Publications by authors named "Jinyang Wang"

47 Publications

Synchronous measurement of temperature and deformation by an ultraviolet imaging system and monochromatic pyrometry at extreme temperatures.

Appl Opt 2021 Jul;60(21):6044-6056

Synchronous measurement of temperature and deformation at elevated temperatures is highly critical, yet challenging in evaluating mechanical properties of thermal protection systems. An ultraviolet (UV) imaging system is proposed to obtain noncontact, in situ, synchronous, and full-field temperature and deformation. The established system consists of a monochromatic UV illumination with a bandpass filter for radiation suppressing, a UV CCD camera for image capturing, and an infrared pyrometer for temperature recording. Additionally, an improved monochromatic radiation pyrometry method is proposed, while a deformation measuring method using the UV digital image correlation (UV-DIC) and natural textures-generated speckle is introduced. Furthermore, through camera calibration at room temperature and real-time exposure time adjusted at elevated temperatures, the influence of reflection on radiation pyrometry and unfiltered radiation on DIC analysis is eliminated. Synchronous temperature and deformation fields of C/SiC subjected to flame heating are experimentally measured with a temperature range of 500°C-1500°C, and results demonstrate the efficacy and potential of the proposed system and method. Finally, the importance of exposure time on balancing the light intensity of radiation and reflection is also discussed.
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http://dx.doi.org/10.1364/AO.427281DOI Listing
July 2021

Improving the accuracy of meta-analysis for datasets with missing measures of variance: Elevated [CO] effect on plant growth as a case study.

Sci Total Environ 2022 Feb 28;806(Pt 2):150669. Epub 2021 Sep 28.

Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou 225009, China; Jiangsu Key Laboratory of Crop Genetics and Physiology, Co-Innovation Center for Modern Production Technology of Grain Crops, Yangzhou University, Yangzhou 225009, China. Electronic address:

Ongoing increases in atmospheric carbon dioxide (CO) are expected to stimulate biomass and yield of plants possessing the C3 photosynthetic pathway; however, the extent of stimulation is likely to vary both intra- and inter-species specifically. Meta-analytic approaches can be applied to decrease variation and uncertainty by delineating and characterizing variation, allowing results to be used in modeling plant responses to elevated [CO]. However, the use of meta-analysis in this effort could be limited by missing measures of variance, including standard deviations (SDs) of the compiled dataset. Here, we examined whether there were differences in effect sizes of elevated [CO] on plant growth using various weighting and imputation approaches. Our results showed that the efficacy of different weighting functions and data interpolation methods on meta-analysis outcomes depended on the SDs provided by the studies. Comparing different methodologies for [CO] fumigation as a case study, if the ratio of missing SD was low, the overall trend of effect values and 95% confidence interval (CI) were not changed. For datasets of greenhouse and growth chamber [CO] methodologies, which had a high ratio of missing SDs, effect sizes and 95% confidence intervals using different weighing and imputation methods were influenced relative to that of the raw dataset, with reduced effect sizes and broader CI. Overall these results suggest that application of meta-analysis to discern general biological responses could be influenced by the number of missing SDs. As such, efforts should be made to check the proportion of missing SDs of the compiled dataset and if necessary, to apply various weighting functions and imputation methods to fully discern meta-analysis implications. Our findings could improve the assessment of methodological choices for future [CO] experimentation and discerning long-term trends for agricultural productivity and food security.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150669DOI Listing
February 2022

Difference in an intermolecular disulfide-bond between two highly homologous serum proteins Leg1a and Leg1b implicates their functional differentiation.

Biochem Biophys Res Commun 2021 11 25;579:81-88. Epub 2021 Sep 25.

MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Zebrafish Liver-enriched gene 1a (Leg1a) and Leg1b are liver-produced serum proteins encoded by two adjacently linked homologous genes leg1a and leg1b, respectively. We previously showed that maternal-zygotic (MZ) leg1a null mutant developed a small liver at 3.5 days post-fertilization (dpf) during winter-time or under UV-treatment and displayed an abnormal stature at its adulthood. It is puzzling why Leg1b, which shares 89.3% identity with Leg1a and co-expressed with Leg1a, cannot fully compensate for the loss-of-function of Leg1a in the leg1a MZ mutant. Here we report that Leg1a and Leg1b share eight cysteine residues but differ in amino acid residue 358, which is a serine in Leg1a but cysteine (C) in Leg1b. We find that Leg1b forms an intermolecular disulfide bond through C. Mutating C to Methionine (M) does not affect Leg1b secretion whereas mutating other conserved cysteine residues do. We propose that the intermolecular disulfide bond in Leg1b might establish a rigid structure that makes it functionally different from Leg1a under certain oxidative conditions.
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http://dx.doi.org/10.1016/j.bbrc.2021.09.045DOI Listing
November 2021

Effect of fertilization on nitrogen losses through surface runoffs in Chinese farmlands: A meta-analysis.

Sci Total Environ 2021 Nov 19;793:148554. Epub 2021 Jun 19.

Faculty of Veterinary and Agricultural Sciences, School of Agriculture and Food, The University of Melbourne, VIC 3010, Australia.

Surface runoff is the main cause of farmland nitrogen (N) losses in plain areas, which adversely affect water quality. The impact of fertilization on N runoff loss often varies. A meta-analysis was performed using 245 observations from 31 studies in China, to estimate the response of N loss in both paddy and upland fields subjected to different fertilization strategies, and investigate the link between N runoffs, soil properties, as well as precipitation in the planting season. The results showed that compared to the control (without fertilization), N losses subjected to fertilization increased from 3.31 kg/ha to 10.03 kg/ha and from 3.00 kg/ha to 11.24 kg/ha in paddy and upland fields respectively. Importantly, paddy N loss was significantly correlated with fertilizer type and N application rate (predictors); in upland fields N application rate and seasonal precipitation were the main driving factors. For the N application rate, N loss increased with increase in rates for both paddies and upland fields. Moreover, the N loss from upland fields increased with the precipitation during planting season. Between the three fertilizers used in paddies, the increase in loss of CRF (controlled release fertilizer) or OF (organic fertilizer) was lower than that of CF (inorganic chemical fertilizer) with the lowest value in CRF. Subset analysis showed that the effect of CRF and OF in paddies was not affected by the predictors, revealing the steadily controlling property of CRF and OF in paddies. Also, all the predictors had an insignificant impact to N loss risk in paddies during the high application rate. Overall, the results confirm the importance of N dosage in N runoff loss from farmland. Fertilizer type is a key consideration for N loss control in paddies, while the seasonal precipitation should not be ignored in upland fields.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148554DOI Listing
November 2021

Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis.

