Publications by authors named "Wenli Li"

216 Publications

The Efficacy of Tocilizumab in the Treatment of Patients with Refractory Immune-Mediated Necrotizing Myopathies: An Open-Label Pilot Study.

Front Pharmacol 2021 16;12:635654. Epub 2021 Mar 16.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

To evaluate the efficacy of tocilizumab (TCZ) in adult patients with refractory immune-mediated necrotizing myopathies (IMNMs) and investigate possible predictive biomarkers of the response to treatment with TCZ. Patients with refractory IMNM were enrolled in this open-label pilot observational study and received intravenous TCZ treatment. The clinical response was assessed after 6 months of TCZ treatment according to the 2016 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) response criteria for adult dermatomyositis and polymyositis. Muscle biopsies were performed to investigate muscle fiber regeneration by immunohistochemical staining of CD56. Serum levels of interleukin (IL)-6 were measured using a multiplex bead-based flow fluorescent immunoassay. The levels of muscle IL-6 mRNA were detected by real-time polymerase chain reaction. A total of 11 patients with refractory IMNM were enrolled in the study, including 3 anti-3-hydroxy-3-methylglutaryl-CoA reductase- and 8 anti-signal recognition particle-positive patients. Seven (63.6%) of these patients achieved clinically significant responses according to the 2016 ACR-EULAR myositis response criteria. Responders had higher baseline serum IL-6 and muscle IL-6 mRNA levels and percentage of CD56-positive muscle fibers than non-responders. Baseline serum IL-6 levels and the percentage of CD56-positive muscle fibers were positively correlated with total improvement score after 6 months of TCZ treatment. Furthermore, muscle fiber necrosis and muscle fiber size variation decreased in repeated muscle biopsies in five responders. Patients with refractory IMNM may respond to TCZ. Baseline serum IL-6 and muscle IL-6 mRNA levels and the percentage of CD56-positive muscle fibers may predict the response to TCZ treatment in these patients.
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http://dx.doi.org/10.3389/fphar.2021.635654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010666PMC
March 2021

The Effects of Artificially Dosed Adult Rumen Contents on Abomasum Transcriptome and Associated Microbial Community Structure in Calves.

Genes (Basel) 2021 Mar 16;12(3). Epub 2021 Mar 16.

Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.

This study aimed to investigate the changes in abomasum transcriptome and the associated microbial community structure in young calves with artificially dosed, adult rumen contents. Eight young bull calves were randomly dosed with freshly extracted rumen contents from an adult cow (high efficiency (HE), = 4), or sterilized rumen content (Con, = 4). The dosing was administered within 3 days of birth, then at 2, 4, and 6 weeks following the initial dosing. Abomasum tissues were collected immediately after sacrifice at 8 weeks of age. Five genera (; < 0.05) showed significant difference in abundance between the treatments. A total of 975 differentially expressed genes were identified ( < 0.05, fold-change > 1.5, mean read-counts > 5). Pathway analysis indicated that up-regulated genes were involved in immune system process and defense response to virus, while the down-regulated genes involved in ion transport, ATP biosynthetic process, and mitochondrial electron transport. Positive correlation (r > 0.7, < 0.05) was observed between gene and , which was significantly higher in the HE group. had a reported role in the immune system process. In conclusion, the dosing of adult rumen contents to calves can alter not only the composition of active microorganisms in the abomasum but also the molecular mechanisms in the abomasum tissue, including reduced protease secretion and decreased hydrochloric acid secretion.
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http://dx.doi.org/10.3390/genes12030424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999174PMC
March 2021

Machine Learning for Building Immune Genetic Model in Hepatocellular Carcinoma Patients.

J Oncol 2021 17;2021:6676537. Epub 2021 Mar 17.

Reproductive Medicine Center, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan, Guangdong, China.

Background: Hepatocellular carcinoma (HCC) is the leading liver cancer with special immune microenvironment, which played vital roles in tumor relapse and poor drug responses. In this study, we aimed to explore the prognostic immune signatures in HCC and tried to construct an immune-risk model for patient evaluation.

Methods: RNA sequencing profiles of HCC patients were collected from the cancer genome Atlas (TCGA), international cancer genome consortium (ICGC), and gene expression omnibus (GEO) databases (GSE14520). Differentially expressed immune genes, derived from ImmPort database and MSigDB signaling pathway lists, between tumor and normal tissues were analyzed with Limma package in environment. Univariate Cox regression was performed to find survival-related immune genes in TCGA dataset, and in further random forest algorithm analysis, significantly changed immune genes were used to generate a multivariate Cox model to calculate the corresponding immune-risk score. The model was examined in the other two datasets with recipient operation curve (ROC) and survival analysis. Risk effects of immune-risk score and clinical characteristics of patients were individually evaluated, and significant factors were then used to generate a nomogram.

Results: There were 52 downregulated and 259 upregulated immune genes between tumor and relatively normal tissues, and the final immune-risk model (based on SPP1, BRD8, NDRG1, KITLG, HSPA4, TRAF3, ITGAV and MAP4K2) can better differentiate patients into high and low immune-risk subpopulations, in which high score patients showed worse outcomes after resection ( < 0.05). The differentially enriched pathways between the two groups were mainly about cell proliferation and cytokine production, and calculated immune-risk score was also highly correlated with immune infiltration levels. The nomogram, constructed with immune-risk score and tumor stages, showed high accuracy and clinical benefits in prediction of 1-, 3- and 5-year overall survival, which is useful in clinical practice.

Conclusion: The immune-risk model, based on expression of SPP1, BRD8, NDRG1, KITLG, HSPA4, TRAF3, ITGAV, and MAP4K2, can better differentiate patients into high and low immune-risk groups. Combined nomogram, using immune-risk score and tumor stages, could make accurate prediction of 1-, 3- and 5-year survival in HCC patients.
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http://dx.doi.org/10.1155/2021/6676537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994091PMC
March 2021

Deciphering a Cyclodipeptide Synthase Pathway Encoding Prenylated Indole Alkaloids in .

Appl Environ Microbiol 2021 Mar 19. Epub 2021 Mar 19.

