Publications by authors named "Xinyu Li"

439 Publications

[Biological functions and ubiquitin modification of TBK1 in innate immunity].

Sheng Wu Gong Cheng Xue Bao 2021 Apr;37(4):1189-1204

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

The innate immune system initiates innate immune responses by recognizing pathogen-related molecular patterns on the surface of pathogenic microorganisms through pattern recognition receptors. Through cascade signal transduction, it activates downstream transcription factors NF-κB and interferon regulatory factors (IRFs), and then leads to the production of inflammatory cytokines and type Ⅰ interferon, which resists the infection of pathogenic microorganism. TBK1 is a central adapter protein of innate immune signaling pathway and can activate both NF-κB and IRFs. It is a key protein kinase in the process of anti-infection. The finetuning regulation of TBK1 is essential to maintain immune homeostasis and resist pathogen invasion. This paper reviews the biological functions and ubiquitin modification of TBK1 in innate immunity, to provide theoretical basis for clinical treatment of pathogenic infections and autoimmune diseases.
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http://dx.doi.org/10.13345/j.cjb.200397DOI Listing
April 2021

Promoter Methylation in Gastrointestinal Cancer.

Front Oncol 2021 23;11:653222. Epub 2021 Apr 23.

Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

The adenomatous polyposis coli () gene, known as tumor suppressor gene, has the two promoters 1A and 1B. Researches on have usually focused on its loss-of-function variants causing familial adenomatous polyposis. Hypermethylation, however, which is one of the key epigenetic alterations of the CpG sequence, is also associated with carcinogenesis in various cancers. Accumulating studies have successively explored the role of hypermethylation in gastrointestinal (GI) tumors, such as in esophageal, colorectal, gastric, pancreatic, and hepatic cancer. In sporadic colorectal cancer, the hypermethylation of CpG island in is even considered as one of the primary causative factors. In this review, we systematically summarized the distribution of gene methylation in various GI tumors, and attempted to provide an improved general understanding of DNA methylation in GI tumors. In addition, we included a robust overview of demethylating agents available for both basic and clinical researches. Finally, we elaborated our findings and perspectives on the overall situation of gene methylation in GI tumors, aiming to explore the potential research directions and clinical values.
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http://dx.doi.org/10.3389/fonc.2021.653222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103321PMC
April 2021

Graphene oxide exhibited positive effects on the growth of L.

Physiol Mol Biol Plants 2021 Apr 7;27(4):815-824. Epub 2021 Apr 7.

Institute of Carbon Materials Science, Shanxi Datong University, Datong, 037009 Shanxi Province People's Republic of China.

There is increasing evidence for graphene associated plant growth promotion, however, the chronic effects of soil-applied graphene remain largely unexplored. The present study investigated the morphological, physiological and biochemical responses of graphene oxide (GO) on L. over the concentration range of 0-100 mg/L for four months. Our results demonstrated that GO, with the best efficiency at 50 mg/L, could enhance the photosynthetic capacity of leaves, increase the yield and morphological characters of root and leaf, improve the nutrient (protein and amino acid) contents of leaf, without reducing the content of the main bioactive compound aloin. Compared with leaves, the effect of GO on root growth was more obvious. Although the electrolyte leakage and MDA content were raised at high concentrations, GO treatment did not increase the root antioxidant enzymes activity or decrease the root vigor, which excluding typical stress response. Furthermore, injection experiments showed that the GO in vivo did not change the plant growth state obviously. Taken together, our study revealed the role of GO in promoting growth by stimulating root growth and photosynthesis, which would provide theory basis for GO application in agriculture and forestry.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-021-00979-3.
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http://dx.doi.org/10.1007/s12298-021-00979-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055783PMC
April 2021

The predictive value of tumor infiltrating leukocytes in Hepatocellular Carcinoma: A systematic review and meta-analysis.

Eur J Surg Oncol 2021 May 4. Epub 2021 May 4.

Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. Electronic address:

Background: For Hepatocellular carcinoma (HCC) surgery either through resection or transplantation often provides the only chance for cure. Since hepatocarcinogenesis and postsurgical prognosis is not only dependent on cirrhosis but also on immune activation and exhaustion, many studies have investigated tumor infiltrating leukocyte (TIL) subsets. This systematic review and meta-analysis aims at describing the cell groups and their predictive power regarding overall (OS), disease free (DFS) and recurrence free survival (RFS).

Material And Methods: A systematic search of the PubMed database was conducted (PROSPERO 172324). Data on CD3, CD8, Treg, B cells, macrophages, neutrophil and NK-cells were collected from Pubmed and related references up to December 2018. Overall (OS), disease-free (DFS) and recurrence free survival (RFS) in dependence of high vs. low infiltration rates were compared using a random effects meta-analysis.

Results: Altogether data from 3541 patients enrolled in 20 publications were included. Except for Tregs and Neutrophils, heterogeneity analysis was found to be moderate to high across the studies. High CD3, CD8, NK-cell infiltration predicted better survival (OS, DFS and RFS; p < 0.05). Higher Treg and Neutrophil infiltration predicted lower OS and DFS. For Macrophages and B cells no difference in survival could be found.

Discussion: As with other solid tumors immune infiltration has a great influence on survival after resection. However, a considerable publication bias cannot be ruled out in mostly retrospective analyses. Nevertheless, in light of novel immune modulatory treatments this opens a new avenue towards effective and well-tolerated adjuvant treatment.
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http://dx.doi.org/10.1016/j.ejso.2021.04.042DOI Listing
May 2021

Combined application of pharyngeal volume and minimal cross-sectional area may be helpful in screening persons suspected of obstructive sleep apnea (OSA).

Sleep Breath 2021 May 8. Epub 2021 May 8.

Department of Otolaryngology, The second hospital of Hebei Medical University, Shijiazhuang, 050000, China.

Background: Obstructive sleep apnea (OSA) is a common disease that seriously affects human health and daily life. However, the gold standard for its diagnosis, polysomnography (PSG), is expensive resulting in inadequate diagnosis of this disease in primary clinics. Therefore, a simple and rapid method for initial screening for OSA is needed. Acoustic pharyngometry (APh) is an FDA-approved noninvasive method that is gradually being applied to screening for OSA.

