Publications by authors named "Ronggui Hu"

79 Publications

OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis.

Adv Sci (Weinh) 2021 May 29:e2004504. Epub 2021 May 29.

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

Genomic amplification of OTUD7B is frequently found across human cancers. But its role in tumorigenesis is poorly understood. Lysine-specific demethylase 1 (LSD1) is known to execute epigenetic regulation by forming corepressor complex with CoREST/histone deacetylases (HDACs). However, the molecular mechanisms by which cells maintain LSD1/CoREST complex integrity are unknown. Here, it is reported that LSD1 protein undergoes K63-linked polyubiquitination. OTUD7B is responsible for LSD1 deubiquitination at K226/277 residues, resulting in dynamic control of LSD1 binding partner specificity and cellular homeostasis. OTUD7B deficiency increases K63-linked ubiquitination of LSD1, which disrupts LSD1/CoREST complex formation and targets LSD1 for p62-mediated proteolysis. Consequently, OTUD7B deficiency impairs genome-wide LSD1 occupancy and enhances the methylation of H3K4/H3K9, therefore profoundly impacting global gene expression and abrogating breast cancer metastasis. Moreover, physiological fluctuation of OTUD7B modulates cell cycle-dependent LSD1 oscillation, ensuring the G1/S transition. Both OTUD7B and LSD1 proteins are overpresented in high-grade or metastatic human breast cancer, while dysregulation of either protein is associated with poor survival and metastasis. Thus, OTUD7B plays a unique partner-switching role in maintaining the integrity of LSD1/CoREST corepressor complex, LSD1 turnover, and breast cancer metastasis.
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http://dx.doi.org/10.1002/advs.202004504DOI Listing
May 2021

Epilepsy-Associated UBE3A Deficiency Downregulates Retinoic Acid Signalling Pathway.

Front Genet 2021 28;12:681295. Epub 2021 Apr 28.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

Ubiquitin-protein ligase E3A (UBE3A) has dual functions as a E3 ubiquitin-protein ligase and coactivator of nuclear hormone receptors. Mutations or deletions of the maternally inherited UBE3A gene cause Angelman syndrome. Here, we performed transcriptome profiling in the hippocampus of and mice, and determined that the expression of the retinoic acid (RA) signalling pathway was downregulated in Ube3a-deficient mice compared to WT mice. Furthermore, we demonstrated that UBE3A directly interacts with RARα and may function as a coactivator of the nuclear receptor RARα to participate in the regulation of gene expression. Loss of UBE3A expression caused the downregulation of the expression of RA-related genes, including , and in Ube3a mice brain tissues. This work revealed a new role for UBE3A in regulating retinoic acid (RA) signalling downstream genes and hopefully to shed light on the potential drug target of AS.
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http://dx.doi.org/10.3389/fgene.2021.681295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113777PMC
April 2021

Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels.

J Biol Chem 2021 May 3:100738. Epub 2021 May 3.

Division of Life Science, Hong Kong University of Science and Technology, Hong Kong; Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Hong Kong; State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong; HKUST Shenzhen Research Institute, Hong Kong University of Science and Technology, Hong Kong; Hong Kong Branch of Guangdong Southern Marine Science and Engineering Laboratory (Guangzhou), Hong Kong University of Science and Technology, Hong Kong. Electronic address:

ANO1 (TMEM16A) is a calcium-activated chloride channel that plays critical roles in diverse physiological processes, such as sensory transduction and epithelial secretion. ANO1 levels have been shown to be altered under physiological and pathological conditions, although the molecular mechanisms that control ANO1 protein levels remain unclear. The ubiquitin-proteasome system is known to regulate the levels of numerous ion channels, but little information is available regarding whether and how ubiquitination regulates levels of ANO1. Here, we showed that two E3 ligases, TRIM23 and TRIM21, physically interact with the C-terminus of ANO1. In vitro and in vivo assays demonstrated that whereas TRIM23 ubiquitinated ANO1 leading to its stabilization, TRIM21 ubiquitinated ANO1 and induced its degradation. Notably, ANO1 regulation by TRIM23 and TRIM21 is involved in chemical-induced pain sensation, salivary secretion, and heart-rate control in mice, and TRIM23 also mediates ANO1 upregulation induced by epidermal growth factor (EGF) treatment. Our results suggest that these two antagonistic E3 ligases act together to control ANO1 expression and function. Our findings reveal a previously unrecognized mechanism for regulating ANO1 protein levels and identify a potential molecular link between ANO1 regulation, EGF, and other signaling pathways.
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http://dx.doi.org/10.1016/j.jbc.2021.100738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191318PMC
May 2021

RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation.