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

Cyclodipeptide synthases (CDPSs) catalyse the formation of cyclodipeptides using aminoacylated-tRNAs as substrates and have great potentials in the production of diverse 2,5-diketopiperazines (2,5-DKPs). Genome mining of NRRL B-24963 revealed a two-gene locus encoding a CDPS SazA and a unique fused enzyme SazB harboring two domains: phytoene-synthase-like prenyltransferase (PT) and methyltransferase (MT). Heterologous expression of the gene(s) in J1074 led to the production of four prenylated indole alkaloids, among which streptoazines A-C (3-5) are new compounds. Expression of different gene combinations showed that the SazA catalyzes the formation of (L-Trp-L-Trp) (cWW, ), followed by consecutive prenylation and methylation by SazB. Biochemical assays demonstrated that SazB is a bifunctional enzyme, catalyzing sequential /-prenylation(s) by SazB-PT and /-methylation(s) by SazB-MT. Of note substrate selectivity of SazB-PT and SazB-MT was probed, revealing the stringent specificity of SazB-PT but relative flexibility of SazB-MT.Natural products with 2,5-DKP skeleton have long sparked the interest in drug discovery and development. Recent advances in microbial genome sequencing have revealed that the potentials of CDPS-dependent pathways encoding new 2,5-DKPs are underexplored. In this study, we report the genome mining of a new CDPS-containing two-gene operon and activation of this cryptic gene cluster through heterologous expression, leading to the discovery of four indole 2,5-DKP alkaloids. The cWW-synthesizing CDPS SazA and the unusual PT-MT fused enzyme SazB were characterized. Our results expand the repertoire of CDPSs and associated tailoring enzymes, setting the stage for accessing diverse prenylated alkaloids using synthetic biology strategies.
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http://dx.doi.org/10.1128/AEM.02525-20DOI Listing
March 2021

Pre-weaning Ruminal Administration of Differentially-Enriched, Rumen-Derived Inocula Shaped Rumen Bacterial Communities and Co-occurrence Networks of Post-weaned Dairy Calves.

Front Microbiol 2021 26;12:625488. Epub 2021 Feb 26.

USDA-Agricultural Research Service, Dairy Forage Research Center, Madison, WI, United States.

Adult rumen fluid inoculations have been considered to facilitate the establishment of rumen microbiota of pre-weaned dairy calves. However, the sustained effects of the inoculations remain to be explored. In our previous study, 20 pre-weaned dairy calves had been dosed with four types of adult rumen inoculums [autoclaved rumen fluid, bacterial-enriched rumen fluid (BE), protozoal-enriched (PE), and BE + PE] weekly at 3 to 6 weeks of age. To verify the sustained effect of adult rumen inoculation, the rumen bacterial communities, fermentation characteristics, and animal performance measurements were measured after sacrifice from 20 post-weaned dairy bull calves (9 weeks of age). Ruminal pH tended to be lower in BE treated calves ( = 10). All PE treated calves had rumen ciliates (>10 cells per ml of rumen fluid). PE treated calves had greater VFA concentrations ( = 0.052), lower molar proportions of isobutyrate ( = 0.073), and butyrate ( = 0.019) compared to those of control calves. No treatment differences were found in all animal performance measurements. Both PE and BE inocula increased bacterial species richness, Faith's phylogenetic diversity, and Shannon's index in rumen liquid fractions. However, the relative proportion of those bacterial taxa possibly transferred from the donor's rumen was minor. Microbial network analysis showed different co-occurrence and mutually exclusive interactions between treatments of microbial inoculations. Collectively, adult rumen inoculations in pre-weaned dairy calves slightly altered the rumen bacteriome of post-weaned calves without changing fermentation and animal performance.
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http://dx.doi.org/10.3389/fmicb.2021.625488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952535PMC
February 2021

Pregnancy-induced changes in the transcriptome of the bovine corpus luteum during and after embryonic interferon-tau secretion.

Biol Reprod 2021 Mar 4. Epub 2021 Mar 4.

Department of Animal and Dairy Sciences and Endocrinology and Reproductive Physiology Program, University of Wisconsin-Madison, Madison, WI 53706, USA.

Understanding luteal maintenance during early pregnancy is of substantial biological and practical importance. Characterizing effects of early pregnancy, however, has historically been confounded by use of controls with potential exposure to early PGF pulses or differences in CL age. To avoid this, the present study utilized bihourly blood sampling to ensure control CL (n = 6) were of a similar age to CL from pregnant animals (n = 5), yet without exposure to PGF pulses. Additionally, CL from second month of pregnancy (n = 4) were analyzed to track fate of altered genes after cessation of embryonic interferon tau (IFNT) secretion. The major alteration in gene expression in first month of pregnancy occurred in interferon-stimulated genes (ISGs), with immune/interferon signaling pathways enriched in three independent over-representation analyses. Most ISGs decreased during second month of pregnancy, though, surprisingly, some ISGs remained elevated in the second month even after cessation of IFNT secretion. Investigation of luteolytic genes found few altered transcripts, in contrast to previous reports, likely due to removal of controls exposed to PGF pulses. An exception to this trend was decreased expression of transcription factor NR4A1. Beyond luteolytic genes and ISGs, over representation analyses highlighted the prevalence of altered genes within the extracellular matrix and regulation of IGF availability, confirming results of other studies independent of luteolytic genes. These results support the idea that CL maintenance in early pregnancy is related to lack of PGF exposure, although potential roles for CL expression of diverse ISGs and other pathways activated during early pregnancy remain undefined.
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http://dx.doi.org/10.1093/biolre/ioab034DOI Listing
March 2021

Tregs in Autoimmune Uveitis.

Adv Exp Med Biol 2021 ;1278:205-227

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Uveitis is a chronic disease with relapsing and remitting ocular attack, which requires corticosteroids and systemic immunosuppression to prevent severe vision loss. Classically, uveitis is referred to an autoimmune disease, mediated by pro-inflammatory Th17 cells and immunosuppressive CD4+CD25+FoxP3+ T-regulatory cells (Tregs). More and more evidence indicates that Tregs are involved in development, resolution, and remission of uveitis. Clinically, many researchers have conducted quantitative and functional analyses of peripheral blood from patients with different subtypes of uveitis, in an attempt to find the changing rules of Tregs. Consistently, using the experimental autoimmune uveitis (EAU) model, researchers have explored the development and resolution mechanism of uveitis in many aspects. In addition, many drug and Tregs therapy investigations have yielded encouraging results. In this chapter, we introduced the current understanding of Tregs, summarized the clinical changes in the number and function of patients with uveitis and the immune mechanism of Tregs involved in EAU model, as well as discussed the progress and shortcomings of Tregs-related drug therapy and Tregs therapy. Although the exact mechanism of Tregs-mediated uveitis protection remains to be elucidated, the strategy of Tregs regulation may provide a specific and meaningful way for the prevention and treatment of uveitis.
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http://dx.doi.org/10.1007/978-981-15-6407-9_11DOI Listing
February 2021

A DFT study on the adsorption of DNA nucleobases on the CN nanotubes as a sequencer.