Materials And Methods: In this study, we applied analysis with receiver operating characteristic (ROC) curves to explore how APh may play a greater role in the screening of subjects with suspected OSA. Patients admitted into the departments of otolaryngology at our hospital from March 2017 to May 2019 were recruited into the study. All subjects underwent PSG monitor and were separated into two groups according to the apnea-hypopnea index (AHI) from the PSG results: OSA group (AHI ≥ 5) and control group (AHI < 5). APh measurements and other indicators of the subjects, including age, height, and weight; Epworth Sleepiness Scale (ESS) score; and the pharynx examination, including the degree of tonsil enlargement and tongue hypertrophy, were also be recorded.

Results: The t-test results showed that almost all indicators except age and height have significant differences between the OSA group and control group. Subjects with OSA had greater weight, BMI, ESS, higher degree of tonsil enlargement, and tongue hypertrophy, while they had smaller minimal cross-sectional area (mCSA) and pharyngeal volume than the subjects in control group. The correlation analysis revealed that pharyngeal volume and mCSA were two helpful indicators to screen for OSA. Furthermore, we established the ROC curve and calculated the combining predictors (combining predictors = pharyngeal volume + mCSA * (- 2.347)/(- 0.225)). The area under the ROC curve (AUC) of combining predictors was 0.917 (95% CI 0.842-0.991, P < 0.001), which was higher than combinations of other two independent indicators. The cutoff point of combining predictors was found to be 59.84 (AUC = 0.917, sensitivity = 0.80, 1-specificity = 0.06, P < 0.001).

Conclusions: These findings suggest that APh is a simple, rapid, and economical detection method which may be useful in screening for OSA, especially in communities and primary clinics where PSG cannot be performed.
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http://dx.doi.org/10.1007/s11325-021-02358-4DOI Listing
May 2021

Iron induces two distinct Ca signalling cascades in astrocytes.

Commun Biol 2021 May 5;4(1):525. Epub 2021 May 5.

Practical Teaching Centre, School of Forensic Medicine, China Medical University, Shenyang, PR China.

Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca]) in astrocytes. Administration of Fe or Fe in μM concentrations evoked [Ca] in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca] through two distinct molecular cascades. Uptake of Fe by DMT1 inhibits astroglial Na-K-ATPase, which leads to elevation in cytoplasmic Na concentration, thus reversing Na/Ca exchanger and thereby generating Ca influx. Uptake of Fe by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP), thus triggering InsP receptor-mediated Ca release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload.
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http://dx.doi.org/10.1038/s42003-021-02060-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100120PMC
May 2021

Interfacial Chemistry Enables Stable Cycling of All-Solid-State Li Metal Batteries at High Current Densities.

J Am Chem Soc 2021 May 27;143(17):6542-6550. Epub 2021 Apr 27.

Materials Science and Engineering Program and Texas Materials Institute, University of Texas at Austin, Austin, Texas 78712, United States.

The application of flexible, robust, and low-cost solid polymer electrolytes in next-generation all-solid-state lithium metal batteries has been hindered by the low room-temperature ionic conductivity of these electrolytes and the small critical current density of the batteries. Both issues stem from the low mobility of Li ions in the polymer and the fast lithium dendrite growth at the Li metal/electrolyte interface. Herein, Mg(ClO) is demonstrated to be an effective additive in the poly(ethylene oxide) (PEO)-based composite electrolyte to regulate Li ion transport and manipulate the Li metal/electrolyte interfacial performance. By combining experimental and computational studies, we show that Mg ions are immobile in a PEO host due to coordination with ether oxygen and anions of lithium salts, which enhances the mobility of Li ions; more importantly, an - formed Li-conducting LiMgCl/LiF interfacial layer homogenizes the Li flux during plating and increases the critical current density up to a record 2 mA cm. Each of these factors contributes to the assembly of competitive all-solid-state Li/Li, LiFePO/Li, and LiNiMnCoO/Li cells, demonstrating the importance of surface chemistry and interfacial engineering in the design of all-solid-state Li metal batteries for high-current-density applications.
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http://dx.doi.org/10.1021/jacs.1c00752DOI Listing
May 2021

Incidence of diabetic ketoacidosis and its trends in patients with type 1 diabetes mellitus identified using a U.S. claims database, 2007-2019.

J Diabetes Complications 2021 Apr 20:107932. Epub 2021 Apr 20.

Epidemiology & Benefit-Risk Evaluation, Sanofi, 55 Corporate Drive, Bridgewater, NJ 08807, USA.

Diabetic ketoacidosis (DKA) is a common complication of type 1 diabetes mellitus (T1DM). We found that the incidence of DKA was 55.5 per 1000 person-years in US commercially insured patients with T1DM; age-sex-standardized incidence decreased at an average annual rate of 6.1% in 2018-2019 after a steady increase since 2011.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.107932DOI Listing
April 2021

Three-dimensional-printed individualized porous implants: A new "implant-bone" interface fusion concept for large bone defect treatment.

Bioact Mater 2021 Nov 6;6(11):3659-3670. Epub 2021 Apr 6.

Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, People's Republic of China.

Bone defect repairs are based on bone graft fusion or replacement. Current large bone defect treatments are inadequate and lack of reliable technology. Therefore, we aimed to investigate a simple technique using three-dimensional (3D)-printed individualized porous implants without any bone grafts, osteoinductive agents, or surface biofunctionalization to treat large bone defects, and systematically study its long-term therapeutic effects and osseointegration characteristics. Twenty-six patients with large bone defects caused by tumor, infection, or trauma received treatment with individualized porous implants; among them, three typical cases underwent a detailed study. Additionally, a large segmental femur defect sheep model was used to study the osseointegration characteristics. Immediate and long-term biomechanical stability was achieved, and the animal study revealed that the bone grew into the pores with gradual remodeling, resulting in a long-term mechanically stable implant-bone complex. Advantages of 3D-printed microporous implants for the repair of bone defects included 1) that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility, and 2) that osseointegration between the host bone and implants was achieved without bone grafting. Our osseointegration method, in which the "implant-bone" interface fusion concept was used instead of "bone-bone" fusion, subverts the traditional idea of osseointegration.
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http://dx.doi.org/10.1016/j.bioactmat.2021.03.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056181PMC
November 2021

Retraction Note: A fast, high-affinity fluorescent serotonin biosensor engineered from a tick lipocalin.

Nat Methods 2021 May;18(5):575

Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.