Blood 2021 Apr 25. Epub 2021 Apr 25.

Zhejiang University School of Medicine, Hangzhou, China.

Ferroportin (FPN), the body's sole iron exporter, is essential for maintaining systemic iron homeostasis. In response to either increased iron or inflammation, hepatocyte-secreted hepcidin binds to FPN, inducing its internalization and subsequent degradation. However, the E3 ubiquitin ligase that underlies FPN degradation has not been identified. Here, we report the identification and characterization of a novel mechanism involving the RNF217-mediated degradation of FPN. A combination of two different E3 screens revealed that the Rnf217 gene is a target of Tet1, mediating the ubiquitination and subsequent degradation of FPN. Interestingly, loss of Tet1 expression causes an accumulation of FPN and an impaired response to iron overload, manifested by increased iron accumulation in the liver together with decreased iron in the spleen and duodenum. Moreover, we found that the degradation and ubiquitination of FPN could be attenuated by mutating RNF217. Finally, using two conditional knockout mouse lines, we found that knocking out Rnf217 in macrophages increases splenic iron export by stabilizing FPN, whereas knocking out Rnf217 in intestinal cells appears to increase iron absorption. These findings suggest that the Tet1-RNF217-FPN axis regulates iron homeostasis, revealing new therapeutic targets for FPN-related diseases.
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http://dx.doi.org/10.1182/blood.2020008986DOI Listing
April 2021

MKRN3-mediated ubiquitination of Poly(A)-binding proteins modulates the stability and translation of GNRH1 mRNA in mammalian puberty.

Nucleic Acids Res 2021 04;49(7):3796-3813

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.

The family of Poly(A)-binding proteins (PABPs) regulates the stability and translation of messenger RNAs (mRNAs). Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC). Recently, we have shown that MKRN3 epigenetically regulates the transcription of GNRH1 through conjugating poly-Ub chains onto methyl-DNA bind protein 3 (MBD3). Therefore, MKRN3-mediated ubiquitin signalling could control both transcriptional and post-transcriptional switches of mammalian puberty initiation. While identifying MKRN3 as a novel tissue-specific translational regulator, our work also provided new mechanistic insights into the etiology of MKRN3 dysfunction-associated human CPP.
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http://dx.doi.org/10.1093/nar/gkab155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053111PMC
April 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Translatomic profiling reveals novel self-restricting virus-host interactions during HBV infection.

J Hepatol 2021 Jul 20;75(1):74-85. Epub 2021 Feb 20.

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200031, China; School of Life Science, Hangzhou Institute for Advance Study, University of Chinese Academy of Sciences, Hangzhou 310024, China. Electronic address:

Background & Aims: HBV remains a global threat to human health. It remains incompletely understood how HBV self-restricts in the host during most adult infections. Thus, we performed multi-omics analyses to systematically interrogate HBV-host interactions and the life cycle of HBV.

Methods: RNA-sequencing and ribosome profiling were conducted with cell-based models for HBV replication and gene expression. The novel translational events or products hereby detected were then characterized, and functionally assessed in both cell and mouse models. Moreover, quasi-species analyses of HBV subpopulations were conducted with patients at immune tolerance or activation phases, using next- or third-generation sequencing.

Results: We identified EnhI-SL (Enhancer I-stem loop) as a new cis element in the HBV genome; mutations disrupting EnhI-SL were found to elevate viral polymerase expression. Furthermore, while re-discovering HpZ/P', a previously under-explored isoform of HBV polymerase, we also identified HBxZ, a novel short isoform of HBX. Having confirmed their existence, we functionally characterized them as potent suppressors of HBV gene expression and genome replication. Mechanistically, HpZ/P' was found to repress HBV gene expression partially by interacting with, and sequestering SUPV3L1. Activation of the host immune system seemed to reduce the abundance of HBV mutants deficient in HpZ/P' or with disruptions in EnhI-SL. Finally, SRSF2, a host RNA spliceosome protein that is downregulated by HBV, was found to promote the splicing of viral pre-genomic RNA and HpZ/P' biogenesis.

