Publications by authors named "Xiang Shi"

124 Publications

Five distinct fucan sulfates from sea cucumber Pattalus mollis: Purification, structural characterization and anticoagulant activities.

Int J Biol Macromol 2021 Jul 9;186:535-543. Epub 2021 Jul 9.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China. Electronic address:

Fucan sulfates from echinoderm possess characteristic structures and various biological activities. Herein, comprehensive methods including enzymolysis, ion-exchange chromatography and size exclusion chromatography lead to the purification of five fucan sulfates (FSI, FSII, FSIII, FSIV, FSV) from the sea cucumber Pattalus mollis. Chemical composition analysis showed that they were all composed of l-fucose. Their sulfate content was determined by a conductimetric method. The molecular weight (Mw) of FSI, FSII, FSIII, FSIV and FSV were measured as 238.3 kDa, 81.0 kDa, 82.0 kDa, 23.2 kDa and 6.12 kDa, respectively. Detailed NMR spectroscopic analysis revealed that the structural sequence of FSI and FSII was →3)-l-Fuc-α(1→, where Fuc were Fuc (10%), Fuc (44%), Fuc (10%), Fuc (36%), that of FSIII was →4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → 4)-l-Fuc-(α1→, where Fuc and Fuc were in equal molar, and that FSIV was →4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → 4)-l-Fuc-(α1→4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → . This is the first report that such a diversity of fucan sulfates were obtained from the same sea cucumber species. Biological activity showed that FSI, FSII, FSIII and FSIV exhibited potent anticoagulant by prolonging the APTT. Among them, FSII, FSIII and FSIV showed the similar potency, while FSI owned the strongest. Structure-activity relationships analysis showed that molecular weight and sulfation degree should be the crucial factors for the activity.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.049DOI Listing
July 2021

I Understand You: Blind 3D Human Attention Inference From the Perspective of Third-Person.

IEEE Trans Image Process 2021 9;30:6212-6225. Epub 2021 Jul 9.

Inferring object-wise human attention in 3D space from the third-person perspective (e.g., a camera) is crucial to many visual tasks and applications, including human-robot collaboration, unmanned vehicle driving, etc. Challenges arise from classical human attention when human eyes are not visible to cameras, gaze point is outside the field of vision, or the gazed object is occluded by others in the 3D space. In this case, blind 3D human attention inference brings a new paradigm to the community. In this paper, we address these challenges by proposing a scene-behavior associated mechanism, in which both 3D scene and temporal behavior of human are adopted to infer object-wise human attention and its transition. Specifically, point cloud is reconstructed and used for the spatial representation of 3D scene, which is beneficial to handle the blind problem from the perspective of a camera. Based on this, in order to address the blind human attention inference without eye information, we propose a Sequential Skeleton Based Attention Network (SBAN) for behavior-based attention modeling. As is embedded in the scene-behavior associated mechanism, the proposed SBAN is built under the temporal architecture of Long-Short-Term-Memory (LSTM). Our network employs human skeleton as behavior representation, and maps it to the attention direction frame by frame, which makes attention inference a temporal-correlated issue. With the help of SBAN, 3D gaze spot and further the attended objects can be obtained frame by frame via intersection and segmentation on the previously reconstructed point cloud. Finally, we conduct experiments from various aspects to verify the object-wise attention localization accuracy, the angular error of attention direction calculation, as well as the subjective results. The experimental results show that the proposed outperforms other competitors.
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http://dx.doi.org/10.1109/TIP.2021.3092842DOI Listing
July 2021

I Understand You: Blind 3D Human Attention Inference From the Perspective of Third-Person.

IEEE Trans Image Process 2021 9;30:6212-6225. Epub 2021 Jul 9.

Inferring object-wise human attention in 3D space from the third-person perspective (e.g., a camera) is crucial to many visual tasks and applications, including human-robot collaboration, unmanned vehicle driving, etc. Challenges arise from classical human attention when human eyes are not visible to cameras, gaze point is outside the field of vision, or the gazed object is occluded by others in the 3D space. In this case, blind 3D human attention inference brings a new paradigm to the community. In this paper, we address these challenges by proposing a scene-behavior associated mechanism, in which both 3D scene and temporal behavior of human are adopted to infer object-wise human attention and its transition. Specifically, point cloud is reconstructed and used for the spatial representation of 3D scene, which is beneficial to handle the blind problem from the perspective of a camera. Based on this, in order to address the blind human attention inference without eye information, we propose a Sequential Skeleton Based Attention Network (SBAN) for behavior-based attention modeling. As is embedded in the scene-behavior associated mechanism, the proposed SBAN is built under the temporal architecture of Long-Short-Term-Memory (LSTM). Our network employs human skeleton as behavior representation, and maps it to the attention direction frame by frame, which makes attention inference a temporal-correlated issue. With the help of SBAN, 3D gaze spot and further the attended objects can be obtained frame by frame via intersection and segmentation on the previously reconstructed point cloud. Finally, we conduct experiments from various aspects to verify the object-wise attention localization accuracy, the angular error of attention direction calculation, as well as the subjective results. The experimental results show that the proposed outperforms other competitors.
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http://dx.doi.org/10.1109/TIP.2021.3092842DOI Listing
July 2021

Long-term biocide efficacy and its effect on a souring microbial community.

Appl Environ Microbiol 2021 Jun 23:AEM0084221. Epub 2021 Jun 23.

The Lyell Centre, Heriot-Watt University, Edinburgh, UK.

