Publications by authors named "Yunpeng Zhang"

184 Publications

Proteomic analysis of lung cancer cells reveals a critical role of BCAT1 in cancer cell metastasis.

Theranostics 2021 27;11(19):9705-9720. Epub 2021 Sep 27.

Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.

Metastasis is the major cause of high mortality in lung cancer. Exploring the underlying mechanisms of metastasis thus holds promise for identifying new therapeutic strategies that may enhance survival. We applied quantitative mass spectrometry to compare protein expression profiles between primary and metastatic lung cancer cells whilst investigating metastasis-related molecular features. We discovered that BCAT1, the key enzyme in branched-chain amino acid metabolism, is overexpressed at the protein level in metastatic lung cancer cells, as well as in metastatic tissues from lung cancer patients. Analysis of transcriptomic data available in the TCGA database revealed that increased BCAT1 transcription is associated with poor overall survival of lung cancer patients. In accord with a critical role in metastasis, shRNA-mediated knockdown of BCAT1 expression reduced migration of metastatic cells and the metastasis of these cells to distal organs in nude mice. Mechanistically, high levels of BCAT1 depleted α-ketoglutarate (α-KG) and promoted expression of SOX2, a transcription factor regulating cancer cell stemness and metastasis. Our findings suggest that BCAT1 plays an important role in promoting lung cancer cell metastasis, and may define a novel pathway to target as an anti-metastatic therapy.
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http://dx.doi.org/10.7150/thno.61731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490523PMC
September 2021

Bioinformatics analysis identifies CSF1R as an essential gene mediating Neuropathic pain - Experimental research.

Int J Surg 2021 Oct 7;95:106140. Epub 2021 Oct 7.

Department of Anesthesiology, Peking University People's Hospital, Beijing, China. Electronic address:

Background: Neuropathic pain (NP) severely affects the quality of life; however, there is no effective long-term treatment. The spinal dorsal horn (SDH) is an essential target for studying NP mechanisms and clinical treatments.

Materials And Methods: We searched the Gene Expression Omnibus (GEO) for the datasets of SDH microarray changes in mice NP models. Bioinformatics analysis was conducted to identify differentially expressed genes (DEGs), DEG enrichment pathways, and critical hub genes in the datasets. Finally, we explored the expression, function, and relevant mechanisms of the mouse NP model's most critical hub gene.

Results: Two SDH microarray datasets for the mice NP model were retrieved from GEO, GSE75072, and GSE111216. We found 43 overlapping DEGs in the datasets, primarily in the inflammatory and immune pathways. The most essential hub gene was the colony-stimulating factor 1 receptor (CSF1R). Seven days after creating the mouse NP model-spared nerve injury (SNI) model or Sham model, the expression of CSF1R and microglia increased significantly in the SDH of SNI group. PLX3397, an inhibitor of CSF1R, reduced the SDH CSF1R and microglia expression after SNI and significantly alleviated the hyperalgesia in the SNI mice.

Conclusion: SDH CSF1R participates in regulation NP, which is related to changes in the activity of microglia in the SDH.
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http://dx.doi.org/10.1016/j.ijsu.2021.106140DOI Listing
October 2021

Application of time-domain gating technique in water content measurement of gas-liquid two-phase flow.

Rev Sci Instrum 2021 Sep;92(9):094702

School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu 611731, China.

This paper introduces an application of the time-domain gating technique in water content measurement of gas-liquid two-phase flow. According to the principle that water and gas have different absorption effects on microwaves, a sensor with transmitting and receiving antennas is designed. Combined with the back propagation neural network, the water content of two-phase fluids can be obtained from the complex transmission coefficient (S) of antennas. In order to reduce the influence of the sensor structure on antenna measurement, the time-domain gating technique can be used to filter out the interference components in S so that the water content can be more easily predicted. Built on the above, an automatic test system is established. In the range of 0%-78%, the absolute test error of the water content is lower than 3%.
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http://dx.doi.org/10.1063/5.0055810DOI Listing
September 2021

Novel β-mannanase/GLP-1 fusion peptide high effectively ameliorates obesity in a mouse model by modifying balance of gut microbiota.

Int J Biol Macromol 2021 Sep 28;191:753-763. Epub 2021 Sep 28.

State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address:

We constructed a novel β-mannanase/GLP-1 fusion peptide, termed MGLP_1, and evaluated its ability to ameliorate obesity in a high-fat/high-sugar diet (HFSD)-induced mouse model. Eight-wk MGLP_1 treatment notably reduced obesity, as reflected by significant changes of body weight, serum triglyceride level, fatty liver and adipose tissue distribution. Amelioration of HFSD-induced gut dysbiosis by MGLP_1 was evidenced by reduced abundance ratio of bacterial phyla Firmicutes to Bacteroidetes, enhanced abundance of beneficial probiotic genera (Bifidobacterium, Lachnospiraceae, Ileibacterium), and reduced abundance of harmful genera (Clostridium, Romboutsia). Mechanisms of weight loss were investigated by comparing effects of treatment with MGLP_1 vs. prebiotics manno-oligosaccharides (MOS). MGLP_1 ameliorated gut microbiota imbalance by enhancing carbohydrate catabolism, whereas MOS promoted glycan synthesis and metabolism. Our findings, taken together, indicate that MGLP_1 fusion peptide has strong potential for amelioration of obesity by modifying relationships between gut microbiota and lipid and glucose metabolism.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.150DOI Listing
September 2021

Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function.

Cell Res 2021 Sep 24. Epub 2021 Sep 24.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.

The AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis. Although much has been learned on how low energy status and glucose starvation activate AMPK, how AMPK activity is properly controlled in vivo is still poorly understood. Here we report that UHRF1, an epigenetic regulator highly expressed in proliferating and cancer cells, interacts with AMPK and serves to suppress AMPK activity under both basal and stressed conditions. As a nuclear protein, UHRF1 promotes AMPK nuclear retention and strongly suppresses nuclear AMPK activity toward substrates H2B and EZH2. Importantly, we demonstrate that UHRF1 also robustly inhibits AMPK activity in the cytoplasm compartment, most likely as a consequence of AMPK nucleocytoplasmic shuttling. Mechanistically, we found that UHRF1 has no obvious effect on AMPK activation by upstream kinases LKB1 and CAMKK2 but inhibits AMPK activity by acting as a bridging factor targeting phosphatase PP2A to dephosphorylate AMPK. Hepatic overexpression of UHRF1 showed profound effects on glucose and lipid metabolism in wild-type mice but not in those with the liver-specific knockout of AMPKα1/α2, whereas knockdown of UHRF1 in adipose tissue led to AMPK activation and reduced sizes of adipocytes and lipogenic activity, highlighting the physiological significance of this regulation in glucose and lipid metabolism. Thus, our study identifies UHRF1 as a novel AMPK gate-keeper with critical roles in cellular metabolism.
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http://dx.doi.org/10.1038/s41422-021-00565-yDOI Listing
September 2021

Linking nuclear matrix-localized PIAS1 to chromatin SUMOylation via direct binding of histones H3 and H2A.Z.

J Biol Chem 2021 Sep 17;297(4):101200. Epub 2021 Sep 17.

Shanghai Key Laboratory of Regulatory Biology, Fengxian District Central Hospital-ECNU Joint Center of Translational Medicine, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Electronic address:

As a conserved posttranslational modification, SUMOylation has been shown to play important roles in chromatin-related biological processes including transcription. However, how the SUMOylation machinery associates with chromatin is not clear. Here, we present evidence that multiple SUMOylation machinery components, including SUMO E1 proteins SAE1 and SAE2 and the PIAS (protein inhibitor of activated STAT) family SUMO E3 ligases, are primarily associated with the nuclear matrix rather than with chromatin. We show using nuclease digestion that all PIAS family proteins maintain nuclear matrix association in the absence of chromatin. Of importance, we identify multiple histones including H3 and H2A.Z as directly interacting with PIAS1 and demonstrate that this interaction requires the PIAS1 SAP (SAF-A/B, Acinus, and PIAS) domain. We demonstrate that PIAS1 promotes SUMOylation of histones H3 and H2B in both a SAP domain- and an E3 ligase activity-dependent manner. Furthermore, we show that PIAS1 binds to heat shock-induced genes and represses their expression and that this function also requires the SAP domain. Altogether, our study reveals for the first time the nuclear matrix as the compartment most enriched in SUMO E1 and PIAS family E3 ligases. Our finding that PIAS1 interacts directly with histone proteins also suggests a molecular mechanism as to how nuclear matrix-associated PIAS1 is able to regulate transcription and other chromatin-related processes.
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http://dx.doi.org/10.1016/j.jbc.2021.101200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496182PMC
September 2021

Combined homologous recombination repair deficiency and immune activation analysis for predicting intensified responses of anthracycline, cyclophosphamide and taxane chemotherapy in triple-negative breast cancer.

BMC Med 2021 09 1;19(1):190. Epub 2021 Sep 1.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.

Background: Triple-negative breast cancer (TNBC) is a clinically aggressive disease with abundant variants that cause homologous recombination repair deficiency (HRD). Whether TNBC patients with HRD are sensitive to anthracycline, cyclophosphamide and taxane (ACT), and whether the combination of HRD and tumour immunity can improve the recognition of ACT responders are still unknown.

Methods: Data from 83 TNBC patients in The Cancer Genome Atlas (TCGA) was used as a discovery cohort to analyse the association between HRD and ACT chemotherapy benefits. The combined effects of HRD and immune activation on ACT chemotherapy were explored at both the genome and the transcriptome levels. Independent cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) were adopted to validate our findings.

Results: HRD was associated with a longer ACT chemotherapy failure-free interval (FFI) with a hazard ratio of 0.16 (P = 0.004) and improved patient prognosis (P = 0.0063). By analysing both HRD status and ACT response, we identified patients with a distinct TNBC subtype (ACT-S&HR-P) that showed higher tumour lymphocyte infiltration, IFN-γ activity and NK cell levels. Patients with ACT-S&HR-P had significantly elevated immune inhibitor levels and presented immune activation associated with the increased activities of both innate immune cells and adaptive immune cells, which suggested treatment with immune checkpoint blockade as an option for this subtype. Our analysis revealed that the combination of HRD and immune activation enhanced the efficiency of identifying responders to ACT chemotherapy (AUC = 0.91, P = 1.06e-04) and synergistically contributed to the clinical benefits of TNBC patients. A transcriptional HRD signature of ACT response-related prognostic factors was identified and independently validated to be significantly associated with improved survival in the GEO cohort (P = 0.0038) and the METABRIC dataset (P < 0.0001).

Conclusions: These findings highlight that HR deficiency prolongs FFI and predicts intensified responses in TNBC patients by combining HRD and immune activation, which provides a molecular basis for identifying ACT responders.
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http://dx.doi.org/10.1186/s12916-021-02068-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408988PMC
September 2021

Tissue signals imprint Aiolos expression in ILC2s to modulate type 2 immunity.