Conclusion: This study has identified multiple self-restricting HBV-host interactions. In particular, SRSF2-HpZ/P' appeared to constitute another negative feedback mechanism in the HBV life cycle. Targeting host splicing machinery might thus represent a strategy to intervene in HBV-host interactions.

Lay Summary: There remain many unknowns about the natural history of HBV infection in adults. Herein, we identified new HBV-host mechanisms which could be responsible for self-restricting infections. Targeting these mechanisms could be a promising strategy for the treatment of HBV infections.
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http://dx.doi.org/10.1016/j.jhep.2021.02.009DOI Listing
July 2021

A Novel Prognostic Model of Early-Stage Lung Adenocarcinoma Integrating Methylation and Immune Biomarkers.

Front Genet 2020 21;11:634634. Epub 2021 Jan 21.

Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai, China.

Lung adenocarcinoma (LUAD) is caused by multiple biological factors. Therefore, it will be more meaningful to study the prognosis from the perspective of omics integration. Given the significance of epigenetic modification and immunity in tumorigenesis and development, we tried to combine aberrant methylation and tumor infiltration CD8 T cell-related genes to build a prognostic model, to explore the key biomarkers of early-stage LUAD. On the basis of RNA-seq and methylation microarray data downloaded from The Cancer Genome Atlas (TCGA), differentially expressed genes and aberrant methylated genes were calculated with "DEseq2" and "ChAMP" packages, respectively. A Chi-square test was performed to obtain methylation driver genes. Weighted correlation network analysis (WGCNA) was utilized to mine cancer biomarkers related to CD8 T cells. With the consequences of univariate Cox proportional hazards analysis and least absolute shrinkage and selection operator (LASSO) COX regression analysis, the prognostic index based on 17 methylation driver genes (ZNF677, FAM83A, TRIM58, CLDN6, NKD1, NFE2L3, FKBP5, ITGA5, ASCL2, SLC24A4, WNT3A, TMEM171, PTPRH, ITPKB, ITGA2, SLC6A17, and CCDC81) and four CD8 T cell-related genes (SPDL1, E2F7, TK1, and TYMS) was successfully established, which could make valuable predictions for the survival risk of patients with early-stage LUAD.
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http://dx.doi.org/10.3389/fgene.2020.634634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859522PMC
January 2021

Five-year soil warming changes soil C and N dynamics in a single rice paddy field in Japan.

Sci Total Environ 2021 Feb 20;756:143845. Epub 2020 Nov 20.

Tohoku Agricultural Research Center, NARO, 4 Akahira, Shimokuriyagawa, Morioka 020-0198, Japan.

Soil temperature is an important determinant of carbon (C) and nitrogen (N) cycling in terrestrial ecosystems, but its effects on soil organic carbon (SOC) and total nitrogen (TN) dynamics as well as rice biomass in rice paddy ecosystems are not fully understood. We conducted a five-year soil warming experiment in a single-cropping paddy field in Japan. Soil temperatures were elevated by approximate 2 °C with heating wires during the rice growing season and by approximate 1 °C with nighttime thermal blankets during the fallow season. Soil samples were collected in autumn after rice harvest and in spring after fallow each year, and anaerobically incubated at 30 °C for four weeks to determine soil C decomposition and N mineralization potentials. The SOC and TN contents, rice biomass, dissolved organic carbon (DOC) and microbial biomass carbon (MBC) concentrations were measured in the study. Soil warming did not significantly enhance rice aboveground and root biomasses, but it significantly decreased SOC and TN contents and thus decreased soil C decomposition and N mineralization potentials due to depletion of available C and N. Moreover, soil warming significantly decreased DOC concentration but significantly increased MBC concentration. The ratios of C decomposition potential to N mineralization potential, decomposition potential to SOC, and N mineralization to TN were not affected by soil warming. There were significant seasonal and annual variations in SOC, C decomposition and N mineralization potentials, soil DOC and MBC under each temperature treatments. Our study implied that soil warming can decrease soil C and N stocks in paddy ecosystem probably via stimulating microbial activities and accelerating the depletion of DOC. This study further highlights the importance of long-term in situ observation of C and N dynamics and their availabilities in rice paddy ecosystems under increasing global warming scenarios.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143845DOI Listing
February 2021

Screening for bacterial enzymes synthesizing GPR119 agonist in cAMP-responsive cells.