Reservoir souring, which is the production of HS mainly by sulfate-reducing microorganisms (SRM) in oil reservoirs, has been a long-standing issue for the oil industry. While biocides have been frequently applied to control biogenic souring, the effects of biocide treatment are usually temporary, and biocides eventually fail. The reasons behind biocide failure and the long-term response of the microbial community remain poorly understood. In this study, one time biocide treatments with glutaraldehyde (GA) and an aldehyde-releasing biocide (ARB) at low (100 ppm) and high (750 ppm) dosages were individually applied to a complex sulfate-reducing microbial community, followed by one-year monitoring of the chemical responses and the microbial community succession. The chemical results showed that souring control failed after 7 days at 100 ppm dosage regardless the biocide type, and that lasting souring control for the entire one-year timespan was only achieved with ARB at 750 ppm. Microbial community analyses suggested that the high dosage biocide treatments resulted in one order of magnitude lower average total microbial abundance and average SRM abundance compared to the low dosage treatments. The recurrence of souring was associated with reduction of alpha diversity and with long-term microbial community structure change, thus monitoring changes in microbial community metrics may serve as early warnings of the failure of a biocide-based souring control programme in the field. Furthermore, spore-forming sulfate reducers ( and ) were enriched and became dominant in both GA-treated groups, which could cause challenges to the design of long-lasting remedial souring control strategies. Reservoir souring is a detrimental problem for the oil and gas industry as HS corrodes the steel infrastructure, downgrades the oil quality and poses substantial risks to the field personnel and the environment. Biocides have been widely applied to remedy souring, yet the long-term performance of biocide treatments is hard to predict or optimise due to limited understanding of the microbial ecology affected by biocide treatment. This study investigates the long-term biocide performance and associated changes in the abundance, diversity and structure of the souring microbial community, thus advancing the knowledge towards a deeper understanding of the microbial ecology of biocide-treated systems, and contributing to the improvement of current biocide-based souring control practices. The study showcases the potential application of incorporating microbial community analyses to forecast souring and highlights the long-term consequences of the biocide treatment on the microbial communities, with relevance to both operators and regulators.
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http://dx.doi.org/10.1128/AEM.00842-21DOI Listing
June 2021

Association of T2285C polymorphism in PARP1 gene coding region with its expression, activity and NSCLC risk along with prognosis.

Mutagenesis 2021 Jun 16. Epub 2021 Jun 16.

Emergency Center, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

Poly (ADP-ribose) polymerase-1(PARP1), a DNA repair gene, is the crucial player in the maintenance of genome integrity. T2285C polymorphism in coding region of PARP1 has been reported to be associated with susceptibility to tumors. We explored the relation and mechanism of T2285C polymorphism of PARP1 to its expression and activity along with risk and prognosis in NSCLC. mRNA expression was measured using qRT-PCR assay or collected from TCGA dataset. Protein expression was examined with immunoblotting assay. Genotypes were determined by PCR-RFLP and sequencing approaches. PARP1 activity was determined with enzyme activity assay. Regulation of SIRT7 to PARP1 were determined by over-expression and small interference experiment. Association of PARP1 T2285C polymorphism with NSCLC risk was evaluated via multiple logistic regression analysis. Comparison of treatment response and PFS of NSCLC patients among different genotypes or regimens was made by Chi-square test. Results indicated that mRNA and protein expression of PARP1 dramatically increased in NSCLC tissues in comparison to paired para-carcinoma tissues (P<0.05). TC/CC mutant genotypes were associated with markedly enhanced PARP1 mRNA level compared with TT genotype (P=0.011). No significant difference was discovered in PARP1 protein expression among TT, TC or CC genotypes (P>0.05). Subjects with variant allele C had higher risk of NSCLC in comparison to allele T carriers [odds ratio (OR) =1.560; P=0.000]. NSCLC patients carrying mutational TC or CC genotypes were correlated with unfavorable response to platinum-based chemotherapy (TT vs.TC vs.CC, P=0.010), and shorter PFS compared to TT genotype (TT vs.TC vs.CC, P=0.009). T2285C mutation of PARP1 resulted in the enhancement of its mRNA, but the decrease of enzyme activity in tumor cell. Overexpression of SIRT7 attenuated PARP1 expression and activity. These findings suggest the variant allele C of T2285C polymorphism of PARP1 linked to an increase of NSCLC risk, and unfavorable efficacy and prognosis of NSCLC patients with platinum-based chemotherapy, which might be associated with enhancement of its mRNA expression and the diminishment of activity. Identification of PARP1 T2285C polymorphism and mRNA expression may be the promising way for the individualized treatment of NSCLC.
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http://dx.doi.org/10.1093/mutage/geab022DOI Listing
June 2021

Production of viable chicken by allogeneic transplantation of primordial germ cells induced from somatic cells.

Nat Commun 2021 05 20;12(1):2989. Epub 2021 May 20.

Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

The allogeneic transplantation of primordial germ cells (PGCs) derived from somatic cells overcomes the limitation of avian cloning. Here, we transdifferentiate chicken embryo fibroblasts (CEFs) from black feathered Langshan chickens to PGCs and transplant them into White Plymouth Rock chicken embryos to produce viable offspring with characteristics inherited from the donor. We express Oct4/Sox2/Nanog/Lin28A (OSNL) to reprogram CEFs to induced pluripotent stem cells (iPSCs), which are further induced to differentiate into PGCs by BMP4/BMP8b/EGF. DNA demethylation, histone acetylation and glycolytic activation elevate the iPSC induction efficiency, while histone acetylation and glycolytic inhibition facilitate PGCs formation. The induced PGCs (iPGCs) are transplanted into the recipients, which are self-crossed to produce 189/509 somatic cells derived chicken with the donor's characteristics. Microsatellite analysis and genome sequencing confirm the inheritance of genetic information from the donor. Thus, we demonstrate the feasibility of avian cloning from somatic cells.
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http://dx.doi.org/10.1038/s41467-021-23242-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138025PMC
May 2021

Effects of a Soft Robotic Hand for Hand Rehabilitation in Chronic Stroke Survivors.

J Stroke Cerebrovasc Dis 2021 Jul 22;30(7):105812. Epub 2021 Apr 22.

Department of Biomedical Engineering, the Chinese University of Hong Kong, Hong Kong. Electronic address:

Objectives: Soft robotic hands are proposed for stroke rehabilitation in terms of their high compliance and low inherent stiffness. We investigated the clinical efficacy of a soft robotic hand that could actively flex and extend the fingers in chronic stroke subjects with different levels of spasticity.