Nanomicro Lett 2020 Nov 21;13(1):28. Epub 2020 Nov 21.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, People's Republic of China.

The immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.
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http://dx.doi.org/10.1007/s40820-020-00540-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187671PMC
November 2020

Boosting immune surveillance by low-dose PI3K inhibitor facilitates early intervention of breast cancer.

Am J Cancer Res 2021 15;11(5):2005-2024. Epub 2021 May 15.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center Houston, Texas, USA.

Prevention of estrogen receptor-negative (ER-) breast cancer is an unmet challenge, although tamoxifen and aromatase inhibitors can successfully decrease the incidence of ER-positive (ER+) breast cancer. PI3K pathway activation has been detected in tamoxifen-resistant ER- breast lesions of patients. Here, we further ratified that the PI3K pathway is significantly activated in premalignant ER- breast lesions compared with paired normal tissues of patients, which prompted our assessment of targeting PI3K on inhibition of ER- mammary tumor initiation and progression. Both genetic knockdown of PIK3CA or intervention with low-doses of a PI3K inhibitor (GDC-0941) prevented the dysplasia phenotype of semi-transformed human ER- mammary epithelial cells in 3-dimensional culture . Importantly, low-dose GDC-0941 treatment significantly delayed mammary tumor initiation in the MMTV- mouse model without exhibiting discernable adverse effects. Interestingly, increased CD8/GZMB T-cells were detected in mammary tissue after GDC-0941 treatment, suggesting enhanced immune surveillance. Mechanistically, elevated expression of potent T-cell chemo-attractants, including CCL5 and CXCL10, were detected both and after GDC-0941 treatment. Furthermore, inhibition of PI3K significantly increased T-cell recruitment in a CCL5/CXCL10-dependent manner. In human ER- breast cancer, PI3K activation is correlated with significantly reduced and expression, suggesting that the decreased CD8 T-cell recruitment and escape of immune surveillance may contribute to ER- breast cancer development. In summary, our study indicates that low-dose PI3K inhibitor treatment may intervene early stage ER- breast cancer development by enhancing immune surveillance via CCL5/CXCL10.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167687PMC
May 2021

Highly efficient adsorptive removal of toluene using silicon-modified activated carbon with improved fire resistance.

J Hazard Mater 2021 Aug 26;415:125753. Epub 2021 Mar 26.

National Engineering Laboratory for VOCs Pollution Control Technology and Equipment, School of Environment and Energy, South China University of Technology, Guangzhou 510006, China. Electronic address:

Activated carbons (ACs) are widely applied in the removal of volatile organic compounds (VOCs) emitted from industrial processes, because of their high adsorption capacity, low cost and reusability. Their poor thermal stability under oxidative conditions is a limiting factor and often leads to fire risk in real applications. Here, Si-modification was performed over a wood-derived AC material, and a series of modified ACs with different Si/C mass ratios (0.1-0.9) were prepared via a hydrothermal route. Physicochemical characteristics of Si/C samples was examined by XRD, SEM, TEM, XPS, FTIR and N-physisorption measurements. As compared to pristine AC, Si-modified ACs showed enhanced fire resistance, and an increase of ignition temperature by 79 ℃ was achieved at a Si/C mass ratio of 0.9. A combination of TEM, XPS and FTIR characterization suggests that the formation of amorphous SiO nanoparticles and SiC species on the surface was responsible for the enhanced fire resistance of Si-modified ACs. By increasing microporosity, Si-modification also significantly improved the adsorption capacity of toluene as a model VOC molecule. Static and dynamic adsorption experiments were performed to understand the adsorption kinetics of the Si-modified ACs. Reusability tests showed that the desorption rate of the modified AC remained at nearly 80% even after five cycles of repeated adsorption-desorption, indicating that the modified AC has a great potential for industrial applications.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125753DOI Listing
August 2021

ZEB1 enhances Warburg effect to facilitate tumorigenesis and metastasis of HCC by transcriptionally activating PFKM.

Theranostics 2021 3;11(12):5926-5938. Epub 2021 Apr 3.

The State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

Metabolic reprogramming, especially Warburg effect, is a key event in tumor initiation and progression. ZEB1 plays a vital role in metastasis of various cancers. We previously found that ZEB1 was excessively expressed in hepatocellular carcinoma (HCC) and its high expression was closely correlated with metastasis and recurrence of HCC. We want to know whether glycolytic enzymes are regulated by ZEB1 and contribute to carcinogenesis and metastasis of HCC. To explore whether ZEB1 could enhance glycolysis in HCC, we knocked down ZEB1 by short hairpin RNA (shRNA) in MHCC-97H and HCC-LM3 cells and performed glucose uptake, lactate production, ECAR and OCR assays. To investigate how ZEB1 enhances glycolysis, the protein levels of glycolytic enzymes were detected in the same cell lines using Western blot. The regulatory effect of ZEB1 on PFKM mRNA level was confirmed by RT-qPCR, luciferase report assay and ChIP assay. In order to assess the role of ZEB1-PFKM axis in cell proliferation, cell counting and CCK-8 assays were performed in MHCC-97H and HCC-LM3 cell lines knocked down for ZEB1 and further re-expressed for either ZEB1 or PFKM or not. To explored whether the ZEB1-PFKM axis also functions in HCC cell migration, invasion and metastasis, the same MHCC-97H and HCC-LM3 cell lines were performed for wound healing assays, transwell assays and colony formation assays, meanwhile, MHCC-97H cell lines were performed for orthotopic liver transplantation assays. Finally, the expression of ZEB1 and PFKM were examined in human liver cancer specimens and non-tumorous liver tissues using immunohistochemical and Western blot. We found that ZEB1 transcriptionally upregulates the expression of the muscle isoform of phosphofructokinase-1 (PFKM), a rate-limiting enzyme in glycolysis. Intriguingly, a non-classic ZEB1-binding sequence in the promoter region of PFKM was identified through which ZEB1 directly activates the transcription of PFKM. Silencing of ZEB1 in MHCC-97H and HCC-LM3 cell leads to impaired PFKM expression, glycolysis, proliferation and invasion, and such impairments are rescued by exogenous expression of PFKM. Importantly, HCC xenograft assays and studies from TCGA database demonstrate that ZEB1-PFKM axis is crucial for carcinogenesis and metastasis of HCC. Our study reveals a novel mechanism of ZEB1 in promoting HCC by activating the transcription of PFKM, establishing the direct link of ZEB1 to the promotion of glycolysis and Warburg effect and suggesting that inhibition of ZEB1 transcriptional activity toward PFKM may be a potential therapeutic strategy for HCC.
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http://dx.doi.org/10.7150/thno.56490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058737PMC
July 2021