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http://dx.doi.org/10.1038/s41592-021-01148-wDOI Listing
May 2021

Identification of Crocin as a New hIAPP Amyloid Inhibitor via a Simple Yet Highly Biospecific Screening System.

Chem Biodivers 2021 Apr 22. Epub 2021 Apr 22.

Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, P. R. China.

Amylin (hIAPP) amyloid formation plays an important role in the pathogenesis of type 2 diabetes (T2D), which makes it a promising therapeutic target for T2D. In this study, we established a screening tool for identifying chemicals affecting hIAPP amyloid formation based on a reported genetic tool, which constantly tracks protein aggregates in Saccharomyces cerevisiae. In order to obtain the hIAPP with better aggregation ability, the gene of hIAPP was tandemly ligated to create 1×, 2×, 4× or 6×-hIAPP expressing strains. By measuring the cell density and fluorescence intensity of green fluorescent protein (GFP) regulated by the aggregation status of hIAPP, it was found that four intramolecular ligated hIAPP (4×hIAPP) could form obvious amyloids with mild toxicity. The validity and reliability of the screening tool were verified by testing six reported hIAPP inhibitors, including curcumin, epigallocatechin gallate and so on. Combined with surface plasmon resonance (SPR) and the screening tool, which could be a screening system for hIAPP inhibitors, we found that crocin specifically binds to hIAPP and acts inhibit amyloid formation of hIAPP. The effect of crocin was further confirmed by Thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM) analysis. Thus, a screening system for hIAPP amyloid inhibitors and a new mechanism of crocin on anti-T2D were obtained as a result of this study.
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http://dx.doi.org/10.1002/cbdv.202100270DOI Listing
April 2021

Resetting Weight Vectors in MOEA/D for Multiobjective Optimization Problems With Discontinuous Pareto Front.

IEEE Trans Cybern 2021 Apr 20;PP. Epub 2021 Apr 20.

When a multiobjective evolutionary algorithm based on decomposition (MOEA/D) is applied to solve problems with discontinuous Pareto front (PF), a set of evenly distributed weight vectors may lead to many solutions assembling in boundaries of the discontinuous PF. To overcome this limitation, this article proposes a mechanism of resetting weight vectors (RWVs) for MOEA/D. When the RWV mechanism is triggered, a classic data clustering algorithm DBSCAN is used to categorize current solutions into several parts. A classic statistical method called principal component analysis (PCA) is used to determine the ideal number of solutions in each part of PF. Thereafter, PCA is used again for each part of PF separately and virtual targeted solutions are generated by linear interpolation methods. Then, the new weight vectors are reset according to the interrelationship between the optimal solutions and the weight vectors under the Tchebycheff decomposition framework. Finally, taking advantage of the current obtained solutions, the new solutions in the decision space are updated via a linear interpolation method. Numerical experiments show that the proposed MOEA/D-RWV can achieve good results for bi-objective and tri-objective optimization problems with discontinuous PF. In addition, the test on a recently proposed MaF benchmark suite demonstrates that MOEA/D-RWV also works for some problems with other complicated characteristics.
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http://dx.doi.org/10.1109/TCYB.2021.3062949DOI Listing
April 2021

PRMT1-mediated H4R3me2a recruits SMARCA4 to promote colorectal cancer progression by enhancing EGFR signaling.

Genome Med 2021 Apr 14;13(1):58. Epub 2021 Apr 14.

The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China.

Background: Aberrant changes in epigenetic mechanisms such as histone modifications play an important role in cancer progression. PRMT1 which triggers asymmetric dimethylation of histone H4 on arginine 3 (H4R3me2a) is upregulated in human colorectal cancer (CRC) and is essential for cell proliferation. However, how this dysregulated modification might contribute to malignant transitions of CRC remains poorly understood.

Methods: In this study, we integrated biochemical assays including protein interaction studies and chromatin immunoprecipitation (ChIP), cellular analysis including cell viability, proliferation, colony formation, and migration assays, clinical sample analysis, microarray experiments, and ChIP-Seq data to investigate the potential genomic recognition pattern of H4R3me2s in CRC cells and its effect on CRC progression.

Results: We show that PRMT1 and SMARCA4, an ATPase subunit of the SWI/SNF chromatin remodeling complex, act cooperatively to promote colorectal cancer (CRC) progression. We find that SMARCA4 is a novel effector molecule of PRMT1-mediated H4R3me2a. Mechanistically, we show that H4R3me2a directly recruited SMARCA4 to promote the proliferative, colony-formative, and migratory abilities of CRC cells by enhancing EGFR signaling. We found that EGFR and TNS4 were major direct downstream transcriptional targets of PRMT1 and SMARCA4 in colon cells, and acted in a PRMT1 methyltransferase activity-dependent manner to promote CRC cell proliferation. In vivo, knockdown or inhibition of PRMT1 profoundly attenuated the growth of CRC cells in the C57BL/6 J-Apc CRC mice model. Importantly, elevated expression of PRMT1 or SMARCA4 in CRC patients were positively correlated with expression of EGFR and TNS4, and CRC patients had shorter overall survival. These findings reveal a critical interplay between epigenetic and transcriptional control during CRC progression, suggesting that SMARCA4 is a novel key epigenetic modulator of CRC. Our findings thus highlight PRMT1/SMARCA4 inhibition as a potential therapeutic intervention strategy for CRC.

Conclusion: PRMT1-mediated H4R3me2a recruits SMARCA4, which promotes colorectal cancer progression by enhancing EGFR signaling.
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http://dx.doi.org/10.1186/s13073-021-00871-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048298PMC
April 2021

Therapeutic effect of low-molecular-weight heparin on adult sepsis: a meta-analysis.

Ann Palliat Med 2021 Mar;10(3):3115-3127

Department of Critical Medicine, the Second Affiliated Hospital of Xi'an Medical University, Xi'an, China.

Background: Low-molecular-weight heparin (LMWH) is a part of standard supportive therapy for sepsis, but clinical research on anticoagulant therapy is still controversial. The aim of the present study was to explore the efficacy and safety of LMWH in adult septic patients by meta-analysis.

Methods: Information on randomized controlled trials was retrieved from PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and China Wanfang Database from the establishment of each database to February 20, 2020. The therapeutic efficacy indexes of LMWH for adult septic patients were analyzed by Stata15.0 software.

