibit significant tissue and temporal specificity and that their transcription levels are negatively correlated during the molting process. CPR1, as a direct target of hlo-miR-2, was identified by a luciferase reporter assay . Agomir treatment indicated that the overexpression of hlo-miR-2 significantly reduced the protein expression level of CPR1, decreased the molting rate and delayed the molting time point in nymphs. RNA interference (RNAi) experiments demonstrated that CPR1 was significantly associated with the molting process in nymphs. Phenotypic rescue experiments convincingly showed that hlo-miR-2 participated in molting events by targeting CPR1 in nymphs. In summary, we present evidence demonstrating that miRNAs constitute a novel important regulator of molting events in addition to hormones. The described functional evidence implicating CPR1 in molting events contributes to an improved understanding of the distinct functions of the CPR family in ticks and will aid the development of a promising application of cuticular protein RNAi in tick control.
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http://dx.doi.org/10.3389/fmicb.2020.01098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274079PMC
May 2020

Disentangling Large- and Small-Scale Abiotic and Biotic Factors Shaping Soil Microbial Communities in an Alpine Cushion Plant System.

Front Microbiol 2020 25;11:925. Epub 2020 May 25.

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, Lanzhou University, Lanzhou, China.

Microorganisms play a crucial role in biogeochemical cycles and ecosystem processes, but the key factors driving microbial community structure are poorly understood, particularly in alpine environments. In this study, we aim to disentangle the relative contribution of abiotic and biotic factors shaping bacterial and fungal community structure at large and small spatial and integration scales in an alpine system dominated by a stress-tolerant cushion species . These effects were assessed in two mountain ranges of northwest China and for two contrasting phenotypes of the cushion species inhabiting two different microtopographic positions. The large- and small-scale abiotic effects include the site and microhabitat effects, respectively, while the large- and small-scale biotic effects include the effects of cushion presence and cushion phenotype, respectively. Soil microbial communities were characterized by Illumina Miseq sequencing. Uni- and multivariate statistics were used to test the effects of abiotic and biotic factors at both scales. Results indicated that the site effect representing the soil pH and abiotic hydrothermal conditions mainly affected bacterial community structure, whereas fungal community structure was mainly affected by biotic factors with an equal contribution of cushion presence and cushion phenotype effects. Future studies should analyze the direct factors contributing to shaping microbial community structure in particular of the cushion phenotypes.
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http://dx.doi.org/10.3389/fmicb.2020.00925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262953PMC
May 2020

Ribosome Hibernation as a Stress Response of Bacteria.

Protein Pept Lett 2020 ;27(11):1082-1091

College of Life Sciences, Institute for Conservation and Utilization of Agro-Bioresources in Dabie Mountains, Xinyang Normal University, Xinyang 464000, China.

Ribosome is primarily regarded as the committing organelle for the translation process. Besides the expansion of its function from a translational machine for protein synthesis to a regulatory platform for protein quality control, the activity regulation and recycling of ribosome have been deepened significantly. Recent advances have confirmed a novel mechanism in the regulation of ribosome activity when a cell encounters adverse conditions. Due to the binding of certain protein factors onto a ribosome, the structural and functional change of the ribosome inside the cell will take place, thereby leading to the formation of inactive ribosomes (70S monomer or 100S dimer), or ribosome hibernation. By ribosome hibernation, the overall protein synthesis rate of a cell could be slowed down. The resistance to adverse conditions or chemicals of the host cell will be enhanced. In this paper, we discussed the phenomenon, molecular mechanism, and physiological effect of ribosome hibernation when cells are under stresses. And then, we discussed the resuscitation of a hibernating ribosome and the role of ribosome hibernation in the treatment of antimicrobial infection.
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http://dx.doi.org/10.2174/0929866527666200610142118DOI Listing
January 2021

Repeated dose (90 days) oral toxicity study of ursolic acid in Han-Wistar rats.

Toxicol Rep 2020 8;7:610-623. Epub 2020 May 8.

Department of Anatomy and Developmental Biology, Monash University, Melbourne, 3168, Australia.

Background: Ursolic acid (UA) has been used in alternative medicine for decades, and there has been a great interest in its medicinal properties. Despite this increased interest, a detailed long-term toxicity study has not been performed. The objective of this study was to determine the long-term toxic effect of UA on clinical chemistry, haematology, coagulation, pathology/morphology, behaviour and motor skills in rats.