Individualized plasticity autograft mimic with efficient bioactivity inducing osteogenesis.

Int J Oral Sci 2021 04 12;13(1):14. Epub 2021 Apr 12.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration. At present, autograft harvest procedures may cause secondary trauma to patients, while bone scaffold materials lack osteogenic activity, resulting in a limited application. Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft, but the explosive release of growth factor may also cause side effects. In this study, we innovatively used platelet-rich fibrin (PRF)-modified bone scaffolds (Bio-Oss) to replace autograft, and used cytokine (BMP-2) to enhance osteogenesis. Encouragingly, this mixture, which we named "Autograft Mimic (AGM)", has multiple functions and advantages. (1) The fiber network provided by PRF binds the entire bone scaffold together, thereby shaping the bone grafts and maintaining the space of the defect area. (2) The sustained release of BMP-2 from bone graft promoted bone regeneration continuously. (3) AGM recruited bone marrow mesenchymal stem cells (BMSCs) and promote their proliferation, migration, and osteogenic differentiation. Thus, AGM developed in this study can improve osteogenesis, and provide new guidance for the development of clinical bone grafts.
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http://dx.doi.org/10.1038/s41368-021-00120-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041815PMC
April 2021

Target Reprogramming Lysosomes of CD8+ T Cells by a Mineralized Metal-Organic Framework for Cancer Immunotherapy.

Adv Mater 2021 Apr 24;33(17):e2100616. Epub 2021 Mar 24.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.

T cell immunotherapy holds significant challenges in solid tumors, mainly due to the T cells' low activation and the decreased synthesis-release of therapeutic proteins, including perforin and granzyme B, which are present in lysosomes. In this study, a lysosome-targeting nanoparticle (LYS-NP) is developed by way of a mineralized metal-organic framework (MOF) coupled with a lysosome-targeting aptamer (CD63-aptamer) to enhance the antitumor effect of T cells. The MOF synthesized from Zn and dimethylimidazole has good protein encapsulation and acid sensitivity, and is thus an ideal lysosomal delivery vector. Calcium carbonate (CaCO ) is used to induce MOF mineralization, improve the composite material's stability in encapsulating therapeutic protein, and provide calcium ions with synergistic effects. Before mineralization, perforin and granzyme B-T cell-needed therapeutic proteins for tumors-are preloaded with the MOF. Moreover, T cells are pretreated with processed tumor-specific antigens to activate or produce memory before reprogramming the lysosomes, facilitating the T cell receptor (TCR) for release of the therapeutic proteins. Using T cells recombined by LYS-NPs, a significant enhancement of breast cancer control is confirmed.
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http://dx.doi.org/10.1002/adma.202100616DOI Listing
April 2021

Research and progress on biomarkers of neuromyelitis optica spectrum disorders.

J Recept Signal Transduct Res 2021 Oct 6;41(5):417-424. Epub 2020 Oct 6.

School of Laboratory Medicine, Weifang Medical College, Weifang, P. R. China.

Neuromyelitis optica spectrum disorders (NMOSD) are a demyelinating disorder of the central nervous system based on the involvement of the optic nerve and/or spinal cord. The disease is characterized by high recurrence and disability. NMOSD is mainly diagnosed by AQP4-IgG and MOG-IgG. However, there are still some patients with negative or undetermined double-antibody, and AQP4-IgG and MOG-IgG cannot indicate the clinical disease activity. Therefore, it is urgent to explore interesting biomarkers in serum and cerebrospinal fluid to promote early clinical diagnosis and/or as a target for diagnosis and treatment. This article summarized the research progress in serum and cerebrospinal fluid biomarkers of astrocytes, neurons, myelin sheath, and other damage after the onset of NMOSD. Besides the value of microglial activation-related proteins in the diagnosis and treatment of NMOSD was prospected, so as to promote the research progress of NMOSD.
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http://dx.doi.org/10.1080/10799893.2020.1830109DOI Listing
October 2021

Impact of manure on soil biochemical properties: A global synthesis.

Sci Total Environ 2020 Nov 19;745:141003. Epub 2020 Jul 19.

Department of Soil and Plant Microbiome, Institute of Phytopathology, Christian- Albrecht-University of Kiel, Germany.