Results: A total of 684 septic patients were included in 10 trials. The results showed that, compared with conventional treatment, LMWH significantly reduced prothrombin time [mean difference (MD) =-0.48, 95% confidence interval (CI): -0.83 to -0.13], Acute Physiology And Chronic Health Evaluation II score (MD=-4.42, 95% CI: -5.50 to -3.33), and 28-day mortality [relative risk (RR) =0.52, 95% CI: 0.38-0.70], and increased platelet count (MD =34.99, 95% CI: 23.37-46.60). LMWH significantly reduced levels of tumor necrosis factor-α, interleukin-6, and D-dimer, and the incidence of multiple organ dysfunction syndrome (MODS), with statistically significant differences. In addition, LMWH did not increase bleeding events (RR =1.29, 95% CI: 0.76-2.17).

Conclusions: On the basis of routine treatment, LMWH can improve coagulation function, reduce inflammatory reaction and the risk of bleeding, reduce the incidence of MODS and 28-day mortality rate, and improve the prognosis of adult patients with sepsis.
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http://dx.doi.org/10.21037/apm-21-169DOI Listing
March 2021

Hinokitiol inhibits RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced bone loss in vivo.

Int Immunopharmacol 2021 Apr 5;96:107619. Epub 2021 Apr 5.

Department of Orthopedics, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, China. Electronic address:

Osteoporosis is a metabolic bone-loss disease characterized by abnormally excessive osteoclast formation and bone resorption. Identification of natural medicines that can inhibit osteoclastogenesis, bone resorption, and receptor activator of nuclear factor-κB ligand (RANKL)-induced signaling is necessary for improved treatment of osteoporosis. In this study, hinokitiol, a tropolone-related compound extracted from the heart wood of several cupressaceous plants, was found to inhibit RANKL-induced osteoclast formation and bone resorption in vitro. Hinokitiol inhibited early activation of the ERK, p38, and JNK-MAPK pathways, thereby suppressing the activity and expression of downstream factors (c-Jun, c-Fos, and NFATC1). Consistent with the above in vitro findings, hinokitiol treatment protected against ovariectomy-induced bone loss in vivo. Collectively, our results imply that hinokitiol can potentially serve as an effective agent for treating osteoclast-induced osteoporosis.
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http://dx.doi.org/10.1016/j.intimp.2021.107619DOI Listing
April 2021

Coriander Genomics Database: a genomic, transcriptomic, and metabolic database for coriander.

Hortic Res 2020 Apr 1;7(1):55. Epub 2020 Apr 1.

Center for Genomics and Biocomputing/College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei, 063210, China.

Coriander (Coriandrum sativum L.), also known as cilantro, is a globally important vegetable and spice crop. Its genome and that of carrot are models for studying the evolution of the Apiaceae family. Here, we developed the Coriander Genomics Database (CGDB, http://cgdb.bio2db.com/) to collect, store, and integrate the genomic, transcriptomic, metabolic, functional annotation, and repeat sequence data of coriander and carrot to serve as a central online platform for Apiaceae and other related plants. Using these data sets in the CGDB, we intriguingly found that seven transcription factor (TF) families showed significantly greater numbers of members in the coriander genome than in the carrot genome. The highest ratio of the numbers of MADS TFs between coriander and carrot reached 3.15, followed by those for tubby protein (TUB) and heat shock factors. As a demonstration of CGDB applications, we identified 17 TUB family genes and conducted systematic comparative and evolutionary analyses. RNA-seq data deposited in the CGDB also suggest dose compensation effects of gene expression in coriander. CGDB allows bulk downloading, significance searches, genome browser analyses, and BLAST searches for comparisons between coriander and other plants regarding genomics, gene families, gene collinearity, gene expression, and the metabolome. A detailed user manual and contact information are also available to provide support to the scientific research community and address scientific questions. CGDB will be continuously updated, and new data will be integrated for comparative and functional genomic analysis in Apiaceae and other related plants.
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http://dx.doi.org/10.1038/s41438-020-0261-0DOI Listing
April 2020

Nutrition and Functions of Amino Acids in Aquatic Crustaceans.

Adv Exp Med Biol 2021 ;1285:169-198

Department of Animal Science, Texas A&M University, College Station, TX, USA.

Crustaceans (e.g., shrimp and crabs) are a good source of protein-rich foods for human consumption. They are the second largest aquaculture species worldwide. Understanding the digestion of dietary protein, as well as the absorption, metabolism and functions of amino acids (AAs) and small peptides is essential to produce cost-effective and sustainable aquafeeds. Hepatopancreas (the midgut gland) is the main site for the digestion of dietary protein as well as the absorption of small peptides and AAs into the hemolymph. Besides serving as the building blocks of protein, AAs (particularly aspartate, glutamate, glutamine and alanine) are the primary metabolic fuels for the gut and extra-hepatopancreas tissues (e.g., kidneys and skeletal muscle) of crustaceans. In addition, AAs are precursors for the syntheses of glucose, lipids, HS, and low-molecular-weight molecules (e.g., nitric oxide, glutathione, polyamines, histamine, and hormones) with enormous biological importance, such as physical barrier, immunological and antioxidant defenses. Therefore, both nutritionally essential and nonessential AAs are needed in diets to improve the growth, development, molt rate, survival, and reproduction of crustaceans. There are technical difficulties and challenges in the use of crystalline AAs for research and practical production due to the loss of free AAs during feed processing, the leaching of in-feed free AAs to the surrounding water environment, and asynchronous absorption with peptide-bounded AAs. At present, much knowledge about AA metabolism and functions in crustaceans is based on studies of mammals and fish species. Basic research in this area is necessary to lay a solid foundation for improving the balances and bioavailability of AAs in the diets for optimum growth, health and wellbeing of crustaceans, while preventing and treating their metabolic diseases. This review highlights recent advances in AA nutrition and metabolism in aquatic crustacean species at their different life stages. The new knowledge is expected to guide the development of the next generation of their improved diets.
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http://dx.doi.org/10.1007/978-3-030-54462-1_9DOI Listing
March 2021

Nutrition and Functions of Amino Acids in Fish.

Adv Exp Med Biol 2021 ;1285:133-168

Department of Animal Science, Texas A&M University, College Station, TX, USA.