Methods: Sixteen chronic stroke subjects were recruited into this single-group study. Subjects underwent 20 sessions of 1-hour EMG-driven soft robotic hand training. Training effect was evaluated by the pre-training and post-training assessments with the clinical scores: Action Research Arm Test(ARAT), Fugl-Meyer Assessment for Upper Extremity(FMA-UE), Box-and-Block test(BBT), Modified Ashworth Scale(MAS), and maximum voluntary grip strength.

Results: For all the recruited subjects (n = 16), significant improvement of upper limb function was generally observed in ARAT (increased mean=2.44, P = 0.032), FMA-UE (increased mean=3.31, P = 0.003), BBT (increased mean=1.81, P = 0.024), and maximum voluntary grip strength (increased mean=2.14 kg, P < 0.001). No significant change was observed in terms of spasticity with the MAS (decreased mean=0.11, P = 0.423). Further analysis showed subjects with mild or no finger flexor spasticity (MAS<2, n = 9) at pre-training had significant improvement of upper limb function after 20 sessions of training. However, for subjects with moderate and severe finger flexor spasticity (MAS=2,3, n = 7) at pre-training, no significant change in clinical scores was shown and only maximum voluntary grip strength had significant increase.

Conclusion: EMG-driven rehabilitation training using the soft robotic hand with flexion and extension could be effective for the functional recovery of upper limb in chronic stroke subjects with mild or no spasticity.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105812DOI Listing
July 2021

Carbon nitride/positive carbon black anchoring PtNPs assembled by-rays as ORR catalyst with excellent stability.

Nanotechnology 2021 May 31;32(34). Epub 2021 May 31.

State Key Laboratory of Separation Membranes and Membrane Processes, School of Textile Science and Engineering, Tiangong University, Tianjin 300387, People's Republic of China.

Electrocatalytic performance of low-cost graphitic carbon nitride (CN) is greatly limited by its limited conductivity and small specific surface area. Herein, a simple and cost-effective idea to produce novel nanocomposite is constructed by the CN and cetyl trimethyl ammonium bromide functionalized carbon black (CB) anchored platinum nanoparticles as highly efficient oxygen reduction catalysts based on gamma irradiation. The assembled carbon nitride/positive carbon black anchoring PtNPs (Pt/CN-CB) catalyst exhibits significantly improved specific surface area, high graphitization, and uniformly dispersed ultra-small platinum nanoparticles. For the oxygen reduction reaction (ORR) performance, the catalyst shows more positive onset-potential (0.93 V versus RHE) and larger diffusion limiting current density (5.65 mA cm) compared with benchmark Pt/C catalysts in alkaline medium. Moreover, the Pt/CN-CBcatalyst exhibits a small Tafel slope (92 mV dec). Besides, the catalyst was demonstrated the remarkable methanol tolerance and good long-term stability under working conditions. This work provides a new and effective-rays irradiation for synthesizing the carbon nitride catalysts for energy conversion and storage applications.
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http://dx.doi.org/10.1088/1361-6528/abfabeDOI Listing
May 2021

Cascade diversification directs generation of neuronal diversity in the hypothalamus.

Cell Stem Cell 2021 Apr 17. Epub 2021 Apr 17.

State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200031, China; Chinese Institute for Brain Research, Beijing 102206, China. Electronic address:

The hypothalamus contains an astounding heterogeneity of neurons that regulate endocrine, autonomic, and behavioral functions. However, its molecular developmental trajectory and origin of neuronal diversity remain unclear. Here, we profile the transcriptome of 43,261 cells derived from Rax hypothalamic neuroepithelium to map the developmental landscape of the mouse hypothalamus and trajectory of radial glial cells (RGCs), intermediate progenitor cells (IPCs), nascent neurons, and peptidergic neurons. We show that RGCs adopt a conserved strategy for multipotential differentiation but generate Ascl1 and Neurog2 IPCs. Ascl1 IPCs differ from their telencephalic counterpart by displaying fate bifurcation, and postmitotic nascent neurons resolve into multiple peptidergic neuronal subtypes. Clonal analysis further demonstrates that single RGCs can produce multiple neuronal subtypes. Our study reveals that multiple cell types along the lineage hierarchy contribute to fate diversification of hypothalamic neurons in a stepwise fashion, suggesting a cascade diversification model that deconstructs the origin of neuronal diversity.
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http://dx.doi.org/10.1016/j.stem.2021.03.020DOI Listing
April 2021

Structural Characterization and Heparanase Inhibitory Activity of Fucosylated Glycosaminoglycan from .

Mar Drugs 2021 Mar 18;19(3). Epub 2021 Mar 18.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China.

Unique fucosylated glycosaminoglycans (FG) have attracted increasing attention for various bioactivities. However, the precise structures of FGs usually vary in a species-specific manner. In this study, HfFG was isolated from and purified by anion exchange chromatography with the yield of ~0.9%. HfFG was composed of GlcA, GalNAc and Fuc, its molecular weight was 47.3 kDa, and the -OSO/-COO molar ratio was 3.756. HfFG was depolymerized by a partial deacetylation-deaminative cleavage method to obtain the low-molecular-weight HfFG (dHfFG). Three oligosaccharide fragments (Fr-1, Fr-2, Fr-3) with different molecular weights were isolated from the dHfFG, and their structures were revealed by 1D and 2D NMR spectroscopy. HfFG should be composed of repeating trisaccharide units -{(L-FucS-α1,3-)d-GlcA-β1,3-d-GalNAc-β1,4-}-, in which sulfated fucose (FucS) includes Fuc, Fuc and Fuc residues linked to O-3 of GlcA in a ratio of 45:35:20. Furthermore, the heparanase inhibitory activities of native HfFG and oligosaccharide fragments (Fr-1, Fr-2, Fr-3) were evaluated. The native HfFG and its oligosaccharides exhibited heparanase inhibitory activities, and the activities increased with the increase of molecular weight. Additionally, structural characteristics such as sulfation patterns, the terminal structure of oligosaccharides and the presence of fucosyl branches may be important factors affecting heparanase inhibiting activity.
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http://dx.doi.org/10.3390/md19030162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003118PMC
March 2021

Inhibition of TLR4 signaling protects mice from sensory and motor dysfunction in an animal model of autoimmune peripheral neuropathy.