Manure application mitigates land degradation and improves soil fertility. Despite many individual studies on manure effects, a comprehensive overview of its consequences for a broad range of soil properties is lacking. Through a meta-analysis of 521 observations spanning the experiments from days after pulse addition up to 113 years with continues manure input, we quantified and generalized the average responses of soil biochemical properties depending on climate factors, management, soil, and manure characteristics. Large increase of pools with fast turnover (microbial carbon (C) and nitrogen (N): +88% and +84%, respectively) compared to stable organic matter pools (+27% for organic C, and +33% for total N) reflects acceleration of C and N cycles and soil fertility improvement. Activities of enzymes acquiring C-, energy-, N-, phosphorus- and sulfur were 1.3-3.3 times larger than those in soil without manure for all study durations included. Soil C/N ratio remained unaffected, indicating the stability of coupled C and N cycles. Microbial C/N ratio decreased, indicating a shift towards bacterial domination, general increase of C and N availability and acceleration of element cycling. Composted manure or manure without mineral fertilizers induced the greatest increase compared to non-composted manure or manure with mineral fertilizers, respectively, in most biochemical properties. The optimal manure application rate for adjusting proper soil pH was 25 Mg ha year. Among manure types, swine manure caused the greatest increase of N-cycle-related properties: microbial N (+230%), urease (+258%) and N-acetyl-β-D-glucosaminidase (+138%) activities. Manure application strategies should avoid P and N losses and pollution via runoff, leaching or gaseous emissions due to fast mineralization and priming of soil organic matter. In conclusion, manure application favors C accumulation and accelerates nutrient cycling by providing available organic substances and nutrients and thus increasing enzyme activities.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141003DOI Listing
November 2020

Increased soil release of greenhouse gases shrinks terrestrial carbon uptake enhancement under warming.

Glob Chang Biol 2020 08 1;26(8):4601-4613. Epub 2020 Jun 1.

Jiangsu Key Laboratory of Low Carbon Agriculture and GHGs Mitigation, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, China.

Warming can accelerate the decomposition of soil organic matter and stimulate the release of soil greenhouse gases (GHGs), but to what extent soil release of methane (CH ) and nitrous oxide (N O) may contribute to soil C loss for driving climate change under warming remains unresolved. By synthesizing 1,845 measurements from 164 peer-reviewed publications, we show that around 1.5°C (1.16-2.01°C) of experimental warming significantly stimulates soil respiration by 12.9%, N O emissions by 35.2%, CH emissions by 23.4% from rice paddies, and by 37.5% from natural wetlands. Rising temperature increases CH uptake of upland soils by 13.8%. Warming-enhanced emission of soil CH and N O corresponds to an overall source strength of 1.19, 1.84, and 3.12 Pg CO -equivalent/year under 1°C, 1.5°C, and 2°C warming scenarios, respectively, interacting with soil C loss of 1.60 Pg CO /year in terms of contribution to climate change. The warming-induced rise in soil CH and N O emissions (1.84 Pg CO -equivalent/year) could reduce mitigation potential of terrestrial net ecosystem production by 8.3% (NEP, 22.25 Pg CO /year) under warming. Soil respiration and CH release are intensified following the mean warming threshold of 1.5°C scenario, as compared to soil CH uptake and N O release with a reduced and less positive response, respectively. Soil C loss increases to a larger extent under soil warming than under canopy air warming. Warming-raised emission of soil GHG increases with the intensity of temperature rise but decreases with the extension of experimental duration. This synthesis takes the lead to quantify the ecosystem C and N cycling in response to warming and advances our capacity to predict terrestrial feedback to climate change under projected warming scenarios.
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http://dx.doi.org/10.1111/gcb.15156DOI Listing
August 2020

Transcriptomic Prediction of Pig Functions in a Liver Cell Line.

Genes (Basel) 2020 04 10;11(4). Epub 2020 Apr 10.

Department of Animal Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.

The newly identified liver-enriched gene 1 () encodes a protein with a characteristic domain of unknown function 781 (DUF781/LEG1), constituting a protein family with only one member in mammals. A functional study in zebrafish suggested that genes are involved in liver development, while the platypus homolog, Monotreme Lactation Protein (), which is enriched in the mammary gland and milk, acts as an antibacterial substance. However, no functional studies on eutherian have been published to date. Thus, we here report the first functional prediction study at the cellular level. As previously reported, eutherian can be classified into three paralogous groups. Pigs have all three genes (), while humans and mice have retained only . Hence, might represent an ideal model for studying gene functions. RNA-seq was performed by the overexpression of and platypus in HepG2 cells. Enrichment analysis showed that and might exhibit little function in liver cells; however, is probably involved in the endoplasmic reticulum (ER) stress response and protein folding. Additionally, gene set enrichment analysis revealed that platypus shows antibacterial activity, confirming the functional study in platypus. Therefore, our study showed from the transcriptomic perspective that mammalian have different functions in liver cells due to the subfunctionalization of paralogous genes.
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http://dx.doi.org/10.3390/genes11040412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230230PMC
April 2020

Transcription factor 7-like 2 promotes osteogenic differentiation and boron-induced bone repair via lipocalin 2.

Mater Sci Eng C Mater Biol Appl 2020 May 15;110:110671. Epub 2020 Jan 15.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China. Electronic address:

Boron-containing mesoporous bioactive glass (B-MBG) scaffolds could be capable of promoting osteogenesis by activating Wnt/β-catenin signaling pathway during the process of bone defect repair. Despite this, more involving molecular controls are still largely unclear. In the present study, we identified that the downstream of Wnt/β-catenin signaling pathway named transcription factor 7-like 2 (TCF7L2) served as a key effector to promote boron-induced bone regeneration and osteogenesis through lipocalin 2 (LCN2). TCF7L2 was highly expressed in osteoblasts when treated with B-MBG scaffold extraction than MBG. LCN2, as a secreted bone factor, positively affected osteogenic differentiation of MC3T3-E1 and osteogenesis in vivo, which could be induced by TCF7L2. In addition, interference of TCF7L2 decreased the osteogenic differentiation of osteoblasts. Finally, we identified that rLCN2 could rescue the poor ability of osteogenic differentiation of MC3T3-E1 whose Tcf7l2 gene was knocked down by lentiviral transfection of shRNA. Our findings provide some new insights into the molecular controls of boron-associated bone regeneration and potential therapeutic targets for the treatment of bone defects.
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http://dx.doi.org/10.1016/j.msec.2020.110671DOI Listing
May 2020

LncRNA CCAT2 promotes the proliferation and invasion of renal cell cancer by sponging miR-320a.

Panminerva Med 2020 Jan 20. Epub 2020 Jan 20.

Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China -

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http://dx.doi.org/10.23736/S0031-0808.19.03778-9DOI Listing
January 2020

Biomimetic anti-inflammatory nano-capsule serves as a cytokine blocker and M2 polarization inducer for bone tissue repair.

Acta Biomater 2020 01 21;102:416-426. Epub 2019 Nov 21.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China. Electronic address:

Controlling of pro-inflammation induced by pro-inflammatory cytokines and anti-inflammatory response induced by M2 macrophages is important for osteogenesis in the process of bone tissue repair. Thus, we fabricated biomimetic anti-inflammatory nano-capsule (BANC) that can block cytokines and promote M2 macrophage polarization, presenting a positive role for bone tissue repair. The BANC is a biomimic nanosystem, coated with lipopolysaccharide-treated macrophage cell membranes with cytokine receptors enveloping gold nanocage (AuNC) as "cytokine blocker", and loaded with resolvin D1 inside into AuNC as "M2 polarization inducer" whose controlled-release could be triggered under near-infrared laser irradiation in sequence, and these chronological events were consistent with the healing process of bone tissue repair. Moreover, in vivo application of femoral bone defects revealed that the BANC composite boron-containing mesoporous bioactive glass scaffolds improved the final effects of bone tissue repair through preventing inflammatory response, promoting M2 polarization in sequence in accord with the in vitro investigation. Hence, cytokine neutralization and M2 macrophage polarization enables the BANC to enhance the bone tissue repair as a biomimetic anti-inflammation effector. Therefore, this study provides potential therapeutic strategies for trauma-mediated or inflammation-related bone defects based on a biomimetic nanomaterial with weakened pro-inflammatory and enhanced anti-inflammatory effects. STATEMENT OF SIGNIFICANCE: Cell membrane-mimic nanomaterials have been popular for blocking natural cell responses for some infection diseases, yet their role in biological process of bone repair is unknown. Here, we fabricated Biomimetic Anti-inflammatory Nano-Capsule (BANC), coated with cell membrane with cytokines receptors on the surface which could neutralize the pro-inflammatory cytokine receptor to block activated pro-inflammation, loaded with Resolvin D1 inside which could be controllably released by NIR irradiation to promote M2 macrophage polarization for the following bone formation during the process of bone repair. Administration of BANC as cytokines blocker and M2 polarization inducer to enhance the bone regeneration, thus presenting a promising potential for the treatment of bone repair and regeneration.
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http://dx.doi.org/10.1016/j.actbio.2019.11.025DOI Listing
January 2020

Anti-inflammation effects of injectable platelet-rich fibrin via macrophages and dendritic cells.

J Biomed Mater Res A 2020 01 3;108(1):61-68. Epub 2019 Sep 3.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Immune response to implantation materials plays a critical role during early local inflammation and biomaterial-induced regeneration or restoration. A novel platelet concentrate termed i-PRF (injectable platelet-rich fibrin) has recently been developed without any additives by low centrifugation speeds. To date, scientists have investigated the capability of releasing growth factors to improve regeneration but have ignored whether i-PRF can inhibit the inflammatory effect around the wound. The present study investigated the anti-inflammation effects of i-PRF on immune response-related cells, especially macrophages and dendric cells. We found that i-PRF reduced pro-inflammatory M1 phenotype of macrophages and activated dendritic cells around muscle defect that was injected with bacterial suspension. Moreover, in vitro experiments showed similar results. i-PRF deleted inflammatory response caused by lipopolysaccharide to some extent. We determined that TLR4, an activator of inflammatory stimulation and p-p65, a key factor belongs to classical inflammatory related NF-κB signal pathway, can be inhibited by use of i-PRF. Results indicate the potential anti-inflammatory role of i-PRF during regeneration and restoration.
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http://dx.doi.org/10.1002/jbm.a.36792DOI Listing
January 2020

Near-Infrared Light-Sensitive Nano Neuro-Immune Blocker Capsule Relieves Pain and Enhances the Innate Immune Response for Necrotizing Infection.

Nano Lett 2019 09 9;19(9):5904-5914. Epub 2019 Aug 9.

State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology , Wuhan University , Wuhan 430079 , China.

Sensory neurons promote profound suppressive effects on neutrophils during infection and contribute to the pathogenesis of necrotizing infection ("flesh-eating disease"). Thus, the development of new antibacterial agents for necrotizing infection is promising because of the clear streptococcal neuro-immune communication. Herein, based on the immune escape membrane exterior and competitive membrane functions of the glioma cell membrane, a novel nano neuro-immune blocker capsule was designed to prevent neuronal activation and improve neutrophil immune responses for necrotizing infection. These nano neuro-immune blockers could neutralize streptolysin S, suppress neuron pain conduction and calcitonin gene-related peptide release, and recruit neutrophils to the infection site, providing a strong therapeutic effect against necrotizing infection. Furthermore, nano neuro-immune blockers could serve as an effective inflammatory regulator and antibacterial agent via photothermal effects under near-infrared irradiation. In the -induced necrotizing fasciitis mouse model, nano neuro-immune blockers showed significant therapeutic efficacy by ameliorating sensitivity to pain and promoting the antibacterial effect of neutrophils.
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http://dx.doi.org/10.1021/acs.nanolett.9b01459DOI Listing
September 2019

Transcription factor 7-like 2-associated signaling mechanism in regulating cementum generation by the NF-κB pathway.

J Cell Physiol 2019 11 29;234(11):20790-20800. Epub 2019 Apr 29.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Cementum regeneration is an important and challenging stage in periodontal tissue engineering and regeneration. Pathosis of the periodontium, including cementum, is important in precision diagnosis and obstinate treatment of systemic diseases, such as diabetes, leukemia, and Acquired Immune Deficiency Syndrome. Here, we found that during periodontium development, transcription factor 7-like 2 (Tcf7l2) was widely expressed in the periodontium and dental sac. In mouse cementoblast cell line (OCCM-30), the activation of NF-κB and cementoblast mineralization was significantly reduced when Tcf7l2 gene was silenced. Moreover, Tcf7l2 has a positive effect on NF-κB and cementoblast mineralization. Therefore, Tcf7l2 promotes cementum formation through the NF-κB pathway. In addition, we found a decreased expression of phosphorylated p65 and a thin layer of cementum in Tcf7l2 mice. These results suggest that Tcf7l2, which accelerates cementum formation by activating NF-κB, has great potential in the treatment of periodontitis and provide guidance for periodontal tissue regeneration.
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http://dx.doi.org/10.1002/jcp.28685DOI Listing
November 2019

Genome-wide association study of inflorescence length of cultivated soybean based on the high-throughout single-nucleotide markers.