J Mol Model 2021 Jan 30;27(2):57. Epub 2021 Jan 30.

Department of Science, Faculty of Enghelab Islami, Tehran Branch, Technical and Vocational University (TVU), Tehran, Iran.

Deoxyribonucleic acid (DNA) sequencing is a crucial issue for the cure of different kinds of diseases. Here, we computationally explored the effect of DNA nucleobases on the electronic properties and electrical conductivity of a zigzag (10,0) CN nanotube (CNNT) at B3LYP-gCP-D3 level of theory. Our calculations revealed that the binding energy of nucleobases shows the order of guanine (G) > cytosine (C) > thymine (T) > adenine (A). Based on the energy decomposition analysis (EDA), the G, C, and T strongly interact with the CNNT, but the A nucleobase adsorbed mainly via electrostatic attraction and dispersion forces. We exposed that the nucleobase size and its carbonyl group determine its adsorption behavior. The DNA nucleobase adsorption meaningfully increased the electrical conductivity of CNNT. The CNNT sensing response toward G, C, T, or A was predicted to be 131, 66, 60, or 10. Therefore, the CNNT might be applied to selectively detect the G, C, T, and A. Our findings expose the usefulness of CNNT as a next-generation DNA sequencer, suggesting new leads for future progresses in sustainable designs, superior sensing architectures, and bioelectronics.
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http://dx.doi.org/10.1007/s00894-021-04672-wDOI Listing
January 2021

Bacillaenes: Decomposition Trigger Point and Biofilm Enhancement in .

ACS Omega 2021 Jan 8;6(2):1093-1098. Epub 2021 Jan 8.

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

Bacillaenes are a class of poly-unsaturated enamines produced by strains that are notoriously unstable toward light, oxygen, and normal temperature. Herein, in an in-depth study of this highly unstable chemotype, the stability and biological function of bacillaenes were investigated. The structure change of the bacillaene scaffold was tracked by time-course H NMR data analysis coupled with the differential analysis of 2D-NMR spectra method, which was demonstrated to be a "domino" effect triggered by 4',5'- ( and ) configuration rearranged to trans ( and ). These findings provide the possibility for stabilizing the bacillaene scaffold by chemical modification of its trigger points. In the biofilm assay, compounds and accelerated self-biofilm formation in B-9987 at low concentrations of 1.0 and 0.1 μg/mL. Interestingly, bacillaenes play dual roles as antibiotic and biofilm enhancers in a dose-dependent manner, both of which serve in the self-protection of .
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http://dx.doi.org/10.1021/acsomega.0c03389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818078PMC
January 2021

AP2/ERF and R2R3-MYB family transcription factors: potential associations between temperature stress and lipid metabolism in Auxenochlorella protothecoides.

Biotechnol Biofuels 2021 Jan 15;14(1):22. Epub 2021 Jan 15.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.

Background: Both APETALA2/Ethylene Responsive Factor (AP2/ERF) superfamily and R2R3-MYB family were from one of the largest diverse families of transcription factors (TFs) in plants, and played important roles in plant development and responses to various stresses. However, no systematic analysis of these TFs had been conducted in the green algae A. protothecoides heretofore. Temperature was a critical factor affecting growth and lipid metabolism of A. protothecoides. It also remained largely unknown whether these TFs would respond to temperature stress and be involved in controlling lipid metabolism process.

Results: Hereby, a total of six AP2 TFs, six ERF TFs and six R2R3-MYB TFs were identified and their expression profiles were also analyzed under low-temperature (LT) and high-temperature (HT) stresses. Meanwhile, differential adjustments of lipid pathways were triggered, with enhanced triacylglycerol accumulation. A co-expression network was built between these 18 TFs and 32 lipid-metabolism-related genes, suggesting intrinsic associations between TFs and the regulatory mechanism of lipid metabolism.

Conclusions: This study represented an important first step towards identifying functions and roles of AP2 superfamily and R2R3-MYB family in lipid adjustments and response to temperature stress. These findings would facilitate the biotechnological development in microalgae-based biofuel production and the better understanding of photosynthetic organisms' adaptive mechanism to temperature stress.
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http://dx.doi.org/10.1186/s13068-021-01881-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811268PMC
January 2021

ppGalNAc-T4-catalyzed O-Glycosylation of TGF-β type Ⅱ receptor regulates breast cancer cells metastasis potential.

J Biol Chem 2020 Dec 3:100119. Epub 2020 Dec 3.

School of Life Science & Pharmacy, Dalian University of Technology, Panjin, China. Electronic address:

GalNAc-type O-glycosylation, initially catalyzed by polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts), is one of the most abundant and complex post-translational modifications of proteins. Emerging evidence has proven that aberrant ppGalNAc-Ts are involved in malignant tumor transformation. However, the exact molecular functions of ppGalNAc-Ts are still unclear. Here, the role of one isoform, ppGalNAc-T4, in breast cancer cell lines was investigated. The expression of ppGalNAc-T4 was found to be negatively associated with migration of breast cancer cells. Loss-of function studies revealed that ppGalNAc-T4 attenuated the migration and invasion of breast cancer cells by inhibiting the epithelial-mesenchymal transition (EMT) process. Correspondingly, transforming growth factor beta (TGF-β) signaling, which is the upstream pathway of EMT, was impaired by ppGalNAc-T4 expression. ppGalNAc-T4 knock-out decreased O-GalNAc modification of TGF-β type Ⅰ and Ⅱ receptor (TβR Ⅰ and Ⅱ) and led to the elevation of TGF-β receptor dimerization and activity. Importantly, a peptide from TβR Ⅱ was identified as a naked peptide substrate of ppGalNAc-T4 with a higher affinity than ppGalNAc-T2. Further, Ser31, corresponding to the extracellular domain of TβR Ⅱ, was identified as the O-GalNAcylation site upon in vitro glycosylation by ppGalNAc-T4. The O-GalNAc-deficient S31A mutation enhanced TGF-β signaling activity and EMT in breast cancer cells. Together, these results identified a novel mechanism of ppGalNAc-T4-catalyzed TGF-β receptors O-GalNAcylation that suppresses breast cancer cell migration and invasion via the EMT process. Targeting ppGalNAc-T4 may be a potential therapeutic strategy for breast cancer treatment.
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http://dx.doi.org/10.1074/jbc.RA120.016345DOI Listing
December 2020

Investigating the complex interplay between genotype and high-fat-diet feeding in the lactating mammary gland using the and knockout models.