J Neuroinflammation 2021 Mar 22;18(1):77. Epub 2021 Mar 22.

The Alan Edwards Centre for Research on Pain, McGill University, 740 Docteur Penfield Ave, Suite 3200C, Montreal, QC, H3A0G1, Canada.

Background: While the etiology remains elusive, macrophages and T cells in peripheral nerves are considered as effector cells mediating autoimmune peripheral neuropathy (APN), such as Guillain-Barre syndrome. By recognizing both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) signals, TLRs play a central role in the initiation of both innate and adaptive immune responses. In this study, we aimed to understand the involvement of TLR4 in the pathogenesis of APN and explore the potential of TLR4 as a drug target for therapeutic use.

Methods: APN was induced by a partial ligation on one of the sciatic nerves in B7.2 (L31) transgenic mice which possess a predisposed inflammatory background. APN pathology and neurological function were evaluated on the other non-injured sciatic nerve.

Results: TLR4 and its endogenous ligand HMGB1 were highly expressed in L31 mice, in circulating immune cells and in peripheral nerves. Enhanced TLR4 signaling was blocked with TAK 242, a selective TLR4 inhibitor, before and after disease onset. Intraperitoneal administration of TAK 242 not only inhibited monocyte, macrophage and CD8 T cell activation, but also reduced the release of pro-inflammatory cytokines. TAK 242 protected mice from severe myelin and axonal loss, resulting in a remarkable improvement in mouse motor and sensory functions. TAK 242 was effective in alleviating the disease in both preventive and reversal paradigms.

Conclusion: The study identified the critical contribution of TLR4-mediated macrophage activation in disease course and provided strong evidence to support TLR4 as a useful drug target for treating inflammatory autoimmune neuropathy.
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http://dx.doi.org/10.1186/s12974-021-02126-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983271PMC
March 2021

Large-area display textiles integrated with functional systems.

Nature 2021 03 10;591(7849):240-245. Epub 2021 Mar 10.

State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China.

Displays are basic building blocks of modern electronics. Integrating displays into textiles offers exciting opportunities for smart electronic textiles-the ultimate goal of wearable technology, poised to change the way in which we interact with electronic devices. Display textiles serve to bridge human-machine interactions, offering, for instance, a real-time communication tool for individuals with voice or speech difficulties. Electronic textiles capable of communicating, sensing and supplying electricity have been reported previously. However, textiles with functional, large-area displays have not yet been achieved, because it is challenging to obtain small illuminating units that are both durable and easy to assemble over a wide area. Here we report a 6-metre-long, 25-centimetre-wide display textile containing 5 × 10 electroluminescent units spaced approximately 800 micrometres apart. Weaving conductive weft and luminescent warp fibres forms micrometre-scale electroluminescent units at the weft-warp contact points. The brightness between electroluminescent units deviates by less than 8 per cent and remains stable even when the textile is bent, stretched or pressed. Our display textile is flexible and breathable and withstands repeated machine-washing, making it suitable for practical applications. We show that an integrated textile system consisting of display, keyboard and power supply can serve as a communication tool, demonstrating the system's potential within the 'internet of things' in various areas, including healthcare. Our approach unifies the fabrication and function of electronic devices with textiles, and we expect that woven-fibre materials will shape the next generation of electronics.
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http://dx.doi.org/10.1038/s41586-021-03295-8DOI Listing
March 2021

Spin1z induces the male pathway in the chicken by down-regulating Tcf4.

Gene 2021 May 22;780:145521. Epub 2021 Feb 22.

Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China. Electronic address:

SPINDLIN1-Z (SPIN1Z), a member of the Spin/Ssty(Y-linked spermiogenesis specific transcript) protein family, participates in the early embryonic development process. Our previous RNA-seq analysis indicates that the level of Spin1z was abundantly expressed in male embryonic stem cells (ESCs) and primitive germ cells (PGCs), we speculate that Spin1z may play an important role in chicken male differentiation. Therefore, the loss- and gain-of-function experiments provide solid evidence that Spin1z is both necessary and sufficient to initiate male development in chicken. Furthermore, chromatin immunoprecipitation (ChIP) assay and the dual-luciferase assay was performed to further confirm that Spin1z contributed to chicken male differentiation by inhibiting the Tcf4 transcription. Our findings provide a novel insight into the molecular mechanism for chicken male differentiation.
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http://dx.doi.org/10.1016/j.gene.2021.145521DOI Listing
May 2021

Glycolysis Combined with Core Pluripotency Factors to Promote the Formation of Chicken Induced Pluripotent Stem Cells.

Animals (Basel) 2021 Feb 6;11(2). Epub 2021 Feb 6.

Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) in vitro. Previously, a lentivirus induction strategy of introducing Oct4, Sox2, Nanog and Lin28 (OSNL) into the iPSC process has been shown as a possible way to produce chicken iPSCs from chicken embryonic fibroblasts, but the induction efficiency of this method was found to be significantly limiting. In order to help resolve this efficiency obstacle, this study seeks to clarify the associated regulation mechanisms and optimizes the reprogramming strategy of chicken iPSCs. This study showed that glycolysis and the expression of glycolysis-related genes correlate with a more efficient reprogramming process. At the same time, the transcription factors Oct4, Sox2 and Nanog were found to activate the expression of glycolysis-related genes. In addition, we introduced two small-molecule inhibitors (2i-SP) as a "glycolysis activator" together with the OSNL cocktail, and found that this significantly improved the induction efficiency of the iPSC process. As such, the study identifies direct molecular connections between core pluripotency factors and glycolysis during the chicken iPSC induction process and, with its results, provides a theoretical basis and technical support for chicken somatic reprogramming.
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http://dx.doi.org/10.3390/ani11020425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915628PMC
February 2021

promotes chicken female differentiation by inhibiting .

Cytotechnology 2021 Feb 2;73(1):101-113. Epub 2021 Jan 2.