Mucosal Immunol 2021 Nov 4;14(6):1306-1322. Epub 2021 Aug 4.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Group 2 innate lymphoid cells (ILC2s) manifest tissue heterogeneity and are crucial modulators of regional immune responses. The molecular mechanisms regulating tissue ILC2 properties remain elusive. Here, we interrogate the signatures of ILC2s from five tissues at the transcriptome and epigenetic level. We have found that tissue microenvironment strongly shapes ILC2 identities. The intestine induces AiolosILC2s, whereas lung and pancreas enhance Galectin-1ILC2s. Though being a faithful gut ILC2 feature under the steady state, Aiolos is induced in non-intestinal ILC2s by pro-inflammatory cytokines. Specifically, IL-33 stimulates Aiolos expression in both human and mouse non-intestinal ILC2s. Functionally, Aiolos facilitates eosinophil recruitment by supporting IL-5 production and proliferation of ST2ILC2s through inhibiting PD-1. At the epigenetic level, ILC2 tissue characters are imprinted by open chromatin regions (OCRs) at non-promoters. Intestinal-specific transcription factor aryl hydrocarbon receptor (Ahr) binds to Ikzf3 (encoding Aiolos) locus, increases the accessibility of an intestinal ILC2-specific OCR, and promotes the Ikzf3 transcription by enhancing H3K27ac. Consequently, Ahr prevents ILC2s entering an "exhausted-like" state through sustaining Aiolos expression. Our work elucidates mechanism of ILC2 tissue adaptation and highlights Aiolos as a potential target of type 2 inflammation.
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http://dx.doi.org/10.1038/s41385-021-00431-5DOI Listing
November 2021

Dual-Mode Learning of Ambipolar Synaptic Phototransistor Based on 2D Perovskite/Organic Heterojunction for Flexible Color Recognizable Visual System.

Small 2021 09 28;17(36):e2102820. Epub 2021 Jul 28.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Artificial intelligence vision systems (AIVSs) with information sensing, processing, and storage functions are increasingly gaining attention in the science and technology community. Although synapse phototransistor (SPT) is one of the essential components in AIVSs, solution-processed large-area photonic synapses that can detect and recognize multi-wavelength light are highly desirable. One of the major challenges in this area is the inability of the available materials to distinguish colors from the visible light to the near-infrared (NIR) light for single carrier (hole-only or electron-only) SPTs owing to lack of cognitive elements. Herein, 2D perovskite/organic heterojunction (PEA SnI /Y6) ambipolar SPTs (POASPTs) are developed via solution process. The POASPTs can display dual-mode learning process, which can convert light signals into postsynaptic currents with excitement/inhibition modes (hole-transporting region) or inhibition/excitement (electron-transporting region). The POASPTs exhibit high responsivity to visible light (10 A W ) and NIR light (200 A W ), and effectively perform learning and memory simultaneously. The flexible POASPT arrays can successfully recognize the images of different colors of light. This study reveals that the fabricated POASPTs have great potentials in the development of large-area, high-efficiency, and low-cost AIVSs.
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http://dx.doi.org/10.1002/smll.202102820DOI Listing
September 2021

Comparative transcriptomic analysis of two Saccharopolyspora spinosa strains reveals the relationships between primary metabolism and spinosad production.

Sci Rep 2021 07 20;11(1):14779. Epub 2021 Jul 20.

Beijing Key Laboratory of Nutrition and Health and Food Safety, Nutrition and Health Research Institute, COFCO, Beijing, 102209, People's Republic of China.

Saccharopolyspora spinosa is a well-known actinomycete for producing the secondary metabolites, spinosad, which is a potent insecticides possessing both efficiency and safety. In the previous researches, great efforts, including physical mutagenesis, fermentation optimization, genetic manipulation and other methods, have been employed to increase the yield of spinosad to hundreds of folds from the low-yield strain. However, the metabolic network in S. spinosa still remained un-revealed. In this study, two S. spinosa strains with different spinosad production capability were fermented and sampled at three fermentation periods. Then the total RNA of these samples was isolated and sequenced to construct the transcriptome libraries. Through transcriptomic analysis, large numbers of differentially expressed genes were identified and classified according to their different functions. According to the results, spnI and spnP were suggested as the bottleneck during spinosad biosynthesis. Primary metabolic pathways such as carbon metabolic pathways exhibited close relationship with spinosad formation, as pyruvate and phosphoenolpyruvic acid were suggested to accumulate in spinosad high-yield strain during fermentation. The addition of soybean oil in the fermentation medium activated the lipid metabolism pathway, enhancing spinosad production. Glutamic acid and aspartic acid were suggested to be the most important amino acids and might participate in spinosad biosynthesis.
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http://dx.doi.org/10.1038/s41598-021-94251-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292330PMC
July 2021

Dissecting immune cell stat regulation network reveals biomarkers to predict ICB therapy responders in melanoma.

J Transl Med 2021 07 8;19(1):296. Epub 2021 Jul 8.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

Background: Immunotherapy is a revolutionary strategy in cancer therapy, but the resistance of which is one of the important challenges. Detecting the regulation of immune cells and biomarkers concerning immune checkpoint blockade (ICB) therapy is of great significance.

Methods: Here, we firstly constructed regulation networks for 11 immune cell clusters by integrating biological pathway data and single cell sequencing data in metastatic melanoma with or without ICB therapy. We then dissected these regulation networks and identified differently expressed genes between responders and non-responders. Finally, we trained and validated a logistic regression model based on ligands and receptors in the regulation network to predict ICB therapy response.

Results: We discovered the regulation of genes across eleven immune cell stats. Functional analysis indicated that these stat-specific networks consensually enriched in immune response corrected pathways and highlighted antigen processing and presentation as a core pathway in immune cell regulation. Furthermore, some famous ligands like SIRPA, ITGAM, CD247and receptors like CD14, IL2 and HLA-G were differently expressed between cells of responders and non-responders. A predictive model of gene sets containing ligands and receptors performed accuracy prediction with AUCs above 0.7 in a validation dataset suggesting that they may be server as biomarkers for predicting immunotherapy response.