Am J Physiol Endocrinol Metab 2021 03 11;320(3):E438-E452. Epub 2021 Jan 11.

Department of Animal and Dairy Sciences, University of Wisconsin, Madison, Wisconsin.

Obesity is a prevailing problem across the globe. Women who are obese have difficulty initiating and sustaining lactation. However, the impact of genetics and diet on breastfeeding outcomes is understudied. Here we explore the effect of diet and genotype on lactation. We utilized the low-density lipoprotein receptor (KO) transgenic mouse model as an obesity and hypercholesterolemia model. Additionally, we used the tryptophan hydroxylase 1 (-KO) mouse, recently identified as a potential anti-obesogenic model, to investigate if addition of -KO could ameliorate negative effects of obesity in -KO mice. We created a novel transgenic mouse line by combining the and [double knockout (DKO)] mice to study the interaction between the two genotypes. Female mice were fed a low-fat diet (LFD; 10% fat) or high-fat diet (HFD; 60% fat) from 3 wk of age through early [lactation (L3)] or peak lactation [lactation (L11)]. After 4 wk of consuming either LFD or HFD, female mice were bred. On L2 and L10, dams were milked to investigate the effect of diet and genotype on milk composition. Dams were euthanized on L3 or L11. There was no impact of diet or genotype on milk protein or triglycerides (TGs) on L2; however, by L10, KO and DKO dams had increased TG levels in milk. RNA-sequencing of L11 mammary glands demonstrated -KO dams fed HFD displayed enrichment of genes involved in immune system pathways. Interestingly, the DKO may alter vesicle budding and biogenesis during lactation. We also quantified macrophages by immunostaining for F4/80+ cells at L3 and L11. Diet played a significant role on L3 ( = 0.013), but genotype played a role at L11 ( < 0.0001) on numbers of F4/80+ cells. Thus the impact of diet and genotype on lactation differs depending on stage of lactation, illustrating complexities of understanding the intersection of these parameters. We have created a novel mouse model that is focused on understanding the intersection of diet and genotype on mammary gland function during lactation.
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http://dx.doi.org/10.1152/ajpendo.00456.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988787PMC
March 2021

Expansion of circulating peripheral TIGIT+CD226+ CD4 T cells with enhanced effector functions in dermatomyositis.

Arthritis Res Ther 2021 01 7;23(1):15. Epub 2021 Jan 7.

Department of Rheumatology, China-Japan Friendship Hospital, Ying Hua East Road, Chao Yang District, Beijing, 100029, People's Republic of China.

Background: T cell Ig and ITIM domain (TIGIT)/CD226 pathway has a critical role in regulating T cell responses and has come to the forefront in cancer as a promising immunotherapeutic target. However, its role in autoimmune diseases is just beginning to be elucidated. Dermatomyositis (DM) is an autoimmune disease, in which T cell dysregulation plays a pivotal role, and importantly, it is a common immune-related adverse event in response to treatment of cancers with immune checkpoint inhibitors, but no studies have implicated the TIGIT/CD226 axis in DM.

Methods: We recruited 30 treatment-naïve DM patients and 26 healthy controls. Flow cytometry analysis was used to investigate the co-expression of TIGIT and CD226 on T cells in blood samples. Magnetic bead or FACS-based cell isolation, T cell proliferation assay, and intracellular cytokine staining were performed to analyze the functions of different TIGIT/CD226 phenotypes. Recombinant proteins CD155, CD112, and anti-CD226 antibodies were used to suppress the function of TIGIT/CD226-expressing CD4 T cells.

Results: Four distinct subsets of T cells based on TIGIT/CD226 co-expression, TIGIT+CD226-, TIGIT+CD226+, TIGIT-CD226+, and TIGIT-CD226-, were identified and characterized in DM patients. Our data showed that the function of CD4 T cell subset varied by the TIGIT/CD226 phenotype. An elevated TIGIT+CD226+ CD4 subset with enhanced effector function was observed in patients with DM, especially the patients complicated with interstitial lung disease. This subpopulation was closely related to DM activity and decreased significantly in DM remission after treatment. Furthermore, the effector function of TIGIT+CD226+ CD4 subset could be suppressed by blocking CD226.

Conclusion: Our data revealed that the TIGIT and CD226 expression profiles could be used to identify functionally distinct subsets of CD4 T cells and TIGIT+CD226+ CD4 T cells is a significant subset in DM with enhanced frequency and effector function. This abnormal subset could be suppressed by blocking CD226, providing insight into the therapeutic target of the TIGIT/CD226 axis.
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http://dx.doi.org/10.1186/s13075-020-02397-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791775PMC
January 2021

Corrigendum to 'Stat2-Drp1 mediated mitochondrial mass increase is necessary for pro-inflammatory differentiation of macrophages'[Redox Biology 37 (2020) 101761].

Redox Biol 2021 Feb 29;39:101786. Epub 2020 Dec 29.

Department of Toxicology, Shanxi Provincial Key Lab of Free Radical Biology and Medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, China. Electronic address:

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http://dx.doi.org/10.1016/j.redox.2020.101786DOI Listing
February 2021

Cubic Membranes Formation in Synchronized Human Hepatocellular Carcinoma Cells Reveals a Possible Role as a Structural Antioxidant Defense System in Cell Cycle Progression.

Front Cell Dev Biol 2020 14;8:617406. Epub 2020 Dec 14.

Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Department of Toxicology, School of Public Health, Air Force Medical University (Fourth Military Medical University), Xi'an, China.

Cubic membranes (CMs) represent unique biological membrane structures with highly curved three-dimensional periodic minimal surfaces, which have been observed in a wide range of cell types and organelles under various stress conditions (e. g., starvation, virus-infection, and oxidation). However, there are few reports on the biological roles of CMs, especially their roles in cell cycle. Hence, we established a stable cell population of human hepatocellular carcinoma cells (HepG2) of 100% S phase by thymidine treatment, and determined certain parameters in G2 phase released from S phase. Then we found a close relationship between CMs formation and cell cycle, and an increase in reactive oxygen species (ROS) and mitochondrial function. After the synchronization of HepG2 cells were induced, CMs were observed through transmission electron microscope in G2 phase but not in G1, S and M phase. Moreover, the increased ATP production, mitochondrial and intracellular ROS levels were also present in G2 phase, which demonstrated a positive correlation with CMs formation by Pearson correlation analysis. This study suggests that CMs may act as an antioxidant structure in response to mitochondria-derived ROS during G2 phase and thus participate in cell cycle progression.
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http://dx.doi.org/10.3389/fcell.2020.617406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769198PMC
December 2020

Prevalence and Correlation of Metabolic Syndrome: A Cross-Sectional Study of Nearly 10 Million Multi-Ethnic Chinese Adults.