Methods: A solution was made by dissolving UA in a mixture of 0.1% Tween 80 and 0.5% hydroxypropyl methylcellulose in Milli-Q Water. The control group received the vehicle, and the test groups received a dose up to 1000 mg/kg/day via oral gavage. The solution was administered to both male and female (Han-Wistar) rats for 90 consecutive days.

Results: UA did not cause any deaths, abnormal body weights or abnormal pathology at all test doses. In addition to that, no toxicological changes were observed in behaviour, neurotoxicity, coagulation, haematology or clinical chemistry that are related to the administration of UA.

Conclusion: This study indicates that oral dosing of UA for 90 consecutive days does not lead to toxic effects at any of the doses. Therefore, the NOAEL for UA is likely to be higher than 1000 mg/kg/day.
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http://dx.doi.org/10.1016/j.toxrep.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229404PMC
May 2020

Small design from big alignment: engineering proteins with multiple sequence alignment as the starting point.

Biotechnol Lett 2020 Aug 19;42(8):1305-1315. Epub 2020 May 19.

College of Physics and Electronic Engineering, Xinyang Normal University, Xinyang, 464000, China.

Multiple sequence alignment (MSA) is a fundamental way to gain information that cannot be obtained from the analysis of any individual sequence included in the alignment. It provides ways to investigate the relationship between sequence and function from a perspective of evolution. Thus, the MSA of proteins can be employed as a reference for protein engineering. In this paper, we reviewed the recent advances to highlight how protein engineering was benefited from the MSA of proteins. These methods include (1) engineering the thermostability or solubility of proteins by making it closer to the consensus sequence of the alignment through introducing site mutations; (2) structure-based engineering proteins with comparative modeling; (3) creating paleoenzymes featured with high thermostability and promiscuity by constructing the ancestral sequences derived from multiple sequence alignment; and (4) incorporating site-mutations targeting the evolutionarily coupled sites identified from multiple sequence alignment.
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http://dx.doi.org/10.1007/s10529-020-02914-0DOI Listing
August 2020

Dicaffeoyl polyamine derivatives from bitter goji: Contribution to the bitter taste of fruit.

Fitoterapia 2020 Jun 6;143:104543. Epub 2020 Mar 6.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address:

Although the bioactive compounds in goji have been thoroughly identified and quantified, little information is available on the bitter compounds in the berries, and no systematic works on the substances responsible for their bitterness have been performed. Herein, the substances contributing to the bitterness of berries were isolated and purified from bitter-tasting goji by the combined use of column chromatography and high-pressure liquid chromatography (HPLC). The bitterness of the isolated compounds was evaluated using a biosensor with immobilized rat taste-bud tissues. The structures were elucidated via comprehensive mass spectrometry (MS) and nuclear magnetic resonance (NMR) analyses. Seven spermine or spermidine alkaloids were identified, including four new compounds (lyciamarspermidines A and B and lyciamarspermines A and B). The intensities of the bitterness levels of the isolated compounds differed with the number of glucose substituents. These isolated compounds all contribute to the bitterness of goji. The results of this study provide opportunities for the further investigation of the bitterness of goji.
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http://dx.doi.org/10.1016/j.fitote.2020.104543DOI Listing
June 2020

Engineering the Translational Machinery for Biotechnology Applications.

Mol Biotechnol 2020 Apr;62(4):219-227

College of Life Sciences, and Institute for Conservation and Utilization of Agro-Bioresources in Dabie Mountains, Xinyang Normal University, Xinyang, 464000, China.

The ribosome is an essential organelle in charge of the translational processes in all kinds of cells. Currently, the scenario of its function has been significantly expanded from the classic machine for protein synthesis to a regulatory platform for quality control to maintain the protein homeostasis in a living cell. The ribosome is much more than a mechanical device with a static structure: it is inherently dynamic in structure and function, especially in response to the environmental fluctuations. Considerable effort has been made to regulate its structure and physiological function by engineering the components of a ribosome. The findings of the pioneering studies significantly deepened our understanding of a ribosome and exemplified how a ribosome could be engineered for biotechnology purposes in the era of synthetic biology. The engineering of ribosome offered highly accessible methods capable of comprehensively optimizing the performance of strains of industrial importance. In this article, the relevant recent advances were systematically reviewed.
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http://dx.doi.org/10.1007/s12033-020-00246-yDOI Listing
April 2020

Sensitive detection of low-concentration sulfide based on the synergistic effect of rGO, np-Au, and recombinant microbial cell.