Conclusions: In summary, our study presented the gene-gene regulation landscape across 11 immune cell clusters and analysis of these networks revealed several important aspects and immunotherapy response biomarkers, which may provide novel insights into immune related mechanisms and immunotherapy response prediction.
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http://dx.doi.org/10.1186/s12967-021-02962-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265039PMC
July 2021

Targeted Micellar Phthalocyanine for Lymph Node Metastasis Homing and Photothermal Therapy in an Orthotopic Colorectal Tumor Model.

Nanomicro Lett 2021 Jun 19;13(1):145. Epub 2021 Jun 19.

Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-021-00666-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214644PMC
June 2021

Downregulation of Prolactin-Induced Protein Promotes Osteogenic Differentiation of Periodontal Ligament Stem Cells.

Med Sci Monit 2021 Jun 7;27:e930610. Epub 2021 Jun 7.

School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China (mainland).

BACKGROUND Periodontal ligament stem cells (PDLSCs) are promising seed cells for bone tissue engineering and periodontal regeneration applications. However, the mechanism underlying the osteogenic differentiation process remains largely unknown. Previous reports showed that prolactin-induced protein (PIP) was upregulated after PDLSCs osteogenic induction. However, few studies have reported on the function of PIP in osteogenic differentiation. The purpose of the present study was to investigate the effect of PIP on osteogenic differentiation of PDLSCs. MATERIAL AND METHODS The expression pattern of PIP during PDLSCs osteogenic differentiation was detected and the effect of each component in the osteogenic induction medium on PIP was also tested by qRT-PCR. Then, the PIP knockdown cells were established using lentivirus. The knockdown efficiency was measured and the proliferation, apoptosis, and osteogenic differentiation ability were examined to determine the functional role of PIP on PDLSCs. RESULTS QRT-PCR showed that PIP was sustainedly upregulated during the osteogenic induction process and the phenomenon was mainly caused by the stimulation of dexamethasone in the induction medium. CCK-8 and flow cytometer showed that knocking down PIP had no influence on proliferation and apoptosis of PDLSCs. ALP staining and activity, Alizarin Red staining, and western blot analysis demonstrated PIP knockdown enhanced the osteogenic differentiation and mineralization of PDLSCs. CONCLUSIONS PIP was upregulated after osteogenic induction; however, PIP knockdown promoted PDLSCs osteogenic differentiation. PIP might be a by-product of osteogenic induction, and downregulating of PIP might be a new target in bone tissue engineering applications.
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http://dx.doi.org/10.12659/MSM.930610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194291PMC
June 2021

Analyses of key mRNAs and lncRNAs for different osteo-differentiation potentials of periodontal ligament stem cell and gingival mesenchymal stem cell.

J Cell Mol Med 2021 May 24. Epub 2021 May 24.

Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China.

Both human periodontal ligament stem cells (hPDLSCs) and human gingival mesenchymal stem cells (hGMSCs) are candidate seed cells for bone tissue engineering, but the osteo-differentiation ability of the latter is weaker than the former, and the mechanisms are unknown. To explore the potential regulation of mRNAs and long non-coding RNAs (lncRNAs), this study obtained the gene expression profiles of hPDLSCs and hGMSCs in both undifferentiated and osteo-differentiated conditions by microarray assay and then analysed the common and specific differentially expressed mRNAs and lncRNAs in hPDLSCs and hGMSCs through bioinformatics method. The results showed that 275 mRNAs and 126 lncRNAs displayed similar changing patterns in hPDLSCs and hGMSCs after osteogenic induction, which may regulate the osteo-differentiation in both types of cells. In addition, the expression of 223 mRNAs and 238 lncRNAs altered only in hPDLSCs after osteogenic induction, and 177 mRNAs and 170 lncRNAs changed only in hGMSCs. These cell-specific differentially expressed mRNAs and lncRNAs could underlie the different osteo-differentiation potentials of hPDLSCs and hGMSCs. Finally, dickkopf Wnt signalling pathway inhibitor 1 (DKK1) was proved to be one regulator for the weaker osteo-differentiation ability of hGMSCs through validation experiments. We hope these results help to reveal new mRNAs-lncRNAs-based molecular mechanism for osteo-differentiation of hPDLSCs and hGMSCs and provide clues on strategies for improving stem cell-mediated bone regeneration.
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http://dx.doi.org/10.1111/jcmm.16571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256345PMC
May 2021

Alternative splicing perturbation landscape identifies RNA binding proteins as potential therapeutic targets in cancer.

Mol Ther Nucleic Acids 2021 Jun 9;24:792-806. Epub 2021 Apr 9.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

Alternative splicing (AS) plays an important role in gene regulation, and AS perturbations are frequently observed in cancer. RNA binding protein (RBP) is one of the molecular determinants of AS, and perturbations in RBP-gene network activity are causally associated with cancer development. Here, we performed a systematic analysis to characterize the perturbations in AS events across 18 cancer types. We showed that AS alterations were prevalent in cancer and involved in cancer-related pathways. Given that the extent of AS perturbation was associated with disease severity, we proposed a computational pipeline to identify RBP regulators. Pan-cancer analysis identified a number of conserved RBP regulators, which play important roles in regulating AS of genes involved in cancer hallmark pathways. Our application analysis revealed that the expression of 68 RBP regulators helped in cancer subtyping. Specifically, we identified four subtypes of kidney cancer with differences in cancer hallmark pathway activities and prognosis. Finally, we identified the small molecules that can potentially target the RBP genes and suggested potential candidates for cancer therapy. In summary, our comprehensive AS perturbation landscape analysis identified RBPs as potential therapeutic targets in cancer and provided novel insights into the regulatory functions of RBPs in cancer.
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http://dx.doi.org/10.1016/j.omtn.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099609PMC
June 2021

Real-time indocyanine green lymphangiography in radical resection of right colon cancer allows the identification of chyle leakage.