Diabetes Metab Syndr Obes 2020 9;13:4869-4883. Epub 2020 Dec 9.

Health Management Institute, Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China.

Purpose: This study aimed to examine the prevalence and correlates of metabolic syndrome (MetS) in multi-ethnic populations of Northwest China based on Large-scale provincial health checking data.

Patients And Methods: A total of 9,745,640 Chinese aged ≥18 years in Xinjiang, the largest autonomous region of multi-ethnic in China, were enrolled from Feb. to Sep. 2019. MetS was defined by modified Adult Treatment Panel (ATP III) criteria.

Results: The overall prevalence of MetS was 20.85% [Sex: 20.06% female, 21.56% male; Age: 39.22% 60-years and above, 26.32% 40- to 59-years and 9.56% 18- to 39-years; Ethnicity: 28.19% Hui followed by Han (26.39%), Uyghur (18.56%), Other (18.61%), Kazak (17.98%), Mongolian (17.87%), Kyrgyz (14.44%)]. People living in cities and towns (23.03%) or North (24.78%) had higher prevalence of MetS than rural (19.94%) and South (17.66%). Although the prevalence of hypertension, smoking, drinking and lack of physical activity were higher in Kyrgyz, Mongolian and Kazak than those of other ethnic groups, the risk of MetS was lower.

Conclusion: The results indicated that a high prevalence of MetS in Hui and Han groups and people living in cities and towns. Living in North Xinjiang and elder population tend to have higher prevalence of MetS. The prevention and management of MetS in these populations should be prioritized.
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http://dx.doi.org/10.2147/DMSO.S278346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737555PMC
December 2020

A novel bacterial phylum that participates in carbon and osmolyte cycling in the Challenger Deep sediments.

Environ Microbiol 2020 Dec 16. Epub 2020 Dec 16.

Institute of Deep-Sea Science and Engineering, Chinese Academy of Sciences, Sanya, China.

Large amounts of detrital organic matter and osmolytes accumulate in the sediments of hadal trenches (>6000 m depth) due to the funnelling effect. It is still unknown whether there are novel active microbes that depend on specific carbon sources in extreme and isolated environments. In this study, we present a novel active bacterial phylum, Candidatus Tianyabacteria in the FCB superphylum, which was enriched in sediments collected from the Challenger Deep. Genome binning resulted in high-quality Ca. Tianyabacteria genomes representing two Ca. Tianyabacteria lineages (L1 and L2) in sediments 0-21 cm below the surface (cmbsf); L1 tends to be abundant in the upper layers (0-9 cmbsf), and L2 seems to be more prevalent in the deeper layers (12-21 cmbsf). Gene annotation and transcriptomics results indicate that the two lineages might import and catalyse amino acids and myo-inositol into central carbon metabolism for a heterotrophic lifestyle. Probably due to differences in environmental oxygen levels, the L2 genomes harbour gene clusters responsible for denitrification and fermentation, while the L1 genomes encode octahaem cytochrome c and multicopper oxidase using unknown substrates. The Ca. Tianyabacteria are thus novel heterotrophic organisms that participate in processes of carbon, nitrogen and organic osmolyte cycling in hadal sediments.
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http://dx.doi.org/10.1111/1462-2920.15363DOI Listing
December 2020

ppGalNAc-T4-catalyzed O-Glycosylation of TGF-β type Ⅱ receptor regulates breast cancer cells metastasis.

J Biol Chem 2020 Nov 24. Epub 2020 Nov 24.

School of Life Science and Medicine,, Dalian University of Technology, China.

GalNAc-type O-glycosylation, initially catalyzed by polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts), is one of the most abundant and complex post-translational modifications of proteins. Emerging evidence has proven that aberrant ppGalNAc-Ts are involved in malignant tumor transformation. However, the exact molecular functions of ppGalNAc-Ts are still unclear. Here, the role of one isoform, ppGalNAc-T4, in breast cancer cell lines was investigated. The expression of ppGalNAc-T4 was found to be negatively associated with migration of breast cancer cells. Loss-of function studies revealed that ppGalNAc-T4 attenuated the migration and invasion of breast cancer cells by inhibiting the epithelial-mesenchymal transition (EMT) process. Correspondingly, transforming growth factor beta (TGF-β) signaling, which is the upstream pathway of EMT, was impaired by ppGalNAc-T4 expression. ppGalNAc-T4 knock-out decreased O-GalNAc modification of TGF-β type Ⅰ and Ⅱ receptor (TβR Ⅰ and Ⅱ) and led to the elevation of TGF-β receptor dimerization and activity. Importantly, a peptide from TβR Ⅱ was first identified as the naked peptide substrate of ppGalNAc-T4 with a higher affinity than ppGalNAc-T2. Further, Ser31, corresponding to the extracellular domain of TβR Ⅱ, was identified as the O-GalNAcylation site upon in vitro glycosylation by ppGalNAc-T4. The O-GalNAc-deficient S31A mutation enhanced TGF-β signaling activity and EMT in breast cancer cells. Together, these results identified a novel mechanism of ppGalNAc-T4-catalyzed TGF-β receptors O-GalNAcylation that suppresses breast cancer cell migration and invasion via the EMT process. Targeting ppGalNAc-T4 may be a potential therapeutic strategy for breast cancer treatment.
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http://dx.doi.org/10.1074/jbc.RA120.016345DOI Listing
November 2020

Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin-associated proteins reveal an O-GlcNAc-regulated genotoxic stress response.