Aquaculture is increasingly important for providing humans with high-quality animal protein to improve growth, development and health. Farm-raised fish and shellfish now exceed captured fisheries for foods. More than 70% of the production cost is dependent on the supply of compound feeds. A public debate or concern over aquaculture is its environmental sustainability as many fish species have high requirements for dietary protein and fishmeal. Protein or amino acids (AAs), which are the major component of tissue growth, are generally the most expensive nutrients in animal production and, therefore, are crucial for aquatic feed development. There is compelling evidence that an adequate supply of both traditionally classified nutritionally essential amino acids (EAAs) and non-essential amino acids (NEAAs) in diets improve the growth, development and production performance of aquatic animals (e.g., larval metamorphosis). The processes for the utilization of dietary AAs or protein utilization by animals include digestion, absorption and metabolism. The digestibility and bioavailability of AAs should be carefully evaluated because feed production processes and AA degradation in the gut affect the amounts of dietary AAs that enter the blood circulation. Absorbed AAs are utilized for the syntheses of protein, peptides, AAs, and other metabolites (including nucleotides); biological oxidation and ATP production; gluconeogenesis and lipogenesis; and the regulation of acid-base balance, anti-oxidative reactions, and immune responses. Fish producers usually focus on the content or digestibility of dietary crude protein without considering the supply of AAs in the diet. In experiments involving dietary supplementation with AAs, inappropriate AAs (e.g., glycine and glutamate) are often used as the isonitrogenous control. At present, limited knowledge is available about either the cell- and tissue-specific metabolism of AAs or the effects of feed processing methods on the digestion and utilization of AAs in different fish species. These issues should be addressed to develop environment-friendly aquafeeds and reduce feed costs to sustain the global aquaculture.
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http://dx.doi.org/10.1007/978-3-030-54462-1_8DOI Listing
March 2021

Risk factors for ecchymosis in patients receiving rivaroxaban for thromboprophylaxis after total knee arthroplasty: a retrospective cohort study.

J Clin Pharm Ther 2021 Mar 25. Epub 2021 Mar 25.

Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

What Is Known And Objective: Ecchymosis of the limb is commonly seen after total knee arthroplasty (TKA) when using anticoagulants for thromboprophylaxis, but it is unknown which factors may predispose patients to an increased risk. The aim of this study was to evaluate risk factors for ecchymosis in patients receiving rivaroxaban after TKA.

Methods: A retrospective, single-centre cohort analysis was conducted. The electronic medical records of patients admitted to the Department of Orthopedics during January 2018 to December 2019 and who received rivaroxaban 10 mg daily after TKA were reviewed for documentation of ecchymosis. Baseline demographics, laboratory values and surgical information were included for analysing their relationship with ecchymosis.

Results And Discussion: A total of 227 patients were included in the study. Among them, 54 patients (23.8%) developed ecchymosis, and 173 did not. The ecchymosis group had a higher proportion of patients with a body weight >60 kg [83.33% vs. 50.00%, p = 0.0004] and hypertension [61.11% vs 41.46%, p = 0.0304]. The ecchymosis group also had a higher BMI [26.04 ± 2.71 kg/m vs 24.52 ± 3.18 kg/m , p = 0.0066] mean arterial pressure (MAP) recorded from post-operation day 1 to day 3 [105.21 mmHg vs 91.52 mmHg, p = 0.0003]. However, serum albumin concentrations before surgery [3.85 g/dL vs. 4.20 g/dL, p = 0.0225] and on post-operation day 3 [3.50 g/dL vs. 3.91 g/dL, p = 0.0370] were lower in the ecchymosis group. Serum haemoglobin on post-operation day 3 was also lower [10.07 g/dL vs. 11.57 g/dL, p = 0.0459]. Five risk factors for ecchymosis were identified by binary logistic regression: mean MAP (from POD1 to POD3) (OR=2.901, 95% CI: 2.522-3.293, p < 0.001), BMI (OR=2.513, 95% CI: 1.929-3.011, p < 0.001), history of hypertension (OR=2.661, 95% CI: 1.272-4.535, p = 0.032), post-surgery serum albumin level (OR=0.848, 95% CI: 0.735-0.977, p = 0.023) and post-surgery serum haemoglobin level (OR=0.943; 95% CI: 0.898-0.990, p = 0.018).

What Is New And Conclusion: The present analyses identified that BMI, history of hypertension, mean MAP (POD1 to POD3), post-surgery serum albumin level and post-surgery serum haemoglobin level were independent risk factors for rivaroxaban-related ecchymosis in patients who underwent TKA. These factors should be considered and optimized before starting rivaroxaban therapy.
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http://dx.doi.org/10.1111/jcpt.13420DOI Listing
March 2021

ModularBoost: an efficient network inference algorithm based on module decomposition.

BMC Bioinformatics 2021 Mar 24;22(1):153. Epub 2021 Mar 24.

State Key Laboratory of Industrial Control Technology, Institute of Cyber-Systems and Control, Zhejiang University, Zheda Road, 310027, Hangzhou, China.

Background: Given expression data, gene regulatory network(GRN) inference approaches try to determine regulatory relations. However, current inference methods ignore the inherent topological characters of GRN to some extent, leading to structures that lack clear biological explanation. To increase the biophysical meanings of inferred networks, this study performed data-driven module detection before network inference. Gene modules were identified by decomposition-based methods.

Results: ICA-decomposition based module detection methods have been used to detect functional modules directly from transcriptomic data. Experiments about time-series expression, curated and scRNA-seq datasets suggested that the advantages of the proposed ModularBoost method over established methods, especially in the efficiency and accuracy. For scRNA-seq datasets, the ModularBoost method outperformed other candidate inference algorithms.

Conclusions: As a complicated task, GRN inference can be decomposed into several tasks of reduced complexity. Using identified gene modules as topological constraints, the initial inference problem can be accomplished by inferring intra-modular and inter-modular interactions respectively. Experimental outcomes suggest that the proposed ModularBoost method can improve the accuracy and efficiency of inference algorithms by introducing topological constraints.
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http://dx.doi.org/10.1186/s12859-021-04074-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992795PMC
March 2021

Development and validation of a clinically applicable deep learning strategy (HONORS) for pulmonary nodule classification at CT: A retrospective multicentre study.

Lung Cancer 2021 May 11;155:78-86. Epub 2021 Mar 11.