Contemp Oncol (Pozn) 2021 23;25(1):64-67. Epub 2021 Feb 23.

Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Chyle leakage can be caused by abdominal surgery and managed successfully without surgical treatment; however, no preventive measures are available. Therefore, we introduce a new method to prevent post-operative chyle leakage. To investigate the role of indocyanine green (ICG) lymphangiography in the reduction of chyle fistula formation after radical resection of right colon cancer. Five patients with a diagnosis of right colon cancer undergoing laparoscopic radical colectomy with D3 lymph node dissection were examined in this study. At the end of the operation, two points of 2.5 mg ICG were injected subserosally at the proximal end of the anastomosis (1 ml per point). Then the surgical field was screened by using ICG fluorescence to accurately locate the chyle leakage. Chyle leakage was noted and repaired with a Hem-O-Lock. The volume of output of each drain after surgery was measured daily until the patients were discharged. We were able to observe ICG fluorescence in the lymphatic vessels within 3 minutes of ICG injection. This visualization allowed us to accurately locate and quickly repair chyle leakage within 5 minutes. Clinical observation after surgery and at a 1-month follow-up showed no chyle leakage in all 5 patients. Indocyanine green lymphangiography can feasibly guide the location and repair of chyle leakage after right colon cancer resection.
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http://dx.doi.org/10.5114/wo.2021.105076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063892PMC
February 2021

A procedure and device for determining complex material permittivity using the free-space resonance method.

Rev Sci Instrum 2021 Mar;92(3):035104

Chengdu Enchi Microwave Technology Co., Ltd., Chengdu, China.

The essential technologies of the complex permittivity of microwave dielectric materials are systematically designed, and the complex permittivity of materials is tested nondestructively by the free-space resonance method. A testing system was built by using a mobile surveying platform, and the complex dielectric constant of the material in the X band was nondestructively tested by using the algorithm of variable physical cavity length and constant physical cavity length. Focusing on the impact of variable physical cavity length on the test results, the cavity calibration technology is proposed to reduce the influence on the complex dielectric constant test of materials. The free-space resonance method was used to test the complex permittivity of polytetrafluoroethylene, glass steel plate (fiber reinforced plastics), and corundum plate. The results show that the test results of complex permittivity obtained by the two algorithms are consistent, and the error of complex permittivity is less than 5%.
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http://dx.doi.org/10.1063/5.0035361DOI Listing
March 2021

Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial.

Stroke Vasc Neurol 2021 Jun 1;6(2):160-169. Epub 2021 Apr 1.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Background: Studies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion.

Methods: We did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days.

Results: Of the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency.

Conclusions: Among patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.
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http://dx.doi.org/10.1136/svn-2021-000942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258050PMC
June 2021

Factors Controlling the Lower Radioactivity and Its Relation with Higher Organic Matter Content for Middle Jurassic Oil Shale in Yuqia Depression, Northern Qaidam Basin, China: Evidence from Organic and Inorganic Geochemistry.

ACS Omega 2021 Mar 8;6(11):7360-7373. Epub 2021 Mar 8.

Qinghai Geological Survey, Xining 810012, China.

Organic-rich oil shale with unusual lower radioactivity (expressed by GR) was found in Member 7 of Dameigou Formation, middle Jurassic (Jd) in Yuqia depression of northern Qaidam Basin, China. In order to systematically and contrastively investigate the factors controlling the lower GR and its relation with higher organic matter (OM) content (expressed by total organic carbon, abbr. TOC), organic and inorganic geochemical analyses were performed on samples consisting of oil shale and the underlying conformable contact dark shale from Well YQ-1Y. Our study shows that GR of Jd oil shale is mainly derived from uranium and thorium. Compared with dark shale, oil shale is characterized by higher OY and TOC, lower GR, and clay mineral content. During oil shale deposition, the paleoclimate was relatively arid, indicated by a decreased C value and siderite content as well as an increased carbonate content and . Under such paleoclimate conditions, sedimentary water became more anoxic, suggested by higher V/(V + Ni), pyrite content and lower pristane/phytane (Pr/Ph). From oil shale to dark shale deposition, according to analyses of AlO/TiO, TiO versus Zr, La/Sc versus Th/Co, La/Th versus Hf, and La-Th-Sc, the felsic igneous rock could always be deduced as the parent rock of provenance; however, the increasing arid paleoclimate resulted in weakened chemical weathering of provenance, inferred by relatively low chemical index of alteration, chemical index of weathering, and plagioclase index of alteration corresponding to the input degree of radioactive materials and other terrigenous detrital materials (TDMs), evidenced by Ti and Al contents and terrigenous (%). Meanwhile, the relatively high P/Ti and Ba/Al both indicated increased primary paleoproductivity. Together with the maximum flooding stage of oil shale deposition, the relatively low radioactivity tends to be associated with the inhibited input of clay minerals and radioactive materials, largely caused by increasing arid paleoclimate. The accompanying decreased TDM benefited primary paleoproductivity and anoxic conditions; their combined influence could induce sapropelic OM accumulation.
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http://dx.doi.org/10.1021/acsomega.0c05618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992071PMC
March 2021

HN1L/JPT2: A signaling protein that connects NAADP generation to Ca microdomain formation.