Nat Commun 2020 11 19;11(1):5898. Epub 2020 Nov 19.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

O-GlcNAc modification plays critical roles in regulating the stress response program and cellular homeostasis. However, systematic and multi-omics studies on the O-GlcNAc regulated mechanism have been limited. Here, comprehensive data are obtained by a chemical reporter-based method to survey O-GlcNAc function in human breast cancer cells stimulated with the genotoxic agent adriamycin. We identify 875 genotoxic stress-induced O-GlcNAc chromatin-associated proteins (OCPs), including 88 O-GlcNAc chromatin-associated transcription factors and cofactors (OCTFs), subsequently map their genomic loci, and construct a comprehensive transcriptional reprogramming network. Notably, genotoxicity-induced O-GlcNAc enhances the genome-wide interactions of OCPs with chromatin. The dynamic binding switch of hundreds of OCPs from enhancers to promoters is identified as a crucial feature in the specific transcriptional activation of genes involved in the adaptation of cancer cells to genotoxic stress. The OCTF nuclear factor erythroid 2-related factor-1 (NRF1) is found to be a key response regulator in O-GlcNAc-modulated cellular homeostasis. These results provide a valuable clue suggesting that OCPs act as stress sensors by regulating the expression of various genes to protect cancer cells from genotoxic stress.
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http://dx.doi.org/10.1038/s41467-020-19579-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678849PMC
November 2020

Application of liver acquisition with volume acceleration enhanced sequence in improving the accuracy of reassessing organ-invasive rectal mucinous adenocarcinoma after chemoradiation.

Eur J Radiol 2020 Dec 26;133:109368. Epub 2020 Oct 26.

Department of Radiology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, 510655, China. Electronic address:

Objectives: To explore the ability of liver acquisition with volume acceleration contrast-enhanced sequence (LAVA-ce) to improve the accuracy of reassessing adjacent organ involvement by rectal mucinous adenocarcinoma (MC) after neoadjuvant therapy (NAT).

Methods: This study retrospectively enrolled twenty-five patients with MC who underwent pre- and post-NAT MRI, were staged as T4b using pre-NAT T weighted imaging, received NAT and underwent radical resection. All MR images were divided into two schemes, T weighted plus diffusion weighted imaging (TD protocol) and plus LAVA-ce (TDL protocol). All patients were scored on a 0-4 scale to reassess organ-invasive mucus components. Postoperative pathology was used to identify the involvement of surrounding organs (ypT4b). The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the consistency of the results with pathology after adding fs-CE sequence.

Results: Among 25 MC patients (15 males and 10 females, aged 21-89 years), 21 were restaged as yT4b after NAT by using TD, with an accuracy of 44.0 % (11/25), which was lower than the accuracy of staging patients with non-mucinous rectal adenocarcinoma (94.1 %, 96/102). The accuracy of MC restaging was improved by using TDL (23/25). The AUC of TDL was 0.857 (95 % CI, 0.660∼0.964), which was higher than that of TD (AUC, 0.611 [95 % CI, 0.397∼0.798]) (P = 0.019).

Conclusion: The LAVA-ce sequence can improve the accuracy of reevaluation and should be included in the MRI protocol for MC patients.
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http://dx.doi.org/10.1016/j.ejrad.2020.109368DOI Listing
December 2020

Effects of manganese and Bacillus subtilis on the reproductive performance, egg quality, antioxidant capacity, and gut microbiota of breeding geese during laying period.

Poult Sci 2020 Nov 26;99(11):6196-6204. Epub 2020 Aug 26.

College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China. Electronic address:

This experiment was conducted to investigate the effects of manganese (Mn) and Bacillus subtilis (BS) on the production performance, egg quality, antioxidant capacity, and gut microbiota of breeding geese during laying period. A total of 120 forty-six-week-old breeding geese (Wulong) were randomly assigned to 1 of 6 treatment diets formulated to supply 10, 20, and 30 mg/kg Mn with 5 × 10 CFU/kg or 2.5 × 10 CFU/kg BS for a 10-wk trial. Results showed that dietary supplementation with 20 and 30 mg/kg Mn could decrease the daily feed intake (DFI) of geese. Moreover, 30 mg/kg Mn significantly increased the laying rate. Besides, although Mn addition had no obvious effect on egg quality, 5 × 10 CFU/kg BS was found to elevate the hatching egg hatching rate and eggshell thickness. For the serum hormones, 30 mg/kg Mn promoted estradiol secretion, while 5 × 10 CFU/kg BS increased the level of follicle-stimulating hormone. Furthermore, 20 and 30 mg/kg Mn and 5 × 10 CFU/kg BS significantly enhanced the total antioxidant capacity by increasing the activity of total superoxide dismutases or decreasing the content of malondialdehyde. Dietary supplementation with 5 × 10 CFU/kg BS also increased the intestinal villus height and upregulated the abundance of Fusobacteria, Fusobacteriaceae, Fusobacterium, and Faecalibacterium in cecal content. In addition, 20 and 30 mg/kg Mn elevated the levels of Bacteroidetes, Bacteroidaceae, Bacteroides, and Ruminococcaceae but decreased Streptococcaceae. Importantly, an interaction effect was observed between Mn and BS on the DFI, egg mass, average egg size, and the abundance of Bacteroides as well as Faecalibacterium. In conclusion, dietary inclusion of Mn and BS could improve the production performance, egg quality, antioxidant capacity, intestinal structure, as well as gut microbiota. Supplementation of 30 mg/kg Mn and 5.0 × 10 CFU/kg BS provided the optimal effect.
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http://dx.doi.org/10.1016/j.psj.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647850PMC
November 2020

Dietary combined supplementation of iron and Bacillus subtilis enhances reproductive performance, eggshell quality, nutrient digestibility, antioxidant capacity, and hematopoietic function in breeder geese.

Poult Sci 2020 Nov 8;99(11):6119-6127. Epub 2020 Aug 8.

College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, People's Republic of China. Electronic address:

A 3 × 2 factorial arrangement of treatments was conducted to investigate the effects of iron (Fe, 40, 60, and 80 mg/kg) and Bacillus subtilis (2.5 × 10 and 5.0 × 10 CFU/kg) supplementation on reproductive performance, egg quality, nutrient digestibility, hormone levels, antioxidant indices, and hematological parameters in breeder geese. A total of one hundredtwenty 46-week-old Wulong breeder geese were randomly assigned to 1 of 6 dietary treatments with 4 replicates per treatment and 5 geese per replicate for 10 wk following 1 wk of adaption. Dietary Fe supplementation increased egg weight (P = 0.036), fertility (P = 0.022), serum total antioxidant capacity (P = 0.022), red blood cell (P = 0.001), hematocrit (HCT, P < 0.001), hemoglobin (HGB, P = 0.005), and mean corpuscular volume (MCV, P < 0.001). Dietary B. subtilis supplementation increased egg production (P = 0.025), eggshell thickness (P = 0.020), apparent phosphorus digestibility (P < 0.001), serum follicle stimulating hormone (P = 0.043), total antioxidant capacity (P < 0.001), HCT (P < 0.001), HGB (P < 0.001), and MCV (P = 0.025), and reduced malondialdehyde level (P = 0.008). The birds fed diets supplemented with 60 mg/kg Fe and 5 × 10 CFU/kg B. subtilis showed the highest percentage of hatched eggs (P = 0.004) and mean corpuscular hemoglobin (P < 0.001) among the 6 groups. Supplementation of 40 and 60 mg/kg Fe significantly increased the apparent digestibility of calcium compared with that of 80 mg/kg Fe in the birds fed 5.0 × 10 CFU/kg B. subtilis (P = 0.004). Supplementation with 60 and 80 mg/kg Fe in the birds fed 5 × 10 CFU/kg B. subtilis significantly decreased serum urea nitrogen level compared with other 4 groups (P = 0.022). In conclusion, the combination of Fe and B. subtilis effectively improves reproductive performance, eggshell quality, nutrient digestibility, antioxidant status, and hematopoietic function of breeder geese. Dietary addition of 60 mg/kg Fe and 5.0 × 10 CFU/kg B. subtilis was an optimum supplementation dose.
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http://dx.doi.org/10.1016/j.psj.2020.06.077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647764PMC
November 2020