Acta Biochim Biophys Sin (Shanghai) 2021 Jan;53(1):121-123

Guizhou University School of Medicine, Guiyang 550025, China.

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http://dx.doi.org/10.1093/abbs/gmaa144DOI Listing
January 2021

Clinical and molecular characterization of thirty Chinese patients with congenital lipoid adrenal hyperplasia.

J Steroid Biochem Mol Biol 2021 02 20;206:105788. Epub 2020 Nov 20.

Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 200025, China. Electronic address:

Congenital lipoid adrenal hyperplasia (LCAH), as the most severe form of congenital adrenal hyperplasia (CAH), is caused by mutations in the steroidogenic acute regulatory protein (STAR). Affected patients were typically characterized by adrenal insufficiency in the first year of life and present with female external genitalia regardless of karyotype. Non-classic LCAH patients usually present from 2 to 4 years old with glucocorticoid deficiency and mild mineralocorticoid deficiency, even develop naturally masculinized external genitalia at birth when they have 46,XY karyotype. We described thirty patients from unrelated Chinese families, including three non-classic LCAH ones. Four novel mutations were reported, including c.556A > G, c.179-15G > T, c.695delG and c.306 + 3_c.306 + 6delAAGT. The c.772C > T is the most common STAR mutation in Chinese population, suggesting a possibility of founder effect. Enzymatic activity assay combined with clinical characteristics showed a good genotype-phenotype correlation in this study. Residual STAR activity more than 20 % may be correlated with non-classic LCAH phenotype. We support the perspective that onset age may be affected by multiple factors and masculinization should be the main weighting factor for diagnosis of non-classic LCAH. Compared with 46,XX LCAH patients, less 46,XY ones were found in our report. A less comprehensive inspection and an easy diagnosis due to classical phenotype both would reduce the possibility of 46,XY LCAH patients to be referred to specialists or geneticists.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105788DOI Listing
February 2021

Dynamics of soil NO emissions and functional gene abundance in response to biochar application in the presence of earthworms.

Environ Pollut 2021 Jan 29;268(Pt A):115670. Epub 2020 Sep 29.

College of Resources and Environment, Huazhong Agricultural University, Wuhan, 430070, China. Electronic address:

Nitrous oxide (NO) is a devastating greenhouse gas and acts as an ozone-depleting agent. Earthworms are a potential source of soil NO emissions. Application of biochar can mitigate earthworm-induced NO emissions. However, the underlying interactive mechanism between earthworms and biochar in soil NO emissions is still unclear. A 35-day laboratory experiment was conducted to examine the soil NO emission dynamics for four different treatments, earthworm presence with biochar application (EC), earthworm presence without biochar application (E), earthworm absence with biochar application (C) and earthworm absence without biochar application, and the control. Results indicated a negative impact of biochar on earthworm activity, displaying a significantly (p ≤ 0.05) lower survival rate and biomass of earthworms in treatment EC than E. Compared with the control, earthworm presence significantly (p ≤ 0.05) increased cumulative NO emissions, while application of biochar in the presence of earthworms significantly (p ≤ 0.05) decreased cumulative NO emissions (485 and 690 μg kg for treatments EC and E, respectively). Treatments E and EC significantly (p ≤ 0.05) increased soil microbial biomass carbon (MBC), ammonium (NH-N), nitrate (NON), and dissolved organic carbon (DOC) content and soil pH as compared with the control. The gene copy number of 16 S rRNA, AOA, AOB, nirS, and nosZ increased for all treatments when compared with the control; however, a significant (p ≤ 0.05) difference among the studied genes was only observed for the nosZ gene (2.05 and 2.56 × 10 gene copies g soil for treatments E and EC, respectively). Earthworm-induced soil NO emissions were significantly (p ≤ 0.05) reduced by biochar addition. The possible underlying mechanisms may include: (1) short-term negative impacts on earthworm activity; (2) a change of functional gene abundance in earthworm casts; and (3) an increase in soil pH due to addition of biochar.
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http://dx.doi.org/10.1016/j.envpol.2020.115670DOI Listing
January 2021

BAP1 regulates AMPK-mTOR signalling pathway through deubiquitinating and stabilizing tumour-suppressor LKB1.

Biochem Biophys Res Commun 2020 09 30;529(4):1025-1032. Epub 2020 Jul 30.

Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. Electronic address:

Liver kinase B1 (LKB1), a tumour suppressor, participates in many cellular processes, including cell survival, growth, apoptosis, transformation, and metabolism. Upon performing yeast two-hybrid screening, co-immunoprecipitation, and GST pull-down, we identified that BRCA1-associated protein 1 (BAP1), a deubiquitinase, interacts with LKB1. Immunoblotting was performed to examine the effect of BAP1 on the activation of 5' AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), downstream of LKB1. The relationship between BAP1 deficiency and cancer cell proliferation was examined using cell survival assay and soft agar assay. qRT-PCR and oil red O staining were performed to evaluate lipid synthesis. Our findings reveal that BAP1 deubiquitinates LKB1, inhibits its degradation, and stabilises it, thereby affecting AMPK activation and downstream mTOR activity. BAP1 deficiency may enhance cellular proliferation as well as lipid synthesis.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.223DOI Listing
September 2020

Nitrous oxide emissions in response to straw incorporation is regulated by historical fertilization.

Environ Pollut 2020 Nov 13;266(Pt 3):115292. Epub 2020 Aug 13.

Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100081, China.

The incorporation of crop straw with fertilization is beneficial for soil carbon sequestration and cropland fertility improvement. Yet, relatively little is known about how fertilization regulates the emissions of the greenhouse gas nitrous oxide (NO) in response to straw incorporation, particularly in soils subjected to long-term fertilization regimes. Herein, the arable soil subjected to a 31-year history of five inorganic or organic fertilizer regimes (unfertilized; chemical fertilizer application, NPK; 200% NPK application, 2 × NPK; manure application, M; NPK plus manure application, NPKM) was incubated with and without rice straw to evaluate how historical fertilization influences the impact of straw addition on NO emissions. The results showed that compared to the unfertilized treatment, historical fertilization strongly increased NO emissions by 0.48- to 34-fold, resulting from increased contents of hot water-extracted organic carbon (HWEOC), NO, and available phosphorus (Olsen-P). Straw addition had little impact on NO emission from the unfertilized and NPK treatments, primarily due to Olsen-P limitation. In contrast, straw addition increased NO emissions by 102-316% from the 2 × NPK, M, and NPKM treatments as compared to the corresponding straw-unamended treatments. These results indicated that NO emissions in response to straw addition were largely regulated by historical fertilization. The NO emissions were closely associated with the depletion of NO and decoupled from change in NH content, suggesting that NO was the main substrate for NO production upon straw addition. The stoichiometric ratios of HWEOC to mineral N and mineral N to Olsen-P were key factors affecting NO emissions, underscoring the importance of resource stoichiometry in regulating NO emissions. In conclusion, historical fertilization largely regulated the impacts of crop straw incorporation on NO emissions via shifts in NO depletion and the stoichiometry of HWEOC, mineral N, and Olsen-P.
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http://dx.doi.org/10.1016/j.envpol.2020.115292DOI Listing
November 2020

Nitrogen fertilizer application in the rice-growing season can stimulate methane emissions during the subsequent flooded fallow period.

Sci Total Environ 2020 Nov 30;744:140632. Epub 2020 Jun 30.

Key Laboratory of Arable Land Conservation (Middle and Lower Reaches of the Yangtze River), Ministry of Agriculture, College of Resource and Environment, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Winter-flooded rice paddy field (FR), characterized by water conserved in the field during the fallow period, is a typical cropping system in southwest China, leading to considerable methane (CH) emissions. The effect of nitrogen (N) fertilization on CH emissions during rice-growing seasons is well studied in FR, further studies covering N fertilizer applied in the rice-growing seasons affects CH emissions during the subsequent fallow period is needed. Therefore, a field experiment was conducted in an FR of Sichuan province, China, with conventional N fertilized (CN) and N unfertilized (NN) treatments. The cumulative CH emission from CN treatment during the rice-growing season and the subsequent fallow period was 389 ± 29.4 and 158 ± 31.2 kg C ha, which were increased by 29.5% and 395% in comparison with the NN treatment, indicting N applied during the rice growing-season significantly facilitated CH emission during the subsequent fallow period. During the rice-growing season, higher CH emission from CN treatment could be attributed to elevated soil dissolved organic carbon (DOC) content that might have provided sufficient substrates for CH production. During the fallow period, as compared to NN treatment, higher CH emissions from CN treatment could be explained by greater linear regression slopes between CH fluxes, soil temperature and DOC to dissolved inorganic N (DIN) (DOC/DIN) ratio. Moreover, the structural equation model (SEM) described that the soil temperature exhibited the most significant effects on CH emissions for both treatments during the rice-growing season and subsequent fallow period. These findings are a major step forward to showing that N fertilizer applied in the rice-growing season could also affect CH emission during the subsequent fallow period, accompanying other soil parameters controlling CH emission.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140632DOI Listing
November 2020

Urban Atmospheric Environment Quality Assessment by Naturally Growing Bryophytes in Central China.