Sci Signal 2021 03 23;14(675). Epub 2021 Mar 23.

The Ca Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

NAADP-evoked Ca release through type 1 ryanodine receptors (RYR1) is a major mechanism underlying the earliest signals in T cell activation, which are the formation of Ca microdomains. In our characterization of the molecular machinery underlying NAADP action, we identified an NAADP-binding protein, called hematological and neurological expressed 1-like protein (HN1L) [also known as Jupiter microtubule-associated homolog 2 (JPT2)]. Gene deletion of in human Jurkat and primary rat T cells resulted in decreased numbers of initial Ca microdomains and delayed the onset and decreased the amplitude of global Ca signaling. Photoaffinity labeling demonstrated direct binding of NAADP to recombinant HN1L/JPT2. T cell receptor/CD3-dependent coprecipitation of HN1L/JPT2 with RYRs and colocalization of these proteins suggest that HN1L/JPT2 connects NAADP formation with the activation of RYR channels within the first seconds of T cell activation. Thus, HN1L/JPT2 enables NAADP to activate Ca release from the endoplasmic reticulum through RYR.
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http://dx.doi.org/10.1126/scisignal.abd5647DOI Listing
March 2021

Separation and extraction of non-thermal effects of strong microwave electric field on dielectric properties of materials based on time modulation and cavity perturbation method.

Rev Sci Instrum 2021 Feb;92(2):024712

School of Electronic Engineering, University of Electronic Science and Technology of China, Chengdu 611731, China.

The influence of strong microwave electric field (SMEF) on the dielectric properties of materials is the result of the joint action of microwave thermal effect and microwave non-thermal effect. Generally, the thermal effect of SMEF is stronger than the non-thermal effect, which makes the non-thermal effect of SMEF difficult to detect. Moreover, it is difficult to distinguish the influence of these two factors from each other. Therefore, the formation mechanism and characteristics of the non-thermal effect of SMEF have not been elucidated so far. In this paper, a separation and extraction model of the non-thermal effect of SMEF on the dielectric property of material is proposed based on the time modulation method and cavity perturbation method. By adjusting the interaction time between SMEF and materials, reducing the influence of microwave thermal effect, and strengthening the proportion of microwave non-thermal effect, the separation and extraction of the non-thermal effect of SMEF is realized. Through the designed re-entrant coaxial cavity, the corresponding test system is constructed and the typical materials are tested. Experimental results show that the proposed research method is feasible. The research method proposed in this paper provides an effective way for the follow-up study on the formation mechanism and characteristics of the non-thermal effect of SMEF on the dielectric properties of materials.
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http://dx.doi.org/10.1063/5.0037363DOI Listing
February 2021

Systematic analysis of enhancer regulatory circuit perturbation driven by copy number variations in malignant glioma.

Theranostics 2021 1;11(7):3060-3073. Epub 2021 Jan 1.

Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Hainan Medical University, Haikou 571199, China.

Enhancers are emerging regulatory regions controlling gene expression in diverse cancer types. However, the functions of enhancer regulatory circuit perturbations driven by copy number variations (CNVs) in malignant glioma are unclear. Therefore, we aimed to investigate the comprehensive enhancer regulatory perturbation and identify potential biomarkers in glioma. We performed a meta-analysis of the enhancer centered regulatory circuit perturbations in 683 gliomas by integrating CNVs, gene expression, and transcription factors (TFs) binding. We found widespread CNVs of enhancers during glioma progression, and CNVs were associated with the perturbations of enhancer activities. In particular, the degree of perturbations for amplified enhancers was much greater accompanied by the glioma malignant progression. In addition, CNVs and enhancers cooperatively regulated the expressions of cancer-related genes. Genome-wide TF binding profiles revealed that enhancers were pervasively regulated by TFs. A network-based analysis of TF-enhancer-gene regulatory circuits revealed a core TF-gene module (58 interactions including seven genes and 14 TFs) that was associated survival of patients with glioma (p < 0.001). Finally, we validated this prognosis-associated TF-gene regulatory module in an independent cohort. In summary, our analyses provided new molecular insights for enhancer-centered transcriptional perturbation in glioma therapy. Integrative analysis revealed enhancer regulatory perturbations in glioma and also identified a network module that was associated with patient survival, thereby providing novel insights into enhancer-centered cancer therapy.
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http://dx.doi.org/10.7150/thno.54150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847679PMC
July 2021

A numerical model applied to the simulation of cardiovascular hemodynamics and operating condition of continuous-flow left ventricular assist device.

Math Biosci Eng 2020 10;17(6):7519-7543

School of Electrical Engineering, Shandong University, Jinan 250061, China.

The mathematical modeling of the cardiovascular system is a simple and noninvasive method to comprehend hemodynamics and the operating mechanism of the mechanical circulatory assist device. In this study, a numerical model was developed to simulate hemodynamics under different conditions and to evaluate the operating condition of continuous-flow left ventricular assist device (LVAD). The numerical model consisted of a cardiovascular lumped parameter (CLP) model, a baroreflex model, and an LVAD model. The CLP model was established to simulate the human cardiovascular system including the left heart, right heart, systemic circulation, and pulmonary circulation. The baroreflex model was used to regulate left and right ventricular end-systolic elastances, systemic vascular resistance, and heart rate. The centrifugal pump HeartMate III used as an example to simulate the rotary pump dynamics at different operating speeds. Simulation results show that hemodynamics under normal, left ventricular failure and different levels of pump support conditions can be reproduced by the numerical model. Based on simulation results, HeartMate III operating speed can be maintained between 3600 rpm and 4400 rpm to avoid pump regurgitation and ventricular suction. Additionally, in the simulation system, the HeartMate III operating speed should be between 3600 rpm and 3800 rpm to provide optimal physiological perfusion. Thus, the developed numerical model is a feasible solution to simulate hemodynamics and evaluate the operating condition of continuous-flow LVAD.
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http://dx.doi.org/10.3934/mbe.2020384DOI Listing
October 2020

Improved photocatalyst: Elimination of triazine herbicides by novel phosphorus and boron co-doping graphite carbon nitride.