Anaplastic thyroid carcinoma combined with sclerosing mucoepidermoid carcinoma with eosinophilia: A case report.

Medicine (Baltimore) 2020 Oct;99(42):e22783

Department of Pathology, Binzhou People's Hospital of Shandong Province, Binzhou, China.

Rationale: Anaplastic thyroid carcinoma (ATC) is a rare highly aggressive thyroid malignancy. Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia is also a rare low grade malignant thyroid neoplasm. To date, comorbidity of these 2 tumors in the thyroid gland has not been reported in the English literature.

Patient Concerns: Here, we present a case of a 67-year-old women with a 6-month history of mass of left neck. She complained of a painless mass in the right neck.

Diagnoses: Based on histopathological examination of H&E stained sections, immunohistochemical staining assay and molecular tests, the patient was diagnosed with ATC combined with sclerosing mucoepidermoid carcinoma with eosinophilia.

Interventions: The patient underwent radical surgery for thyroid cancer.

Outcomes: No complications, local recurrence or metastases were observed during a 1 year and 3 months follow-up after surgery.

Lessons: To the best of our knowledge, this is the first case report on ATC combined with sclerosing mucoepidermoid carcinoma with eosinophilia in the English literature. This condition can be easily misdiagnosed during thyroid fine needle cytology. Clinicians should perform morphological examination, immunohistochemistry and molecular tests on resected specimen to make a definitive diagnosis.
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http://dx.doi.org/10.1097/MD.0000000000022783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572036PMC
October 2020

Stat2-Drp1 mediated mitochondrial mass increase is necessary for pro-inflammatory differentiation of macrophages.

Redox Biol 2020 10 14;37:101761. Epub 2020 Oct 14.

Department of Toxicology, Shanxi Provincial Key Lab of Free Radical Biology and Medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, 710032, PR China. Electronic address:

Macrophage recruitment and pro-inflammatory differentiation are hallmarks of various diseases, including infection and sepsis. Although studies suggest that mitochondria may regulate macrophage immune responses, it remains unclear whether mitochondrial mass affects macrophage pro-inflammatory differentiation. Here, we found that lipopolysaccharide (LPS)-activated macrophages possess higher mitochondrial mass than resting cells. Therefore, this study aimed to explore the functional role and molecular mechanisms of increased mitochondrial mass in pro-inflammatory differentiated macrophages. Results show that an increase in the mitochondrial mass of macrophages positively correlates with inflammatory cytokine generation in response to LPS. RNA-seq analysis revealed that LPS promotes signal transducers and activators of transcription 2 (Stat2) and dynamin-related protein 1 (Drp1) expression, which are enriched in positive mitochondrial fission regulation. Meanwhile, knockdown or pharmacological inhibition of Drp1 blunts LPS-induced mitochondrial mass increase and pro-inflammatory differentiation. Moreover, Stat2 boosts Drp1 phosphorylation at serine 616, required for Drp1-mediated mitochondrial fission. LPS also causes Stat2-and Drp1-dependent biogenesis, which contributes to the generation of additional mitochondria. However, these mitochondria are profoundly remodeled, displaying fragmented morphology, loose cristae, reduced Δψm, and metabolic programming. Furthermore, these remodeled mitochondria shift their function from ATP synthesis to reactive oxygen species (ROS) production, which drives NFκB-dependent inflammatory cytokine transcription. Interestingly, an increase in mitochondrial mass with constitutively active phosphomimetic mutant of Drp1 (Drp1) boosted pro-inflammatory response in macrophages without LPS stimulation. In vivo, we also demonstrated that Mdivi-1 administration inhibits LPS-induced macrophage pro-inflammatory differentiation. Importantly, we observed Stat2 phosphorylation and Drp1-dependent mitochondrial mass increase in macrophages isolated from LPS-challenged mice. In conclusion, we comprehensively demonstrate that a Stat2-Drp1 dependent mitochondrial mass increase is necessary for pro-inflammatory differentiation of macrophages. Therefore, targeting the Stat2-Drp1 axis may provide novel therapeutic approaches for treating infection and inflammatory diseases.
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http://dx.doi.org/10.1016/j.redox.2020.101761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575803PMC
October 2020

Reduced expression of ppGalNAc-T4 promotes proliferation of human breast cancer cells.

Cell Biol Int 2021 Feb 31;45(2):320-333. Epub 2020 Oct 31.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Breast cancer, one of the most frequently diagnosed and aggressive malignancies, is the major cause of cancer-related death greatly threatening women health. Polypeptide N-acetylgalactosaminyltransferase 4 (ppGalNAc-T4), responsible for the initial step of mucin-type O-glycosylation, has been reported to be implicated in diverse types of human tumors. However, the biological role of ppGalNAc-T4 in breast cancer is still undetermined. In this study, we investigate the effects and mechanism of ppGalNAc-T4 to breast cancer cell proliferation. From analysis of high throughput RNA sequencing datasets of Gene Expression Omnibus and ArrayExpress, a positive correlation between ppGalNAc-T4 and the recurrence-free survival was observed in multigroup of human breast cancer datasets. Moreover, transcriptomes analysis using RNA-sequencing in MCF7 cells revealed that cell cycle-related genes induced the effects of ppGalNAc-T4 on breast cancer cell proliferation. Additionally, investigations showed that ppGalNAc-T4 impaired cell proliferation in MCF-7 and MDA-MB-231 breast cells. Furthermore, our results suggested that the ppGalNAc-T4 knockout activated Notch signaling pathway and enhanced cell proliferation. Collectively, our data indicated that ppGalNAc-T4 affected the proliferation of human breast cancer cells, which appears to be a novel target for understanding the underlying molecular mechanism of breast cancer.
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http://dx.doi.org/10.1002/cbin.11488DOI Listing
February 2021