College of Animal Science and Technology, Jiangsu Province Key Laboratory of Animal Breeding and Molecular Design, Yangzhou University, 88 South University Ave, Yangzhou, 225009 Jiangsu China.

The sex determination and control of poultry is a key problem in production and scientific research despite few studies on regulatory factors, especially transcription factors in sex determination. In the early stage of this study, high-throughput sequencing was used to screen the differentially expressed gene in male and female embryonic stem cells (ESCs) and primordial germ cells (PGCs). The qRT-PCR discovered that the JUN gene significantly increased from embryonic days (E) 2.5 later in chicken embryo development, and the female gonad expression was much higher than that of the male after E14.5. Lentivirus shRNA, shRNA- interference, and OE- overexpression vectors were successfully constructed. After interfering with in vivo, male characteristics appeared in ZW embryonic gonads at E18.5. Meanwhile, the male-specific genes and were upregulated, the female-specific genes and were downregulated, and the estradiol in the gonads was significantly decreased. The situation was reversed after the overexpression of , ZZ chicken embryo developed into female sexual characteristics. The double luciferase report has found that the promoter activity was significantly upregulated after interference with , and significantly increased after the deletion of the binding site. After the injection of the -shRNA vector into the blood vessel in vivo, it was discovered that and of ZW embryos at E18.5 were downregulated, and were significantly upregulated, and the gonads show femininity. In conclusion, this study proves that is a key regulator in the process of chicken female sex differentiation, which can inhibit the transcription of and promote the synthesis of estradiol, and participate in the process of chicken sex differentiation. This study lays a foundation for the analysis of the molecular mechanism of chicken sex determination and the development of poultry sex control technology.
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http://dx.doi.org/10.1007/s10616-020-00447-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817717PMC
February 2021

Verification of Finger Joint Stiffness Estimation Method With Soft Robotic Actuator.

Front Bioeng Biotechnol 2020 18;8:592637. Epub 2020 Dec 18.

Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong.

Stroke has been the leading cause of disability due to the induced spasticity in the upper extremity. The constant flexion of spastic fingers following stroke has not been well described. Accurate measurements for joint stiffness help clinicians have a better access to the level of impairment after stroke. Previously, we conducted a method for quantifying the passive finger joint stiffness based on the pressure-angle relationship between the spastic fingers and the soft-elastic composite actuator (SECA). However, it lacks a ground-truth to demonstrate the compatibility between the SECA-facilitated stiffness estimation and standard joint stiffness quantification procedure. In this study, we compare the passive metacarpophalangeal (MCP) joint stiffness measured using the SECA with the results from our designed standalone mechatronics device, which measures the passive metacarpophalangeal joint torque and angle during passive finger rotation. Results obtained from the fitting model that concludes the stiffness characteristic are further compared with the results obtained from SECA-Finger model, as well as the clinical score of Modified Ashworth Scale (MAS) for grading spasticity. These findings suggest the possibility of passive MCP joint stiffness quantification using the soft robotic actuator during the performance of different tasks in hand rehabilitation.
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http://dx.doi.org/10.3389/fbioe.2020.592637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775510PMC
December 2020

Apelin-13 induces mitophagy in bone marrow mesenchymal stem cells to suppress intracellular oxidative stress and ameliorate osteoporosis by activation of AMPK signaling pathway.

Free Radic Biol Med 2021 02 30;163:356-368. Epub 2020 Dec 30.

Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang, China. Electronic address:

Osteoporosis is characterized by impaired bone metabolism. Current estimates show that it affects millions of people worldwide and causes a serious socioeconomic burden. Mitophagy plays key roles in bone marrow mesenchymal stem cells (BMSCs) osteoblastic differentiation, mineralization, and survival. Apelin is an endogenous adipokine that participates in bone homeostasis. This study was performed to determine the role of Apelin in the osteoporosis process and whether it affects mitophagy, survival, and osteogenic capacity of BMSCs in in vitro and in vivo models of osteoporosis. Our results demonstrated that Apelin was down-regulated in ovariectomized-induced osteoporosis rats and Apelin-13 treatment activated mitophagy in BMSCs, ameliorating oxidative stress and thereby reviving osteogenic function via AMPK-α phosphorylation. Besides, Apelin-13 administration restored bone mass and microstructure as well as reinstated mitophagy, enhanced osteogenic function in OVX rats. Collectively, our findings reveal the intrinsic mechanisms underlying Apelin-13 regulation in BMSCs and its potential therapeutic values in the treatment of osteoporosis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.235DOI Listing
February 2021

River water intrusion as a source of inflow into the sanitary sewer system.

Water Sci Technol 2020 Dec;82(11):2472-2481

Power Construction Corporation of China, Hangzhou, China, 310014.

Previous studies on the extraneous water problem (or infiltration/inflow) in sanitary sewer systems assumed that the wastewater flow is mainly composed of foul sewage (FS), groundwater infiltration (GWI) and rainfall-derived inflow and infiltration (RDII). Most existing assessment methods are based on this assumption. In 2018, China initiated the 'Protection of the Yangtze River Program', and the two-year research data showed that it was neither the GWI nor the RDII but the direct surface water intrusion (DSWI), which has rarely been reported in literatures, that serves as the main source of the extraneous water in many local sewer systems. The discovery has enriched the understanding of the extraneous water in sewer systems. Meanwhile, it brings new challenges for the assessment of extraneous water. In this study, starting from the analysis of the low influent concentration of chemical oxygen demand (COD) of the wastewater treatment plant in a southeastern city in China, a river water intrusion point was successfully localized and the volume of river water intrusion was quantified by a series of field experiments. The methodology used in this study can also be applied in other areas with DSWI.
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http://dx.doi.org/10.2166/wst.2020.516DOI Listing
December 2020

Risk factors for postpartum depression in Chinese women: A cross-sectional study at 6 weeks postpartum.

J Psychosom Res 2021 01 13;140:110295. Epub 2020 Nov 13.

School of Mental Health, Wenzhou Medical University, Wenzhou, China; The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou, China. Electronic address:

Objective: Postpartum depression (PPD) has received increasing attention due to its harmful impacts and high incidence. PPD is affected by physiological and psychological factors, but the conclusions are not uniform at present, so this study explored the risk factors of postpartum depressive symptoms (PPDS) in Chinese population.