Mol Genet Genomics 2019 Jun 9;294(3):607-620. Epub 2019 Feb 9.

Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.

As an important and complex trait, inflorescence length (IL) of soybean [Glycine max (L.) Merr.] significantly affected seed yields. Therefore, elucidating molecular basis of inflorescence architecture, especially for IL, was important for improving soybean yield potentials. Longer IL meaned to have more pod and seed in soybean. Hence, increasing IL and improving yield are targets for soybean breeding. In this study, a association panel, comprising 283 diverse samples, was used to dissect the genetic basis of IL based on genome-wide association analysis (GWAS) and haplotype analysis. GWAS and haplotype analysis were conducted through high-throughout single-nucleotide polymorphisms (SNP) developed by SLAF-seq methodology. A total of 39, 057 SNPs (minor allele frequency ≥ 0.2 and missing data ≤ 10%) were utilized to evaluate linkage disequilibrium (LD) level in the tested association panel. A total of 30 association signals were identified to be associated with IL via GWAS. Among them, 13 SNPs were novel, and another 17 SNPs were overlapped or located near the linked regions of known quantitative trait nucleotide (QTN) with soybean seed yield or yield component. The functional genes, located in the 200-kb genomic region of each peak SNP, were considered as candidate genes, such as the cell division/ elongation, specific enzymes, and signaling or transport of specific proteins. These genes have been reported to participant in the regulation of IL. Ten typical long-IL lines and ten typical short-IL lines were re-sequencing, and then, six SNPs from five genes were obtained based on candidate gene-based association. In addition, 42 haplotypes were defined based on haplotype analysis. Of them, 11 haplotypes were found to regulate long IL (> 14 mm) in soybean. The identified 30 QTN with beneficial alleles and their candidate genes might be valuable for dissecting the molecular mechanisms of IL and further improving the yield potential of soybean.
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http://dx.doi.org/10.1007/s00438-019-01533-3DOI Listing
June 2019

Effects of four years of elevated ozone on microbial biomass and extracellular enzyme activities in a semi-natural grassland.

Sci Total Environ 2019 Apr 7;660:260-268. Epub 2019 Jan 7.

School of Natural Sciences, Environment Centre Wales, Bangor University, Bangor, Gwynedd LL57 2UW, UK; UWA School of Agriculture and Environment, University of Western Australia, Crawley, WA 6009, Australia.

Reduced belowground carbon (C) allocation by plants exposed to ozone may change properties and activities of the microbial community in soils. To investigate how soil microbial biomass and extracellular enzyme activities respond to elevated ozone, we collected soils from a temperate grassland after four years of ozone exposure under fully open-air field conditions. We measured soil microbial biomass, the metabolism of low molecular weight C substrates and hydrolytic extracellular enzyme activities in both bulk soil and isolated aggregates to assess changes in microbial activity and community function. After four years of elevated ozone treatment, soil total organic C was reduced by an average of 20% compared with ambient condition. Elevated ozone resulted in a small but insignificant reduction (4-10%) in microbial biomass in both bulk soil and isolated aggregates. Activities of extracellular enzymes were generally not affected by elevated ozone, except β-glucosidase, whose activity in bulk soil was significantly lower under elevated ozone than ambient condition. Activities of β-glucosidase, leucine aminopeptidase and acid phosphatase were higher in microaggregates (<0.25 mm) as compared to macroaggregates (>0.25 mm). Elevated ozone had no effects on mineralization rates of low molecular weight C substrates in both bulk soil and isolated aggregates. We therefore conclude that the size and activity rather than function of the soil microbial community in this semi-natural grassland are altered by elevated ozone.
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http://dx.doi.org/10.1016/j.scitotenv.2019.01.040DOI Listing
April 2019

Identification of the Genomic Region Underlying Seed Weight per Plant in Soybean ( L. Merr.) via High-Throughput Single-Nucleotide Polymorphisms and a Genome-Wide Association Study.

Front Plant Sci 2018 11;9:1392. Epub 2018 Oct 11.

Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, China.

Seed weight per plant (SWPP) of soybean ( (L.) Merr.), a complicated quantitative trait controlled by multiple genes, was positively associated with soybean seed yields. In the present study, a natural soybean population containing 185 diverse accessions primarily from China was used to analyze the genetic basis of SWPP via genome-wide association analysis (GWAS) based on high-throughput single-nucleotide polymorphisms (SNPs) generated by the Specific Locus Amplified Fragment Sequencing (SLAF-seq) method. A total of 33,149 SNPs were finally identified with minor allele frequencies (MAF) > 5% which were present in 97% of all the genotypes. Twenty association signals associated with SWPP were detected via GWAS. Among these signals, eight SNPs were novel loci, and the other twelve SNPs were overlapped or located in the linked genomic regions of the reported QTL from SoyBase database. Several genes belonging to the categories of hormone pathways, RNA regulation of transcription in plant development, ubiquitin, transporting systems, and other metabolisms were considered as candidate genes associated with SWPP. Furthermore, nine genes from the flanking region of Gm07:19488264, Gm08:15768591, Gm08:15768603, or Gm18:23052511 were significantly associated with SWPP and were stable among multiple environments. Nine out of 18 haplotypes from nine genes showed the effect of increasing SWPP. The identified loci along with the beneficial alleles and candidate genes could be of great value for studying the molecular mechanisms underlying SWPP and for improving the potential seed yield of soybean in the future.
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http://dx.doi.org/10.3389/fpls.2018.01392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194254PMC
October 2018

Rho A Regulates Epidermal Growth Factor-Induced Human Osteosarcoma MG63 Cell Migration.