Sci Total Environ 2021 Feb 19;757:143810. Epub 2020 Nov 19.

Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China. Electronic address:

A non-metallic and low-cost novel phosphorus and boron co-doping graphite carbon nitride (PB-g-CN) photocatalyst was prepared by a facile thermal copolymerization of urea with BO and (NH)·HPO. The novel PB-g-CN exhibited excellent optical and electrical properties and the photocatalytic elimination efficiency for atrazine (AT, can make feminization of male frogs in the wild, and even induce reproductive cancers in humans.) has been greatly improved compared with the pristine g-CN. The results of characterization techniques indicate that the introduced B and P atoms most probably to substitute for sp-hybridized C atoms in triazine rings. O and h are the dominant active species to induce the elimination of AT demonstrated by the radical-trapping experiments. And a possible elimination pathway is proposed according to the detected main intermediates. In addition, PB-g-CN was applied to the simultaneous photocatalytic elimination of 9 triazine herbicides, and the effects of different initial concentrations, pH, fulvic acid (FA) and ion species on their elimination effects were studied. And it was proved that the photocatalytic performance of PB-g-CN did not significant decrease after 4 times of reuse.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143810DOI Listing
February 2021

LnCeCell: a comprehensive database of predicted lncRNA-associated ceRNA networks at single-cell resolution.

Nucleic Acids Res 2021 01;49(D1):D125-D133

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

Within the tumour microenvironment, cells exhibit different behaviours driven by fine-tuning of gene regulation. Identification of cellular-specific gene regulatory networks will deepen the understanding of disease pathology at single-cell resolution and contribute to the development of precision medicine. Here, we describe a database, LnCeCell (http://www.bio-bigdata.net/LnCeCell/ or http://bio-bigdata.hrbmu.edu.cn/LnCeCell/), which aims to document cellular-specific long non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) networks for personalised characterisation of diseases based on the 'One Cell, One World' theory. LnCeCell is curated with cellular-specific ceRNA regulations from >94 000 cells across 25 types of cancers and provides >9000 experimentally supported lncRNA biomarkers, associated with tumour metastasis, recurrence, prognosis, circulation, drug resistance, etc. For each cell, LnCeCell illustrates a global map of ceRNA sub-cellular locations, which have been manually curated from the literature and related data sources, and portrays a functional state atlas for a single cancer cell. LnCeCell also provides several flexible tools to infer ceRNA functions based on a specific cellular background. LnCeCell serves as an important resource for investigating the gene regulatory networks within a single cell and can help researchers understand the regulatory mechanisms underlying complex microbial ecosystems and individual phenotypes.
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http://dx.doi.org/10.1093/nar/gkaa1017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778920PMC
January 2021

Lnc2Cancer 3.0: an updated resource for experimentally supported lncRNA/circRNA cancer associations and web tools based on RNA-seq and scRNA-seq data.

Nucleic Acids Res 2021 01;49(D1):D1251-D1258

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

An updated Lnc2Cancer 3.0 (http://www.bio-bigdata.net/lnc2cancer or http://bio-bigdata.hrbmu.edu.cn/lnc2cancer) database, which includes comprehensive data on experimentally supported long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) associated with human cancers. In addition, web tools for analyzing lncRNA expression by high-throughput RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) are described. Lnc2Cancer 3.0 was updated with several new features, including (i) Increased cancer-associated lncRNA entries over the previous version. The current release includes 9254 lncRNA-cancer associations, with 2659 lncRNAs and 216 cancer subtypes. (ii) Newly adding 1049 experimentally supported circRNA-cancer associations, with 743 circRNAs and 70 cancer subtypes. (iii) Experimentally supported regulatory mechanisms of cancer-related lncRNAs and circRNAs, involving microRNAs, transcription factors (TF), genetic variants, methylation and enhancers were included. (iv) Appending experimentally supported biological functions of cancer-related lncRNAs and circRNAs including cell growth, apoptosis, autophagy, epithelial mesenchymal transformation (EMT), immunity and coding ability. (v) Experimentally supported clinical relevance of cancer-related lncRNAs and circRNAs in metastasis, recurrence, circulation, drug resistance, and prognosis was included. Additionally, two flexible online tools, including RNA-seq and scRNA-seq web tools, were developed to enable fast and customizable analysis and visualization of lncRNAs in cancers. Lnc2Cancer 3.0 is a valuable resource for elucidating the associations between lncRNA, circRNA and cancer.
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http://dx.doi.org/10.1093/nar/gkaa1006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779028PMC
January 2021

LincSNP 3.0: an updated database for linking functional variants to human long non-coding RNAs, circular RNAs and their regulatory elements.