Department of Diagnostic Radiology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China; Department of Diagnostic Radiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address:

Purpose: To propose a practical strategy for the clinical application of deep learning algorithm, i.e., Hierarchical-Ordered Network-ORiented Strategy (HONORS), and a new approach to pulmonary nodule classification in various clinical scenarios, i.e., Filter-Guided Pyramid NETwork (FGP-NET).

Materials And Methods: We developed and validated FGP-NET on a collection of 2106 pulmonary nodules on computed tomography images which combined screened and clinically detected nodules, and performed external test (n = 341). The area under the curves (AUCs) of FGP-NET were assessed. A comparison study with a group of 126 skilled radiologists was conducted. On top of FGP-NET, we built up our HONORS which was composed of two solutions. In the Human Free Solution, we used the high sensitivity operating point for screened nodules, but the high specificity operating point for clinically detected nodules. In the Human-Machine Coupling Solution, we used the Youden point.

Results: FGP-NET achieved AUCs of 0.969 and 0.847 for internal and external test. The AUCs of the subsets of the external test set ranged from 0.890 to 0.942. The average sensitivity and specificity of the 126 radiologists were 72.2 ± 15.1 % and 71.7 ± 15.5 %, respectively, while a higher sensitivity (93.3 %) but a relatively inferior specificity (64.0 %) were achieved by FGP-NET. HONORS-guided FGP-NET identified benign nodules with high sensitivity (sensitivity,95.5 %; specificity, 72.5 %) in the screened nodules, and identified malignant nodules with high specificity (sensitivity, 31.0 %; specificity, 97.5 %) in the clinically detected nodules. These nodules could be reliably diagnosed without any intervention from radiologists, via the Human Free Solution. The remaining ambiguous nodules were diagnosed with high performance, which however required manual confirmation by radiologists, via the Human-Machine Coupling Solution.

Conclusions: FGP-NET performed comparably to skilled radiologists in terms of diagnosing pulmonary nodules. HONORS, due to its high performance, might reliably contribute a second opinion, aiding in optimizing the clinical workflow.
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http://dx.doi.org/10.1016/j.lungcan.2021.03.008DOI Listing
May 2021

Addressing the role of 11β-hydroxysteroid dehydrogenase type 1 in the development of polycystic ovary syndrome and the putative therapeutic effects of its selective inhibition in a preclinical model.

Metabolism 2021 Mar 12;119:154749. Epub 2021 Mar 12.

Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China. Electronic address:

Background: Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder among reproductive-age women, and the leading cause of anovulatory infertility. 11β-hydroxysteroid dehydrogenases-1 (11β-HSD1) catalysing the conversion of inactive cortisone to active cortisol plays a crucial role in various metabolic diseases. However, whether 11β-HSD1 is associated with the pathogenesis of PCOS and whether 11β-HSD1 can be a treating target of PCOS remain unknown.

Methods: This study was first designed to explore the role of 11β-HSD1 in PCOS development and the effect of selective 11β-HSD1 inhibitor administration on PCOS treatment. Follicular fluid and granulosa cells (GCs) were collected from 32 non-PCOS patients and 37 patients with PCOS to measure cortisol and 11β-HSDs levels. Female Sprague-Dawley rats (3-week-old) were injected with dehydroepiandrosterone (DHEA) to induce PCOS and their ovaries were collected to measure the abundance of corticosterone (CORT) and 11β-HSDs. To determine the role of 11β-HSD1 in PCOS development, we overexpressed 11β-HSD1 in the ovaries of female rats (5-week-old) or knocked down the expression of 11β-HSD1 in the ovaries from PCOS rats via lentivirus injection. After lentivirus infection, the body weights, ovarian weights, estrous cycles, reproductive hormones and morphology of the ovary were analysed in rats from different experimental groups. Then to figure out the translational potential of the selective 11β-HSD1 inhibitor in treating PCOS, PCOS rats were treated with BVT.2733, a selective 11β-HSD1 inhibitor and a cluster of PCOS-like traits were analysed, including insulin sensitivity, ovulatory function and fertility of rats from the Control, PCOS and PCOS+BVT groups. Rat ovarian explants and human GCs were used to explore the effect of CORT or cortisol on ovarian extracellular matrix remodelling.

Results: The elevated expression of 11β-HSD1 contributed to the increased cortisol and corticosterone (CORT) concentrations observed in the ovaries of PCOS patients and PCOS rats respectively. Our results showed that ovarian overexpression of 11β-HSD1 induced a cluster of PCOS phenotypes in rats including irregular estrous cycles, reproductive hormone dysfunction and polycystic ovaries. While knockdown of ovarian 11β-HSD1 of PCOS rats reversed these PCOS-like changes. Additionally, the selective 11β-HSD1 inhibitor BVT.2733 alleviated PCOS symptoms such as insulin resistance (IR), irregular estrous cycles, reproductive hormone dysfunction, polycystic ovaries, ovulatory dysfunction and subfertility. Moreover, we showed that cortisol target ovarian insulin signalling pathway and ovarian extracellular matrix (ECM) remodelling in vivo, in ovarian explants and in GCs.

Conclusion: Elevated 11β-HSD1 abundance in ovarian is involved in the pathogenesis of PCOS by impairing insulin signalling pathway and ECM remodelling. Selective inhibition of 11β-HSD1 ameliorates a cluster of PCOS phenotypes. Our study demonstrates the selective 11β-HSD1 inhibitor as a novel and promising strategy for the treatment of PCOS.
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http://dx.doi.org/10.1016/j.metabol.2021.154749DOI Listing
March 2021

Higher choroidal thickness and lower choriocapillaris blood flow signal density based on optical coherence tomography angiography in diabetics.

Sci Rep 2021 Mar 11;11(1):5799. Epub 2021 Mar 11.

Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie-fang Road, Wuhan, Hubei, China.

Diabetes mellitus (DM) is one of the fastest growing chronic diseases in the world and one of the main causes of vision loss. Whether or not diabetic choroidopathy (DC) is involved in the initiation and progression of diabetic ocular complications needs to be explored. We included 54 diabetic eyes from 36 diabetic patients, and 54 healthy eyes from 32 control subjects after propensity scores matching. All of the subjects were given pupil light and dark adaptation examination and optical coherence tomography angiography (OCTA). Scotopic pupil diameter (SPD), pupil contraction amplitude, and velocity of pupil contraction of the diabetic group were significantly lower than that of the healthy control group (P < 0.05).Choroidal thickness at temporal quadrant (at 750 μm) and superior quadrant (at 1500 μm and 2250 μm) increased in diabetic group compared to control group(P < 0.05).In the diabetic group, choriocapillaris blood flow signal density (CCBFSD) in the macular area (diameter = 2000 μm) were significantly decreased compared with the healthy control group (P < 0.05). Apparent changes in pupil and choroidal blood flow were observed in the diabetic patients.
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http://dx.doi.org/10.1038/s41598-021-85065-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952557PMC
March 2021

A Network Pharmacology Approach to Reveal the Underlying Mechanisms of on the Treatment of Hepatocellular Carcinoma.