Int J Environ Res Public Health 2020 06 24;17(12). Epub 2020 Jun 24.

Key Laboratory of Arable Land Conservation (Middle and Lower Reaches of Yangtze River), Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070, China.

Bryophytes are popular biomonitoring plants for atmospheric environments. The objectives of this study were to examine the characteristics of bryophyte communities, determine a suitable monitor species, and assess urban atmospheric environment quality by the joint use of bryophyte features and chemical properties in a large city in China. A pleurocarpous feather moss was recognized as a good biomonitor of atmospheric deposition in central China by investigating bryophyte communities and habitat environment in various ecological function regions of the urban areas in Wuhan. The concentrations of trace elements, including As, Cd, Co, Cr, Cu, Mn, Ni, V, Pb, and Zn, in moss and soil samples from 25 sampling sites were analyzed by inductively coupled plasma mass spectrometry. The concentrations of Cd and Zn in collected from the entire study area were much higher than those in substrate soil. Cd was at the highest ecological risk level among the 10 elements, which contributed 34.5% to the potential ecological risk index (RI). An RI value of 392.8 indicated that urban atmospheric quality in Wuhan was in a considerable potential ecological risk. The index of atmospheric purity, regarding species richness, cover, and frequency of bryophytes, was spatially and negatively correlated with RI, also demonstrated the atmospheric quality. Effective measures should be considered to alleviate certain airborne trace element contamination and protect the environment and human health in this metropolis.
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http://dx.doi.org/10.3390/ijerph17124537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344691PMC
June 2020

The KBTBD6/7-DRD2 axis regulates pituitary adenoma sensitivity to dopamine agonist treatment.

Acta Neuropathol 2020 09 22;140(3):377-396. Epub 2020 Jun 22.

Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Pituitary adenoma (PA) is one of the most common intracranial tumors, and approximately 40% of all PAs are prolactinomas. Dopamine agonists (DAs), such as cabergoline (CAB), have been successfully used in the treatment of prolactinomas. The expression of dopamine type 2 receptor (DRD2) determines the therapeutic effect of DAs, but the molecular mechanisms of DRD2 regulation are not fully understood. In this study, we first demonstrated that DRD2 underwent proteasome-mediated degradation. We further employed the yeast two-hybrid system and identified kelch repeat and BTB (POZ) domain containing 7 (KBTBD7), a substrate adaptor for the CUL3-RING ubiquitin (Ub) ligase complex, as a DRD2-interacting protein. KBTBD6/7 directly interacted with, and ubiquitinated DRD2 at five ubiquitination sites (K221, K226, K241, K251, and K258). CAB, a high-affinity DRD2 agonist, induced DRD2 internalization, and cytoplasmic DRD2 was degraded via ubiquitination under the control of KBTBD6/7, the activity of which attenuated CAB-mediated inhibition of the AKT/mTOR pathway. KBTBD7 knockout (KO) mice were generated using the CRISPR-Cas9 technique, in which the static level of DRD2 protein was elevated in the pituitary gland, thalamus, and heart, compared to that of WT mice. Consistently, the expression of KBTBD6/7 was negatively correlated with that of DRD2 in human pituitary tumors. Moreover, KBTBD7 was highly expressed in dopamine-resistant prolactinomas, but at low levels in dopamine-sensitive prolactinomas. Knockdown of KBTBD6/7 sensitized MMQ cells and primary pituitary tumor cells to CAB treatment. Conversely, KBTBD7 overexpression increased CAB resistance of estrogen-induced in situ rat prolactinoma model. Together, our findings have uncovered the novel mechanism of DRD2 protein degradation and shown that the KBTBD6/7-DRD2 axis regulates PA sensitivity to DA treatment. KBTBD6/7 may thus become a promising therapeutic target for pituitary tumors.
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http://dx.doi.org/10.1007/s00401-020-02180-4DOI Listing
September 2020

Potential of rice straw biochar, sulfur and ryegrass ( L.) in remediating soil contaminated with nickel through irrigation with untreated wastewater.