Biosens Bioelectron 2020 Mar 26;151:111985. Epub 2019 Dec 26.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, PR China. Electronic address:

With the aggravation of sulfide pollution, more and more attention has been paid to the detection of sulfide in the environment. However, the detection of low-concentration sulfide is still a technical bottleneck to be solved urgently. In this study, a synergistic effect strategy that combines the co-catalysis of nanoporous gold (np-Au) and recombinant microbial cell with the excellent electrical conductivity of reduced graphene oxide (rGO) was proposed for the sensitive detection of low-concentration sulfide. A rGO/np-Au composite was fabricated and then used as an immobilization support for the bio-recognition element of recombinant Escherichia coli (E. coli) over-expressed sulfide: quinone oxidoreductase (SQR). A microbial biosensor (E. coli/rGO/np-Au/GCE) was successfully constructed for the sensitive detection of low-concentration sulfide. Due to the synergistic effect of rGO, np-Au, and E. coli cells, the sensitivity of the proposed microbial biosensor towards sulfide reached 400.42 μA mM cm with a wide linear response ranging from 100 nM to 7 mM, as well as a low detection limit of 98.5 nM using amperometric i-t curve method. Furthermore, the microbial biosensor was successfully applied to the detection of sulfide in wastewater with strong anti-interference ability, high reproducibility, and strong stability. These results confirmed that the proposed microbial biosensor was ideal for the detection of low-concentration sulfide in a reliable, specific, and sensitive way.
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http://dx.doi.org/10.1016/j.bios.2019.111985DOI Listing
March 2020

Establishment of long-term serum-free culture for lacrimal gland stem cells aiming at lacrimal gland repair.

Authors:
Sa Xiao Yan Zhang

Stem Cell Res Ther 2020 01 8;11(1):20. Epub 2020 Jan 8.

MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, Guangdong, People's Republic of China.

Background: Aqueous-deficient dry eye disease (ADDED) resulting from dysfunction of the lacrimal gland (LG) is currently incurable. Although LG stem/progenitor cell-based therapy is considered to be a promising strategy for ADDED patients, the lack of a reliable serum-free culture method to obtain enough lacrimal gland stem cells (LGSCs) and the basic standard of LGSC transplantation are obstacles for further research.

Methods: Adult mouse LGSCs were cultured in Matrigel-based 3D culture under serum-free culture condition, which contained EGF, FGF10, Wnt3A, and Y-27632. LGSCs were continuously passaged over 40 times every 7 days, and the morphology and cell numbers were recorded. LGSCs were induced to differentiate to ductal cells by reducing Matrigel rigidity, while fetal bovine serum was used for the induction of acinar cells. RT-PCR or qRT-PCR analysis, RNA-sequence analysis, H&E staining, and immunofluorescence were used for characterization and examining the differentiation of LGSCs. LGSCs were allotransplanted into diseased LGs to examine the ability of repairing the damage. The condition of eye orbits was recorded using a camera, the tear production was measured using phenol red-impregnated cotton threads, and the engraftments of LGSCs were examined by immunohistochemistry.

Results: We established an efficient 3D serum-free culture for adult mouse LGSCs, in which LGSCs could be continuously passaged for long-term expansion. LGSCs cultured from both the healthy and ADDED mouse LGs expressed stem/progenitor cell markers Krt14, Krt5, P63, and nestin, had the potential to differentiate into acinar or ductal-like cells in vitro and could engraft into diseased LGs and relieve symptoms of ADDED after orthotopic injection of LGSCs.

Conclusion: We successfully established an efficient serum-free culture for adult mouse LGSCs aiming at LG repair for the first time. Our approach provides an excellent theoretical and technical reference for future clinical research for ADDED stem cell therapy.
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http://dx.doi.org/10.1186/s13287-019-1541-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951017PMC
January 2020
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