Disrupted Coupling Between NAA and Functional Connectivity in Ventromedial Prefrontal Cortex of Drug-Naïve First-Episode Psychosis.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1738-1741

Ventromedial prefrontal cortex (vmPFC) is an important brain region involved in many psychological functions. Previous neuroimaging studies have shown disrupted function and altered metabolic level within vmPFC of schizophrenia (SCZ) patients. However, the linkage between the functional connectivity and its underlying neurobiological mechanism in SCZ remains unclear. In this study, we aimed to investigate the altered relationship between the functional connectivity strength (FCS) and metabolic concentrations within vmPFC in drug-naïve first-episode psychosis (FEP) patients using a combined functional magnetic resonance imaging (fMRI) and single-voxel proton magnetic resonance spectroscopy (H- MRS) technique. There were 26 drug-naïve FEP patients and 27 matched healthy controls participated this study. We have found altered correlation between FCS and N-acetylaspartate (NAA) in drug-naïve FEP patients. In addition, the glutamate and glutamine compounds (Glx) and NAA concentrations were positively correlated with Positive and Negative Symptoms Scale (PANSS) total scores. Our findings revealed the disrupted functional-metabolic coupling within vmPFC in drug-naïve FEP patients and provided useful insights in understanding the etiology of SCZ.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176293DOI Listing
July 2020

A New MRI-Defined Biomarker for Rectal Mucinous Adenocarcinoma: Mucin Pool Patterns in Determining the Efficacy of Neoadjuvant Therapy.

Front Oncol 2020 20;10:1425. Epub 2020 Aug 20.

School of Medicine, South China University of Technology, Guangzhou, China.

This work aims to study the relationship between MRI-defined mucin pool (MP) patterns prior to treatment and the efficacy of neoadjuvant therapy (NAT) in locally advanced rectal mucinous adenocarcinoma (RMAC). This retrospective study included 278 RMAC patients evaluated between January 2012 and January 2019. After having been trained by using 118 cases with postoperative pathological images, radiologists distinguished MRI-defined MP status as mixed type (MTMP) and separate type (STMP) in a NAT cohort (160 patients) in addition to tumor characteristics, invasion of mesorectal facia, and nodal status. Reader reproducibility was determined using the κ coefficient. The main outcome was the accuracy of MP dichotomy in predicting whether patients had tumor responsiveness or not. Among 278 cases, MTMP and STMP accounted for 49.6 and 50.4% of MPs, respectively. A total of 72 patients received neoadjuvant chemoradiotherapy and 88 received chemotherapy. The tumor responsiveness rate in the chemoradiotherapy group was higher than that in the chemotherapy group (58.3 vs. 21.6%, < 0.001). In the chemotherapy group, the tumor responsiveness rate in patients with MTMPs was lower than that in patients with STMPs (4.9 vs. 25.5%, = 0.002). The baseline MRI-defined MTMP was associated with lower responsiveness rates after NAT in the chemotherapy group (odds ratio, 11.050, with 95% CI, 2.368-51.571, = 0.002). MP dichotomy can be reliably evaluated by using MRI. In the chemotherapy group, MTMP may be a dependent predictor to indicate a lower likelihood of tumor responsiveness after NAT.
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http://dx.doi.org/10.3389/fonc.2020.01425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468516PMC
August 2020

Upregulation of a marine fungal biosynthetic gene cluster by an endobacterial symbiont.

Commun Biol 2020 Sep 23;3(1):527. Epub 2020 Sep 23.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China.

Fungal-bacterial associations are present in nature, playing important roles in ecological, evolutionary and medicinal processes. Here we report a fungus-bacterial symbiont from marine sediment. The bacterium lives inside the fungal mycelium yet is robust enough to survive independent of its host; the independently grown bacterium can infect the fungal host in vitro and continue to grow progenitively. The bacterial symbiont modulates the fungal host to biosynthesize a polyketide antimicrobial, spiromarmycin. Spiromarmycin appears to endow upon the symbiont pair a protective/defensive means of warding off competitor organisms, be they prokaryotic or eukaryotic microorganisms. Genomic analyses revealed the spiromarmycin biosynthetic machinery to be encoded, not by the bacterium, but rather the fungal host. This unique fungal-bacterial symbiotic relationship and the molecule/s resulting from it dramatically expand our knowledge of marine microbial diversity and shed important insights into endosymbionts and fungal-bacterial relationships.
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http://dx.doi.org/10.1038/s42003-020-01239-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511336PMC
September 2020

Peripheral blood CD4+ cell counts but not CD3+ and CD8+ cell counts are reduced in SARS-CoV-2 infection.

J Affect Disord 2020 12 23;277:375-378. Epub 2020 Aug 23.

Department of Infectious Diseases, Guangdong Second Provincial General Hospital, 466 Middle Xingang Road, Guangzhou 510317, Guangdong, China. Electronic address:

Background: The world is facing the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). T cell-induced immune responses during acute SARS-CoV-2 infection have rarely been reported.

Methods: We use cell counting chips and PCR arrays to offer the first insights into the T cell involved in the course of acute SARS-CoV-2 infection. All consecutive patients with suspected SARS-CoV-2 infection treated at the designated hospital between January 2020 and February 2020 were recruited for the study, and cases were confirmed by real-time RT-PCR. Baseline characteristics for inpatients were prospectively collected and analyzed.

Results: 96 patients with suspected SARS-CoV-2 infection in our center were screened for inclusion in the study. The median age of the patients was 39.0 years, and 47 (49.0%) were female. Multivariate logistic regression analysis showed that only the CD4+ cell counts were significantly lower in the infection group and slightly higher in the control group. Receiver operating characteristic curve analysis showed good discrimination power between subjects with and subjects without infection.

Limitations: This is a single-center study of patients with a specific ethnic background and lacks a mechanism.

Conclusions: These findings imply the importance of CD4+ T cells (but not CD8+ and CD3+ T cells) in SARS-CoV-2 infection associated pneumonia and indicate that CD4+ T cells might be important for the control of SARS-CoV-2.
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http://dx.doi.org/10.1016/j.jad.2020.08.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443336PMC
December 2020