Int J Mol Sci 2018 May 11;19(5). Epub 2018 May 11.

Department of Anatomy, Guangdong Provincial Key Laboratory of Tissue Construction and Detection, Southern Medical University, Guangzhou 510515, China.

Osteosarcoma, the most common primary bone tumor, occurs most frequently in children and adolescents and has a 5-year survival rate, which is unsatisfactory. As epidermal growth factor receptor (EGFR) positively correlates with TNM (tumor-node-metastasis) stage in osteosarcoma, EGFR may play an important role in its progression. The purpose of this study was to explore potential mechanisms underlying this correlation. We found that EGF promotes MG63 cell migration and invasion as well as stress fiber formation via Rho A activation and that these effects can be reversed by inhibiting Rho A expression. In addition, molecules downstream of Rho A, including ROCK1, LIMK2, and Cofilin, are activated by EGF in MG63 cells, leading to actin stress fiber formation and cell migration. Moreover, inhibition of ROCK1, LIMK2, or Cofilin in MG63 cells using known inhibitors or short hairpin RNA (shRNA) prevents actin stress fiber formation and cell migration. Thus, we conclude that Rho A/ROCK1/LIMK2/Cofilin signaling mediates actin microfilament formation in MG63 cells upon EGFR activation. This novel pathway provides a promising target for preventing osteosarcoma progression and for treating this cancer.
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http://dx.doi.org/10.3390/ijms19051437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983621PMC
May 2018

IDH1 Arg-132 mutant promotes tumor formation through down-regulating p53.

J Biol Chem 2018 06 9;293(25):9747-9758. Epub 2018 May 9.

From the State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China,

Resistance to apoptosis and uncontrolled proliferation are two hallmarks of cancer cells. p53 is crucial for apoptosis triggered by a broad range of stresses and a well-known gatekeeper for neoplastic transformation. Here we show that oncogenic IDH1 R132H/R132Q mutants robustly inhibit p53 expression and such an effect is attributed to 2-HG production. Mechanistically, 2-hydroxyglutarate (2-HG) stabilizes hypoxia-inducible factor-2α, which in turn activates the expression of miR-380-5p, a characterized microRNA against p53 expression. Rescue expression of p53 can inhibit the proliferation rate and impair the resistance of apoptosis induced by doxorubicin in IDH1 R132Q mouse embryonic fibroblast cells. Furthermore, p53 protein levels correlates negatively with IDH1 R132H levels in human glioma samples. Our results thus shed a new light on how p53 is down-regulated by 2-HG and suggests that impairment of p53-mediated apoptosis contributes to the tumorigenesis driven by IDH1 mutants.
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http://dx.doi.org/10.1074/jbc.RA117.001385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016470PMC
June 2018

Angiotensin II receptor blocker valsartan ameliorates cardiac fibrosis partly by inhibiting miR-21 expression in diabetic nephropathy mice.

Mol Cell Endocrinol 2018 09 9;472:149-158. Epub 2017 Dec 9.

Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin, 300070, PR China.

Cardiac fibrosis with diabetic nephropathy (DN) is one of major diabetic complications. miR-21 and MMP-9 were closely associated with fibrosis diseases. Angiotensin II receptor blockers (ARB) have cardioprotective effects. However, it remains unclear whether miR-21 was involved in the mechanism of cardiac fibrosis with DN by target MMP-9 and ARB ameliorates cardiac fibrosis partly by inhibiting miR-21 expression. In this study, In Situ Hybridization(ISH), RT-PCR, cell transfection, western blotting and laser confocal telescope were used, respectively. ISH showed that miR-21, concentrated in cytoplasmic foci in the proximity of the nucleus, was mainly localized in cardiac fibroblasts and at relatively low levels in cardiomyocytes within cardiac tissue with DN. RT-PCR showed that miR-21 expression was significantly enhanced in cardiac tissue with DN, accompanied by the increase of col-IV, FN, CVF, PVCA, LVMI, HWI and NT-pro-BNP (p < 0.05). Bioinformatics analysis and Luciferase reporter gene assays showed that MMP-9 was a validated target of miR-21. Furthermore, cell transfection experiments showed that miR-21 overexpression directly decreased MMP-9 expression. Interestingly, miR-21 levels in cardiac tissue was positively correlated with ACR (r = -0.870, P = 0.003), whereas, uncorrelated with SBP, HbA1C and T-Cho (p > 0.05). More importantly, ARB can significantly decrease miR-21 expression in cardiac tissue, cardiac fibroblasts and serum. Overall, our results suggested that miR-21 may contribute to the pathogenesis of cardiac fibrosis with DN by target MMP-9, and that miR-21 may be a new possible therapeutic target for ARB in cardiac fibrosis with DN.
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http://dx.doi.org/10.1016/j.mce.2017.12.005DOI Listing
September 2018

Metformin ameliorates skeletal muscle insulin resistance by inhibiting miR-21 expression in a high-fat dietary rat model.

Oncotarget 2017 Nov 24;8(58):98029-98039. Epub 2017 Aug 24.

Department of Endocrinology, Beijing Tongren hospital of Capital Medical University, Beijing, China.

Insulin resistance (IR) plays a major role in the pathogenesis of abdominal obesity, hypertension, coronary heart disease, atherosclerosis and diabetes. miR-21 and TGF-β/smads is closely related to IR. However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-β1/smads expression. In this study, high-fat diet rats with IR model and IR-skeletal muscle L6 cells (L6-SMCs) model were established, insulin sensitive index (ISI) and Homeostasis model assessment of IR (HOMA-IR) were applied, miR-21 and TGF-β1/smads mRNA expression were examined by RT-PCR, smad3 and smad7 protein were detected by western-blotting and laser scanning confocal microscopy (LSCM), the valid target of miR-21 was detected by luciferase reporter gene assay. Here, we found that metformin dose-dependently decreased miR-21 expression, accompanied by the decrease of HOMA-IR and the increase of HOMA-ISI. Luciferase report gene assay showed that smad7 was an effective target of miR-21. miR-21 overexpression directly downregulated smad7 and indirectly upregulated smad3 expression. Interestingly, miR-21 expression positively correlated with HOMA-IR and negatively correlated with HOMA-ISI. In conclusion, our results demonstrated that metformin improved IRSM by inhibiting miR-21 expression, and that miR-21 may be one of the therapeutic targets for IR.
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http://dx.doi.org/10.18632/oncotarget.20442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716711PMC
November 2017

14-3-3ζ loss leads to neonatal lethality by microRNA-126 downregulation-mediated developmental defects in lung vasculature.