PeerJ 2020 12;8:e9267. Epub 2020 Jun 12.

Lab of Agricultural Wastes Resource Utilization, College of Resources and Environment, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China.

Background: Untreated wastewater carries substantial amount of heavy metals and causes potential ecological risks to the environment, food quality, soil health and sustainable agriculture.

Methodology: In order to reduce the incidence of nickel (Ni) contamination in soils, two separate experiments (incubation and greenhouse) were conducted to investigate the potentials of rice straw biochar and elemental sulfur in remediating Ni polluted soil due to the irrigation with wastewater. Five incubation periods (1, 7, 14, 28 and 56 days), three biochar doses (0, 10 and 20 g kg of soil) and two doses of sulfur (0 and 5 g kg of soil) were used in the incubation experiment then the Ni was extracted from the soil and analyzed, while ryegrass seeds L. (Poales: Poaceae) and the same doses of biochar and sulfur were used in the greenhouse experiment then the plants Ni-uptake was determined.

Results: The results of the incubation experiment revealed a dose-dependent reduction of DTPA-extractable Ni in soils treated with biochar. Increasing the biochar dose from 0 g kg (control) to 10 or 20 g kg (treatments) decreased the DTPA-extractable Ni from the soil by 24.6% and 39.4%, respectively. The application of sulfur increased the Ni-uptake by ryegrass plant which was used as hyper-accumulator of heavy metals in the green house experiment. However, the biochar decreased the Ni-uptake by the plant therefore it can be used as animal feed.

Conclusions: These results indicate that the biochar and sulfur could be applied separately to remediate the Ni-contaminated soils either through adsorbing the Ni by biochar or increasing the Ni availability by sulfur to be easily uptaken by the hyper-accumulator plant, and hence promote a sustainable agriculture.
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http://dx.doi.org/10.7717/peerj.9267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295020PMC
June 2020

Ubiquitination of IGF2BP3 by E3 ligase MKRN2 regulates the proliferation and migration of human neuroblastoma SHSY5Y cells.

Biochem Biophys Res Commun 2020 08 5;529(1):43-50. Epub 2020 Jun 5.

Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. Electronic address:

Neuroblastoma (NB) is a paediatric tumour that shows great biomolecule and clinical heterogeneity, and patients with NB often develop various neurological complications. Currently, the disease is mainly treated by surgery and still lacks specific therapeutic drugs; therefore, targets are urgently needed. Makorin ring finger protein 2 (MKRN2) is an E3 ligase whose effects on neuroblastoma have not been illustrated. shRNAs for MKRN2 have been designed, and MKRN2-knockdown human neuroblastoma SHSY5Y cells were established. MKRN2 knockdown promotes the proliferation and migration of SHSY5Y cells. Because MKRN2 is an E3 ligase, we performed a series of experiments, and Insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) was identified as a new substrate for MKRN2. IGF2BP3 is an RNA-binding protein that regulates the stability of many mRNAs, including CD44 and PDPN, and our study demonstrated that MKRN2 regulates the expression of CD44 and PDPN in an IGF2BP3-dependent manner. These results suggest that MKRN2 might be a potential therapeutic target for neuroblastoma.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.112DOI Listing
August 2020

An Integrative Synthetic Biology Approach to Interrogating Cellular Ubiquitin and Ufm Signaling.

Int J Mol Sci 2020 Jun 14;21(12). Epub 2020 Jun 14.

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.

Global identification of substrates for PTMs (post-translational modifications) represents a critical but yet dauntingly challenging task in understanding biology and disease pathology. Here we presented a synthetic biology approach, namely 'YESS', which coupled Y2H (yeast two hybrid) interactome screening with PTMs reactions reconstituted in bacteria for substrates identification and validation, followed by the functional validation in mammalian cells. Specifically, the sequence-independent Gateway cloning technique was adopted to afford simultaneous transfer of multiple hit ORFs (open reading frames) between the YESS sub-systems. In proof-of-evidence applications of YESS, novel substrates were identified for UBE3A and UFL1, the E3 ligases for ubiquitination and ufmylation, respectively. Therefore, the YESS approach could serve as a potentially powerful tool to study cellular signaling mediated by different PTMs.
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http://dx.doi.org/10.3390/ijms21124231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352202PMC
June 2020

The influence of soil temperature, methanogens and methanotrophs on methane emissions from cold waterlogged paddy fields.