Methods: A total of 397 women attending the obstetric department of the First Affiliated Hospital of Wenzhou Medical University participated in the questionnaire survey, mainly through a cross sectional study. At 6 weeks postpartum, the Edinburgh Postpartum Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI) were used to assess PPDS and sleep quality, respectively.

Results: The incidence of probable PPDS in our study population was 14.6% at 6 weeks postpartum. Women with blood group A had an almost 3-fold greater risk of PPDS than those with blood group B (OR [95% CI], 2.99 [1.43-6.28], p = 0.004). After adjusting for potential confounding variables, the blood group A phenotype was significantly more prevalent in women with PPDS compared to blood group B (OR [95% CI], 2.65 [1.23-5.70], p = 0.01).

Conclusions: Compared to women with blood groups B, AB or O, women with blood group A had high odds of PPDS. If this result can be demonstrated and replicated in other populations, blood group A may be a useful predictor of risk for PPDS in Chinese postpartum women.
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http://dx.doi.org/10.1016/j.jpsychores.2020.110295DOI Listing
January 2021

SDF2L1 Inhibits Cell Proliferation, Migration, and Invasion in Nasopharyngeal Carcinoma.

Biomed Res Int 2020 7;2020:1970936. Epub 2020 Aug 7.

Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

The purpose of this study was to explore the relationship between stromal cell-derived factor 2-like 1 (SDF2L1) and nasopharyngeal carcinoma (NPC). 12 NPC tissues and 12 chronic nasopharyngitis tissues were involved in our study. Quantitative real-time PCR (qRT-PCR) and Western Blot were utilized to detect the expression of SDF2L1. Besides, immunofluorescence analysis was utilized to determine the protein expression of 97 paraffin-embedded NPC tissues and 58 nasopharyngitis tissues. Biological functional experiment included Cell Counting Kit-8 (CCK-8) assay, cell clone formation assay, cell scratch migration assay, Transwell migration assay, and Transwell invasion assay. All data were analyzed by SPSS. Results showed that downexpression of SDF2L1 was prominently present in NPC tissues and cells. Furthermore, silencing the expression of SDF2L1 promoted NPC proliferation, migration, and invasion in vitro, while overexpression of SDF2L1 has the opposite effect. In conclusion, SDF2L1 may act as a cancer suppressor gene, play a crucial role in the occurrence and development of NPC, and be a new therapeutic target or prognostic indicator for NPC.
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http://dx.doi.org/10.1155/2020/1970936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595765PMC
May 2021

ROS production and mitochondrial dysfunction driven by PU.1-regulated NOX4-p22 activation in Aβ-induced retinal pigment epithelial cell injury.

Theranostics 2020 19;10(25):11637-11655. Epub 2020 Sep 19.

Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Amyloid β (Aβ) deposition, an essential pathological process in age-related macular degeneration (AMD), causes retinal pigment epithelium (RPE) degeneration driven mostly by oxidative stress. However, despite intense investigations, the extent to which overoxidation contributes to Aβ-mediated RPE damage and its potential mechanism has not been fully elucidated. We performed tandem mass-tagged (TMT) mass spectrometry (MS) and bioinformatic analysis of the RPE-choroid complex in an Aβ-induced mouse model of retinal degeneration to obtain a comprehensive proteomic profile. Key regulators in this model were confirmed by reactive oxygen species (ROS) detection, mitochondrial ROS assay, oxygen consumption rate (OCR) measurement, gene knockout experiment, chromatin immunoprecipitation (ChIP), and luciferase assay. A total of 4243 proteins were identified, 1069 of which were significantly affected by Aβ and found to be enriched in oxidation-related pathways by bioinformatic analysis. Moreover, NADPH oxidases were identified as hub proteins in Aβ-mediated oxidative stress, as evidenced by mitochondrial dysfunction and reactive oxygen species overproduction. By motif and binding site analyses, we found that the transcription factor PU.1/Spi1 acted as a master regulator of the activation of NADPH oxidases, especially the NOX4-p22 complex. Also, PU.1 silencing impeded RPE oxidative stress and mitochondrial dysfunction and rescued the retinal structure and function. Our study suggests that PU.1 is a novel therapeutic target for AMD, and the regulation of PU.1 expression represents a potentially novel approach against excessive oxidative stress in Aβ-driven RPE injury.
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http://dx.doi.org/10.7150/thno.48064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546003PMC
June 2021

Weaker Braking Force, A New Marker of Worse Gait Stability in Alzheimer Disease.

Front Aging Neurosci 2020 11;12:554168. Epub 2020 Sep 11.

Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Braking force is a gait marker associated with gait stability. This study aimed to determine the alteration of braking force and its correlation with gait stability in Alzheimer disease (AD). A total of 32 AD patients and 32 healthy controls (HCs) were enrolled in this study. Gait parameters (braking force, gait variability, and fall risk) in the walking tests of Free walk, Barrier, and Count backward were measured by JiBuEn gait analysis system. Gait variability was calculated by the coefficient of variation (COV) of stride time, stance time, and swing time. The braking force of AD was significantly weaker than HCs in three walking tests ( < 0.001, < 0.001, = 0.007). Gait variability of AD showed significant elevation than HCs in the walking of Count backward (COV: = 0.013; COV: = 0.006). Fall risk of AD was significantly higher than HCs in three walking tests ( = 0.001, = 0.001, = 0.001). Braking force was negatively associated with fall risks in three walking tests ( < 0.001, < 0.001, < 0.001). There were significant negative correlations between braking force and gait variability in the walking of Free walk (COV: = 0.018; COV: = 0.013) and Barrier (COV: = 0.002; COV: = 0.001), but not Count backward (COV: = 0.888; COV: = 0.555). Braking force was weaker in AD compared to HCs, reflecting the worse gait stability of AD. Our study suggests that weakening of braking force may be a new gait marker to indicate cognitive and motor impairment and predict fall risk in AD.
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http://dx.doi.org/10.3389/fnagi.2020.554168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516124PMC
September 2020

Constructing Conductive Channels between Platinum Nanoparticles and Graphitic Carbon Nitride by Gamma Irradiation for an Enhanced Oxygen Reduction Reaction.