Nucleic Acids Res 2021 01;49(D1):D1244-D1250

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

We describe an updated comprehensive database, LincSNP 3.0 (http://bioinfo.hrbmu.edu.cn/LincSNP), which aims to document and annotate disease or phenotype-associated variants in human long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) or their regulatory elements. LincSNP 3.0 has updated with several novel features, including (i) more types of variants including single nucleotide polymorphisms (SNPs), linkage disequilibrium SNPs (LD SNPs), somatic mutations and RNA editing sites have been expanded; (ii) more regulatory elements including transcription factor binding sites (TFBSs), enhancers, DNase I hypersensitive sites (DHSs), topologically associated domains (TADs), footprintss, methylations and open chromatin regions have been added; (iii) the associations among circRNAs, regulatory elements and variants have been identified; (iv) more experimentally supported variant-lncRNA/circRNA-disease/phenotype associations have been manually collected; (v) the sources of lncRNAs, circRNAs, SNPs, somatic mutations and RNA editing sites have been updated. Moreover, four flexible online tools including Genome Browser, Variant Mapper, Circos Plotter and Functional Annotation have been developed to retrieve, visualize and analyze the data. Collectively, LincSNP 3.0 provides associations among functional variants, regulatory elements, lncRNAs and circRNAs in diseases. It will serve as an important and continually updated resource for investigating functions and mechanisms of lncRNAs and circRNAs in diseases.
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http://dx.doi.org/10.1093/nar/gkaa1037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778942PMC
January 2021

Diurnal temperature variations in the lower troposphere as measured by an all-day-operational pure rotational Raman lidar.

Appl Opt 2020 Oct;59(28):8688-8696

We describe a pure rotational Raman lidar for measuring the all-day temperature profiles in the lower troposphere. The lidar is made up of a frequency-tripled Nd:YAG laser at 354.82 nm with ∼250 pulse energy at the 30 Hz repetition rate, a 200 mm receiving telescope, and narrow-band interference-filter-based detection optics. The lidar performance is shown by measured examples. Under clear sky conditions, with an integration time of 60 min and a vertical resolution of 90 m, the 1- statistical uncertainty does not exceed 1 K up to the altitude of ∼4.1 during nighttime, while the corresponding altitude is ∼2.3 at noon. The diurnal temperature variation characteristics have been revealed by the lidar measurements with the 1- statistical uncertainty <1 between altitudes ranging from 0.6 to ∼2.0 at Wuhan, China (30.53°N, 114.37°E). The atmospheric temperature shows a strong diurnal oscillation and moderate semidiurnal oscillation at altitudes 0-1.4 km for two days in July 2019 (July period), 0-1.4 km for four days in September 2019 (September period), and 0-0.8 km for three days in January 2018 (January period), respectively. The mean diurnal and semidiurnal amplitudes of the nine days are respectively ∼1.4 and ∼0.5 at the 0.6 km altitude, while the corresponding surface values are ∼4.2 and ∼1.4, respectively. The diurnal amplitudes tend to weaken with increasing altitude. At altitudes >0.6, the diurnal amplitude in the September period is less than that in the July period, but greater than that in the January period. The phase delays of the diurnal oscillations are ∼3 in the July period, 5-6 h in the September period, and 5-7 h in the January period compared to those at the surface, respectively. Both the diurnal amplitudes and phase delays indicate a possible seasonal dependence.
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http://dx.doi.org/10.1364/AO.394484DOI Listing
October 2020

OxyR controls magnetosome formation by regulating magnetosome island (MAI) genes, iron metabolism, and redox state.

Free Radic Biol Med 2020 12 17;161:272-282. Epub 2020 Oct 17.

State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. Electronic address:

Magnetospirillum gryphiswaldense MSR-1 uses chains of magnetosomes, membrane-enveloped magnetite (Fe(II)Fe(III)O) nanocrystals, to align along magnetic field. The process of magnetosome biomineralization requires a precise biological control of redox conditions to maintain a balanced amounts of ferric and ferrous iron. Here, we identified functions of the global regulator OxyR (MGMSRv2_4250, OxyR-4250) in MSR-1 during magnetosome formation. OxyR deletion mutant ΔoxyR-4250 displayed reduced magnetic response, and increased levels of intracellular ROS (reactive oxygen species). OxyR-4250 protein upregulated expression of six antioxidant genes (ahpC1, ahpC2, katE, katG, sodB, trxA), four iron metabolism-related regulator genes (fur, irrA, irrB, irrC), a bacterioferritin gene (bfr), and a DNA protection gene (dps). OxyR-4250 was shown, for the first time, to directly regulate magnetosome island (MAI) genes mamGFDC, mamXY, and feoAB1 operons. Taken together, our findings indicate that OxyR-4250 helps maintain a proper redox environment for magnetosome formation by eliminating excess ROS, regulating iron homeostasis and participating in regulation of Fe/Fe ratio within the magnetosome vesicle through regulating MAI genes.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.10.015DOI Listing
December 2020

GABC: A comprehensive resource and Genome Atlas for Breast Cancer.

Int J Cancer 2021 02 31;148(4):988-994. Epub 2020 Oct 31.

Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA.

We developed the Genome Atlas of Breast Cancer (GABC), a global map of noncoding events in the human genome associated with breast cancer that provides a valuable reference resource for users to investigate the underlying genome abnormalities in breast cancer patients. Although significant progress has been made in breast cancer treatment, its morbidity and recurrence rates in women are still high worldwide. Curation and integration of breast cancer-related dysregulations from multiple aspects is essential for disease prevention and diagnosis. In this study, we developed the GABC, which contains 10 172 aberrant noncoding events occurring at multiomics levels, including the genome (single nucleotide polymorphism and somatic mutation), transcriptome (long noncoding RNA and microRNA) and epigenome (DNA methylation, enhancer and superenhancer). Each event entry provides descriptions of detailed biological mechanisms specific to the region or element. Users can also check the genome locations and relationships of functional regulators. The GABC provides a flexible and user-friendly interface for users to search, browse and download data. In addition, the GABC provides an interface to submit newly discovered noncoding events that can be included in the database. Therefore, the GABC aims to constantly enhance our understanding of noncoding genomic events in breast cancer.
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http://dx.doi.org/10.1002/ijc.33347DOI Listing
February 2021
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