Evid Based Complement Alternat Med 2021 22;2021:8947304. Epub 2021 Feb 22.

Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510080, China.

Objective: To investigate the potential active ingredients and underlying mechanisms of (AA) on the treatment of hepatocellular carcinoma (HCC) based on network pharmacology.

Methods: In the present study, we used a network pharmacological method to predict its underlying complex mechanism of treating HCC. First, we obtained relative compounds of AA based on the traditional Chinese medicine systems pharmacology (TCMSP) database and collected potential targets of these compounds by target fishing. Then, we built HCC-related targets target by the oncogenomic database of hepatocellular carcinoma (OncoDB.HCC) and biopharmacological network (PharmDB-K) database. Based on the matching results between AA potential targets and HCC targets, we built a protein-protein interaction (PPI) network to analyze the interactions among these targets and screen the hub targets by topology. Furthermore, the function annotation and signaling pathways of key targets were performed by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking.

Results: A total of 19 main active ingredients of AA were screened as target prediction; then, 25 HCC-related common targets were seeked out via multiple HCC databases. The areas of nodes and corresponding degree values of EGFR, ESR1, CCND1, MYC, EGF, and PTGS2 were larger and could be easily found in the PPI network. Furthermore, GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis to accomplish the anti-HCC activity. The molecular docking analysis showed that quercetin could stably bind to the active pocket of EGFR protein 4RJ5 via LibDock.

Conclusion: The anticancer effects of AA on HCC were predicted to be associated with regulating tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis via various pathways such as the EGFR signaling pathway, ESR1 signaling pathway, and CCND1 signaling pathway. It is suggested that AA might be developed as a broad-spectrum antitumor drug based on its characteristics of multicomponent, multipath, and multitarget.
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http://dx.doi.org/10.1155/2021/8947304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920725PMC
February 2021

Community Composition and Co-Occurrence Patterns of Diazotrophs along a Soil Profile in Paddy Fields of Three Soil Types in China.

Microb Ecol 2021 Mar 3. Epub 2021 Mar 3.

Key Laboratory of Pollution Ecology and Environmental Engineering, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, 110164, China.

Diazotrophs play a key role in biological nitrogen (N) fixation. However, we know little about the distribution of the diazotrophic community along the soil profile in paddy fields. Here, we used Illumina MiSeq sequencing, targeting the nitrogenase reductase (nifH) gene, to investigate changes with depth (0-100 cm) in the diazotrophic community in paddy soils of three regions (Changshu, Hailun, and Yingtan) in China. The results indicated that most diazotrophs belonged to the phylum Proteobacteria, accounting for 78.05% of the total number of sequences. The diazotrophic diversity was generally highest in the 10-20 cm layer, and then significantly decreased with soil depth. Principal coordinate analysis and PERMANOVA indicated that the diazotrophic community structure was significantly affected by region and soil depth. There were obvious differences in the composition of the diazotrophic community between the topsoil (0-40 cm) and the subsoil (40-100 cm). Anaeromyxobacter, Sideroxydans, Methylomonas, Nostoc, Methanocella, and Methanosaeta were enriched in the topsoil, while Geobacter, Azoarcus, Bradyrhizobium, and Dechloromonas were concentrated in the subsoil. Furthermore, co-occurrence network analysis showed that the diazotrophic network in the topsoil was more complex than that in the subsoil. Distance-based redundancy analysis indicated that soil total C and N content and pH were the main factors influencing the vertical variation in the diazotrophic community. These results highlighted that depth has a great impact on the diazotrophic diversity, community composition, and co-occurrence patterns in paddy soil.
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http://dx.doi.org/10.1007/s00248-021-01716-9DOI Listing
March 2021

Nicotinamide Mononucleotide Alleviates Hyperosmolarity-Induced IL-17a Secretion and Macrophage Activation in Corneal Epithelial Cells/Macrophage Co-Culture System.

J Inflamm Res 2021 22;14:479-493. Epub 2021 Feb 22.

Department of Ophthalmology, Changshu No. 2 People's Hospital, Changshu, People's Republic of China.

Background: Hyperosmosis stress (HS) was a key pathological factor in the development of dry eye disease (DED). Nicotinamide mononucleotide (NMN) demonstrated protective effects in the corneal damage, however, its role in the HS-induced DED remained unclear.

Methods: A NaCl based HS in-vitro model (500 mOsm) was generated and used in a co-culture system including corneal epithelial cells (CEC) and macrophage cell line RAW264.7. The effect of NMN on NAD+ metabolism and the expression of HS biomarker, tonicity-responsive element binding protein (TonEBP), was studied in the CEC. The cellular activity, including cell viability, apoptosis status and lactate dehydrogenase (LDH) release through trypan blue staining, flow cytometry and LDH assay, respectively. The mitochondrial membrane potential (MMP) assay would be conducted using the JC1 kit. The expression of IL-17a were detected using RT-PCR, ELISA and Western blot. After co-culture with the CEC in different group for 24 h, the phagocytosis ability and macrophage polarization were assessed in RAW264.7 cells co-cultured with CEC with or without HS or NMN treatment. Besides, the involvement of Notch pathway in the RAW264.7 would be analyzed. The potential involvement of Sirtuin 1 (SIRT1) and IL-17a in the crosstalk between CEC and macrophage was studied with SIRT1 inhibitor EX 527 and anti-IL-17a monoclonal antibody, respectively.

Results: NMN treatment increased NAD+ concentration and thus improved cell viability, reduced apoptotic rate and decreased the LDH release in HS-treated CEC. Besides, NMN alleviated HS-induced MMP, intracellular ROS and LDH release. Besides, it was confirmed NMN improve SIRT1 function and decreased the HS related IL-17a expression in CEC and then alleviated macrophage phagocytosis ability and M1 polarization based on a CEC-macrophage co-culture system. Moreover, NMN treatment of CEC in the CEC could moderate the subsequent macrophage activation through Notch pathway. SIRT1 activation and IL-17a inhibition was regarded as key progress in the function of NMN based on the application of EX 527 and anti-IL-17a antibody in the CEC-macrophage co-culture system.