ACS Appl Mater Interfaces 2020 Oct 29;12(41):46095-46106. Epub 2020 Sep 29.

State Key Laboratory of Separation Membranes and Membrane Processes, School of Textile Science and Engineering, Tiangong University, Tianjin 300387, China.

Electrocatalytic performance of low-cost graphitic carbon nitride (g-CN) is greatly limited by its conductivity. In this work, an innovative method, gamma irradiation technology, was used to efficiently synthesize g-CN/Pt nanoparticle (CN/Pt) nanocomposites, which can construct conductive channels between the nanostructure g-CN and supported platinum nanoparticles (PtNPs). Then, the as-prepared CN/Pt nanocomposites were applied in the oxygen reduction reaction (ORR) as an electrocatalyst, which shows a small Tafel slope and the fast four-electron transfer path in the ORR. The oxygen reduction performance over the CN/Pt nanocomposite is much superior to that of the commercial Pt/C and mostly reported in g-CN-based electrodes. Experimental results have confirmed the fast charge transfer between PtNPs and g-CN through a metal-support interaction, and using gamma irradiation technique to disperse PtNPs on g-CN proves to be an effective strategy to enhance the catalytic performance of g-CN in ORR. Therefore, gamma irradiation may possess great potential for preparing CN/Pt nanocomposites as a highly efficient ORR catalyst.
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http://dx.doi.org/10.1021/acsami.0c12838DOI Listing
October 2020

Vitamin K2 Can Rescue the Dexamethasone-Induced Downregulation of Osteoblast Autophagy and Mitophagy Thereby Restoring Osteoblast Function and .

Front Pharmacol 2020 11;11:1209. Epub 2020 Aug 11.

Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Chronic long-term glucocorticoids (GC) use is associated with glucocorticoid-induced osteoporosis (GIOP) by inhibiting the survival and impairing the functions of osteoblasts. Autophagy and mitophagy play key roles in osteoblast differentiation, mineralization and survival, and mounting evidence have implicated osteoblast autophagy and mitophagy as a novel mechanism in the pathogenesis of GIOP. Vitamin K2 (VK2) is an essential nutrient supplement that have been shown to exert protective effects against osteoporotic bone loss including GIOP. In this study, we showed that the glucocorticoid dexamethasone (Dex) deregulated osteoblast autophagy and mitophagy by downregulating the expression of autophagic and mitophagic markers LC3-II, PINK1, Parkin. This consequently led to inhibition of osteoblast differentiation and mineralization function . Interestingly, co-treatment with VK2 significantly attenuated the Dex-induced downregulation of LC3-II, PINK1, Parkin, thereby restoring autophagic and mitophagic processes and normal osteoblastic activity. In addition, using an established rat model of GIOP, we showed that VK2 administration can protect rats against the deleterious effects of Dex on bone by reinstating autophagic and mitophagic activities in bone tissues. Collectively, our results provide new insights into the role of osteoblast autophagy and mitophagy in GIOP. Additionally, the use of VK2 supplementation to augment osteoblast autophagy/mitophagy may significantly improve clinical outcomes of GIOP patients.
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http://dx.doi.org/10.3389/fphar.2020.01209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431688PMC
August 2020

Narrow H3K4me2 is required for chicken PGC formation.

J Cell Physiol 2021 Feb 4;236(2):1391-1400. Epub 2020 Aug 4.

Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

The development of primordial germ cells (PGCs) undergoes epigenetic modifications. The study of histone methylation in regulating PGCs is beneficial to understand the development and differentiation mechanism of germ stem cells. Notably, it provides a theoretical basis for directed induction and mass acquisition in vitro. However, little is known about the regulation of PGC formation by histone methylation. Here, we found the high enrichment of H3K4me2 in the blastoderm, genital ridges, and testis. Chromatin immunoprecipitation sequencing was performed and the results revealed that genomic H3K4me2 is dynamic in embryonic stem cells, PGCs, and spermatogonial stem cells. This trend was consistent with the H3K4me2 enrichment in the gene promoter region. Additionally, narrow region triggered PGC-related genes (Bmp4, Wnt5a, and Tcf7l2) and signaling pathways (Wnt and transforming growth factor-β). After knocking down histone methylase Mll2 in vitro and vivo, the level of H3K4me2 decreased, inhibiting Cvh and Blimp1 expression, then repressing the formation of PGCs. Taken together, our study revealed the whole genome map of H3K4me2 in the formation of PGCs, contributing to improve the epigenetic study in PGC formation and providing materials for bird gene editing and rescue of endangered birds.
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http://dx.doi.org/10.1002/jcp.29945DOI Listing
February 2021

The auxiliary diagnostic value of prostate-specific antigen and α-methylacyl-CoA racemase in prostate cancer.

Oncol Lett 2020 Aug 21;20(2):1418-1422. Epub 2020 May 21.

Department of Nursing, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, P.R. China.

Prostate cancer (PCa) is one of the most common types of malignant tumor, which places a major burden on the health of men, worldwide. A prerequisite to ensure good treatment outcomes for patients with PCa is an accurate diagnosis. The present study aimed to investigate the diagnostic value of prostate-specific antigen (PSA) and α-methylacyl-CoA racemase (P504S) in PCa, using the tumor-associated immunolabels. In total, clinical data was collected from 125 patients undergoing prostate biopsy or surgery between January 2015 and September 2019, and stratified into: PCa (45), benign prostatic hyperplasia (BPH) (60) and unconfirmed diagnosis (20). Immunohistochemistry analysis was performed to assess PSA and P504S expression levels in each group compared with that in the controls (the normal tissue in each group was the internal control). The results demonstrated that the expression level of P504S was significantly higher in the PCa group compared with that in the BPH group. Furthermore, no significant association was observed in the PCa group between PSA and P504S expression levels, and the Gleason grading groups. A total of 20 unconfirmed diagnoses was verified via PSA/P504S. Taken together, the results suggest that combination PSA and P504S have a positive effect in identifying prostate cancer. However, PSA and P504S still have limitations in their diagnosis and the final results need to be carefully and comprehensively analyzed, thus further studies are required to determine their diagnostic values.
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http://dx.doi.org/10.3892/ol.2020.11658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377033PMC
August 2020

The auxiliary diagnostic value of prostate-specific antigen and α-methylacyl-CoA racemase in prostate cancer.