Cell Biosci 2017 2;7:58. Epub 2017 Nov 2.

Department of Molecular and Cellular Oncology, Unit 108, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 USA.

Background: The 14-3-3 family of proteins have been reported to play an important role in development in various mouse models, but the context specific developmental functions of 14-3-3ζ remain to be determined. In this study, we identified a context specific developmental function of 14-3-3ζ.

Results: Targeted deletion of 14-3-3ζ in the C57Bl/6J murine genetic background led to neonatal lethality due to respiratory distress and could be rescued by out-breeding to the CD-1 or backcrossing to the FVB/NJ congenic background. Histological analysis of lung sections from 18.5 days post coitum embryos (dpc) showed that 14-3-3ζ-/- lung development is arrested at the pseudoglandular stage and exhibits vascular defects. The expression of miR-126, an endothelial-specific miRNA known to regulate lung vascular integrity was down-regulated in the lungs of the 14-3-3ζ-/- embryos in the C57Bl/6J background as compared to their wild-type counterparts. Loss of 14-3-3ζ in endothelial cells inhibited the angiogenic capability of the endothelial cells as determined by both trans-well migration assays and tube formation assays and these defects could be rescued by re-expressing miR-126. Mechanistically, loss of 14-3-3ζ led to reduced Erk1/2 phosphorylation resulting in attenuated binding of the transcription factor Ets2 on the miR-126 promoter which ultimately reduced expression of miR-126.

Conclusion: Our data demonstrates that miR-126 is an important angiogenesis regulator that functions downstream of 14-3-3ζ and downregulation of miR-126 plays a critical role in 14-3-3ζ-loss induced defects in lung vasculature in the C57Bl/6J genetic background.
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http://dx.doi.org/10.1186/s13578-017-0186-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667492PMC
November 2017

Global analysis of agricultural soil denitrification in response to fertilizer nitrogen.

Sci Total Environ 2018 Mar 28;616-617:908-917. Epub 2017 Oct 28.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, People's Republic of China. Electronic address:

Terrestrial soil denitrification is of great importance for closing the nitrogen (N) cycle, yet the current understanding of soil denitrification response to N fertilization remains uncertain. While there has been a focus on factors controlling NO fluxes from agricultural soils because of its global warming effect, much less is known about factors controlling total denitrification losses, yet these can be sufficiently large to affect N use efficiency. Here, we collated 353 observations from 74 papers and conducted a global-scale meta-analysis to explore the effects of N fertilization on agricultural soil denitrification (NO+N) where the acetylene inhibition technique was used. Relative to the control, N fertilization significantly increased soil denitrification by an average of 174%, although the magnitude of this increase differed significantly across environmental and soil conditions. Soil denitrification was more responsive to N fertilization in grasslands than in croplands. The changes in soil denitrification increased exponentially when the rates of synthetic N fertilizer application≤250kgNha, but above this threshold, there were no further increases. The responses of soil denitrification to N fertilization were negatively correlated with soil clay content, C:N ratio, and bulk density. The comparable responses of soil NO emissions (165%) and denitrification to N fertilization resulted in a small insignificant decrease of the NO:N ratio. Organic fertilizer applied with and without synthetic N fertilizer can contribute to lower NO emissions probably by facilitating the last step of soil denitrification to N production. Taken together, we conclude that these findings can provide important insights on regulating soil denitrification, which might contribute to improvement of N use efficiency and elimination of its negative impacts in agro-ecosystems.
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http://dx.doi.org/10.1016/j.scitotenv.2017.10.229DOI Listing
March 2018

Targeting Aberrant p70S6K Activation for Estrogen Receptor-Negative Breast Cancer Prevention.

Cancer Prev Res (Phila) 2017 Nov 6;10(11):641-650. Epub 2017 Sep 6.

Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.

The prevention of estrogen receptor-negative (ER-) breast cancer remains a major challenge in the cancer prevention field, although antiestrogen and aromatase inhibitors have shown adequate efficacy in preventing estrogen receptor-positive (ER) breast cancer. Lack of commonly expressed, druggable targets is a major obstacle for meeting this challenge. Previously, we detected the activation of Akt signaling pathway in atypical hyperplasic early-stage lesions of patients. In the current study, we found that Akt and the downstream 70 kDa ribosomal protein S6 kinase (p70S6K) signaling pathway was highly activated in ER premalignant breast lesions and ER breast cancer. In addition, p70S6K activation induced transformation of ER human mammary epithelial cells (hMEC). Therefore, we explored the potential of targeting Akt/p70S6K in the p70S6K activated, ER hMEC models and mouse mammary tumor models for the prevention of ER breast cancer. We found that a clinically applicable Akt/p70S6K dual inhibitor, LY2780301, drastically decreased proliferation of hMECs with ErbB2-induced p70S6K activation via Cyclin B1 inhibition and cell-cycle blockade at G-G phase, while it did not significantly reverse the abnormal acinar morphology of these hMECs. In addition, a brief treatment of LY2780301 in MMTV- mice that developed atypical hyperplasia (ADH) and mammary intraepithelial neoplasia (MIN) lesions with activated p70S6K was sufficient to suppress S6 phosphorylation and decrease cell proliferation in hyperplasic MECs. In summary, targeting the aberrant Akt/p70S6K activation in ER hMEC models and in the MMTV- transgenic mouse model effectively inhibited Akt/S6K signaling and reduced proliferation of hMECs and ADH/MIN lesions , indicating its potential in prevention of p70S6K activated ER breast cancer. .
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http://dx.doi.org/10.1158/1940-6207.CAPR-17-0106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668174PMC
November 2017
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