Conclusion: The findings demonstrated that NMN could alleviated HS-induced DED status through regulating the CEC/macrophage interaction. Our data pointed to the role of SIRT1, IL-17a and Notch pathway in the function of NMN and then provided updated knowledge of potential NMN application in the management of DED.
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http://dx.doi.org/10.2147/JIR.S292764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917392PMC
February 2021

The networks of mA-SARS-CoV-2 related genes and immune infiltration patterns in idiopathic pulmonary fibrosis.

Aging (Albany NY) 2021 03 1;13(5):6273-6288. Epub 2021 Mar 1.

Transplantation Center, The 3rd Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a poor prognosis. The current coronavirus disease 2019 (COVID-19) shares some similarities with IPF. SARS-CoV-2 related genes have been reported to be broadly regulated by N-methyladenosine (mA) RNA modification. Here, we identified the association between mA methylation regulators, COVID-19 infection pathways, and immune responses in IPF. The characteristic gene expression networks and immune infiltration patterns of mA-SARS-CoV-2 related genes in different tissues of IPF were revealed. We subsequently evaluated the influence of these related gene expression patterns and immune infiltration patterns on the prognosis/lung function of IPF patients. The IPF cohort was obtained from the Gene Expression Omnibus dataset. Pearson correlation analysis was performed to identify the correlations among genes or cells. The CIBERSORT algorithm was used to assess the infiltration of 22 types of immune cells. The least absolute shrinkage and selection operator (LASSO) and proportional hazards model (Cox model) were used to develop the prognosis prediction model. Our research is pivotal for further understanding of the cellular and genetic links between IPF and SARS-CoV-2 infection in the context of the COVID-19 pandemic, which may contribute to providing new ideas for prognosis assessment and treatment of both diseases.
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http://dx.doi.org/10.18632/aging.202725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993677PMC
March 2021

A fast, high-affinity fluorescent serotonin biosensor engineered from a tick lipocalin.

Nat Methods 2021 03 25;18(3):258-261. Epub 2021 Feb 25.

Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.

Serotonin (5-HT) is an important signaling monoamine and neurotransmitter. We report structure-guided engineering of a green fluorescent, genetically encoded serotonin sensor (G-GESS) from a 5-HT-binding lipocalin in the soft tick Argas monolakensis. G-GESS shows fast response kinetics and high affinity, specificity, brightness and photostability. We used G-GESS to image 5-HT dynamics in cultured cells, brain slices and behaving mice.
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http://dx.doi.org/10.1038/s41592-021-01078-7DOI Listing
March 2021

Integrating omics and traditional analyses to profile the synergistic toxicity of graphene oxide and triphenyl phosphate.

Environ Pollut 2020 Aug 1;263(Pt A):114473. Epub 2020 Apr 1.

Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin, 300350, China.

The increasing production and applications of graphene oxide (GO, a novel carbon nanomaterial) have raised numerous environmental concerns regarding its ecological risks. Triphenyl phosphate (TPhP) disperses in water and poses an increasing hazard to the ecosystem and human health. It is critical to study the environmental responses and molecular mechanisms of GO and TPhP together to assess both chemicals; however, this information is lacking. The present work revealed that GO promoted the bioaccumulation of TPhP in zebrafish larvae by 5.0%-24.3%. The TPhP-induced growth inhibition of embryos (malformation, mortality, heartbeat, and spontaneous movement) at environmentally relevant concentrations was significantly amplified by GO, and these results were supported by the downregulated levels of genes and proteins associated with cytoskeletal construction and cartilage and eye development. TPhP induced negligible alterations in the genes or proteins involved in oxidative stress and apoptosis, but those related proteins were all upregulated by GO. GO and TPhP coexposure activated the mTOR signaling pathway and subsequently promoted apoptosis in zebrafish by potentiating the oxidative stress induced by TPhP, presenting synergistic toxicity. These findings highlight the potential risks and specific molecular mechanisms of combining emerging carbon nanomaterials with coexisting organic contaminants.
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http://dx.doi.org/10.1016/j.envpol.2020.114473DOI Listing
August 2020

Enhancing the potential of aged human articular chondrocytes for high-quality cartilage regeneration.

FASEB J 2021 Mar;35(3):e21410

Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Autologous chondrocyte implantation (ACI) is a regenerative procedure used to treat focal articular cartilage defects in knee joints. However, age has been considered as a limiting factor and ACI is not recommended for patients older than 40-50 years of age. One reason for this may be due to the reduced capacity of aged chondrocytes in generating new cartilage. Currently, the underlying mechanism contributing to aging-associated functional decline in chondrocytes is not clear and no proven approach exists to reverse chondrocyte aging. Given that chondrocytes in healthy hyaline cartilage typically display a spherical shape, believed to be essential for chondrocyte phenotype stability, we hypothesize that maintaining aged chondrocytes in a suspension culture that forces the cells to adopt a round morphology may help to "rejuvenate" them to a younger state, thus, leading to enhanced cartilage regeneration. Chondrocytes isolated from aged donors displayed reduced proliferation potential and impaired capacity in generating hyaline cartilage, compared to cells isolated from young donors, indicated by increased hypertrophy and cellular senescence. To test our hypothesis, the "old" chondrocytes were seeded as a suspension onto an agarose-based substratum, where they maintained a round morphology. After the 3-day suspension culture, aged chondrocytes displayed enhanced replicative capacity, compared to those grown adherent to tissue culture plastic. Moreover, chondrocytes subjected to suspension culture formed new cartilage in vitro with higher quality and quantity, with enhanced cartilage matrix deposition, concomitant with lower levels of hypertrophy and cellular senescence markers. Mechanistic analysis suggested the involvement of the RhoA and ERK1/2 signaling pathways in the "rejuvenation" process. In summary, our study presents a robust and straightforward method to enhance the function of aged human chondrocytes, which can be conveniently used to generate a large number of high-quality chondrocytes for ACI application in the elderly.
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http://dx.doi.org/10.1096/fj.202002386RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041516PMC
March 2021