Oncol Lett 2020 Aug 21;20(2):1418-1422. Epub 2020 May 21.

Department of Nursing, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, P.R. China.

Prostate cancer (PCa) is one of the most common types of malignant tumor, which places a major burden on the health of men, worldwide. A prerequisite to ensure good treatment outcomes for patients with PCa is an accurate diagnosis. The present study aimed to investigate the diagnostic value of prostate-specific antigen (PSA) and α-methylacyl-CoA racemase (P504S) in PCa, using the tumor-associated immunolabels. In total, clinical data was collected from 125 patients undergoing prostate biopsy or surgery between January 2015 and September 2019, and stratified into: PCa (45), benign prostatic hyperplasia (BPH) (60) and unconfirmed diagnosis (20). Immunohistochemistry analysis was performed to assess PSA and P504S expression levels in each group compared with that in the controls (the normal tissue in each group was the internal control). The results demonstrated that the expression level of P504S was significantly higher in the PCa group compared with that in the BPH group. Furthermore, no significant association was observed in the PCa group between PSA and P504S expression levels, and the Gleason grading groups. A total of 20 unconfirmed diagnoses was verified via PSA/P504S. Taken together, the results suggest that combination PSA and P504S have a positive effect in identifying prostate cancer. However, PSA and P504S still have limitations in their diagnosis and the final results need to be carefully and comprehensively analyzed, thus further studies are required to determine their diagnostic values.
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http://dx.doi.org/10.3892/ol.2020.11658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377033PMC
August 2020

Serum Amyloid A: A Potential Biomarker Assessing Disease Activity in Systemic Lupus Erythematosus.

Med Sci Monit 2020 Jun 25;26:e923290. Epub 2020 Jun 25.

Department of Laboratory Medicine, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China (mainland).

BACKGROUND This study aimed to investigate the association between levels of serum amyloid A (SAA) and the activity of systemic lupus erythematosus (SLE). MATERIAL AND METHODS The study included 135 patients with SLE, including 52 patients with active SLE and 83 patients with inactive SLE and 149 healthy controls. The degree of activity of SLE was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K). Serum SAA levels were measured using a Cobas 8000 c702 modular analyzer. RESULTS The levels of SAA were significantly increased in patients with active SLE compared with patients with inactive SLE (median IQR, 16.65 mg/L; range, 9.35-39.68 mg/L, and median IQR, 2.30 mg/L, range, 1.30-4.80 mg/L) (p<0.001). Levels of SAA were significantly correlated with the SLEDAI-2K scores, the erythrocyte sedimentation rate (ESR), and hypersensitive C-reactive protein (Hs-CRP) in patients with SLE (r=0.726, p<0.001; r=0.631, p<0.001; r=0.774, p<0.001, respectively). Multivariate logistic regression analysis showed that the SAA values were independently associated with active SLE when controlled for white blood cell (WBC) count, red blood cell distribution width (RDW), ESR, and Hs-CRP (OR=1.772; p=0.01; 95% CI, 1.101-2.851). Receiver operating characteristic (ROC) curve analysis for SAA was used to identify patients with active SLE with an area under the curve of 0.971, a sensitivity of 90.4%, and a specificity of 94.0%. CONCLUSIONS SAA levels were significantly correlated with disease activity in patients with SLE.
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http://dx.doi.org/10.12659/MSM.923290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333508PMC
June 2020

High-salt diet decreases mechanical thresholds in mice that is mediated by a CCR2-dependent mechanism.

J Neuroinflammation 2020 Jun 9;17(1):179. Epub 2020 Jun 9.

The Alan Edwards Centre for Research on Pain, McGill University, 740, Dr. Penfield Avenue, Montreal, QC, H3A 0G1, Canada.

Background: Though it is well-known that a high-salt diet (HSD) is associated with many chronic diseases, the effects of long-term high-salt intake on physiological functions and homeostasis remain elusive. In this study, we investigated whether and how an HSD affects mouse nociceptive thresholds, and myeloid cell trafficking and activation.

Methods: Healthy C57BL/6 male and female mice were fed an HSD (containing 4% NaCl in chow and 1% NaCl in water) from the time of weaning for 3 to 4 months. Circulating monocytes, nerve macrophages, spinal microglia, and associated inflammatory responses were scrutinized using flow cytometry, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR) approaches. Mouse pain sensitivity to mechanical stimuli was monitored with von Frey tests along the experimental duration.

Results: Mice on an HSD have reduced mechanical thresholds. They feel more pain than those on a normal diet (ND), e.g., regular laboratory chow (0.3% NaCl in chow). An HSD induced not only a remarkable expansion of circulating monocytes, CCR2Ly6C inflammatory monocytes in particular, but also an accumulation of CD11bF4/80 macrophages in the peripheral nerves and an activation of Iba-1 spinal microglia. Replacing an HSD with a ND was unable to reverse the HSD-induced mechanical hypersensitivity or rescue the altered immune responses. However, treating HSD-fed mice with a chemokine receptor CCR2 antagonist effectively normalized the pain thresholds and immune cell profile in the periphery and spinal cord. An HSD failed to alter pain thresholds and myeloid cell activation in CCR2-deficient mice. Spinal microglial activation is required for HSD-induced mechanical hypersensitivity in male, but not in female mice.

Conclusion: Overall, this study provides evidence that an HSD has a long-term impact on physiological function. CCR2-mediated cellular response, including myeloid cell trafficking and associated inflammation, plays pivotal roles in salt-dietary modulation of pain sensitivity.
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http://dx.doi.org/10.1186/s12974-020-01858-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282096PMC
June 2020
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