J Environ Manage 2020 Jun 24;264:110421. Epub 2020 Mar 24.

College of Resources and Environment, Huazhong Agricultural University, Wuhan, 430070, PR China. Electronic address:

Paddy fields are major sources of atmospheric methane (CH). However, CH emissions from cold-waterlogged paddy fields, a major type of paddy soil in China, remain unclear. Here we investigated the CH emissions and associated influential factors in cold-waterlogged paddy fields at two sites (Yangxin County and Daye City) in Hubei Province, South China. Normal paddy fields matched with parental material and cropping system were used as the controls. The CH emissions from cold-waterlogged fields were significantly higher than those from normal fields with (3.0-4.4-fold) or without (3.5-8.6-fold) rice. Rice planting increased CH emissions by 59-78% in cold-waterlogged fields and by 85-247% in normal fields. CH instantaneous fluxes were positively correlated with soil temperature and methanogen mcrA (methyl coenzyme M reductase alpha subunit) and methanotroph pmoA (methane monooxygenase) copy numbers at the annual scale. Under rice planting, mcrA copy number was higher in cold-waterlogged fields than in normal fields at both sites, whereas pmoA copy number had the same trend at the Daye site only. Soil temperature and water content influenced mcrA and pmoA copy numbers in the normal paddy fields, whereas soil organic matter content was more influential in the cold-waterlogged paddy fields. These findings suggest that perennial waterlogging is a prerequisite for substantial CH emissions from cold-waterlogged paddy fields, and it promotes the proliferation of methanogens and methanotrophs under rice planting. Therefore, CH production-oxidation processes are more active in cold-waterlogged paddy fields than in normal paddy fields.
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http://dx.doi.org/10.1016/j.jenvman.2020.110421DOI Listing
June 2020

Enterohemorrhagic E. coli effector NleL disrupts host NF-κB signaling by targeting multiple host proteins.

J Mol Cell Biol 2020 05;12(4):318-321

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

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http://dx.doi.org/10.1093/jmcb/mjaa003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232126PMC
May 2020

Reducing greenhouse gas emissions and enhancing carbon and nitrogen conversion in food wastes by the black soldier fly.

J Environ Manage 2020 Apr 17;260:110066. Epub 2020 Jan 17.

College of Engineering, Huazhong Agricultural University, Wuhan, PR China. Electronic address:

Currently, sustainable utilisation, including recycling and valorisation, is becoming increasingly relevant in environmental management. The wastes bioconversion by the black soldier fly larva (BSFL) has two potential advantages: the larvae can convert the carbon and nitrogen in the biomass waste, and improve the properties of the substrate to reduce the loss of gaseous carbon and nitrogen. In the present study, the conversion rate of carbon, nitrogen and the emissions of greenhouse gases and NH during BSFL bio-treatment of food waste were investigated under different pH conditions. The results showed that the pH of the raw materials is a pivotal parameter affecting the process. The average wet weight of harvested BSFL was 13.26-95.28 mg/larva, with about 1.95-13.41% and 5.40-18.93% of recycled carbon and nitrogen from substrate at a pH from 3.0 to 11.0, respectively. Furthermore, pH is adversely correlated with CO emissions, but positively with NH emissions. Cumulative CO, NH, CH and NO emissions at pH ranging from 3.0 to 11.0 were 88.15-161.11 g kg, 0.15-1.68 g kg, 0.19-2.62 mg kg and 0.02-1.65 mg kg, respectively. Compared with the values in open composting, BSFL bio-treatment of food waste could lead greenhouse gas (especially CH and NO) and NH emissions to decrease. Therefore, a higher pH value of the substrate can increase the larval output and help the mitigation of greenhouse gas emissions.
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http://dx.doi.org/10.1016/j.jenvman.2020.110066DOI Listing
April 2020

Long Non-coding RNA NEAT1 Alleviates Acute-on-Chronic Liver Failure Through Blocking TRAF6 Mediated Inflammatory Response.

Front Physiol 2019 12;10:1503. Epub 2019 Dec 12.

Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Long non-coding RNAs (lncRNAs) have recently been tightly linked to plenty of human diseases. However, knowledge of acute-on-chronic liver failure (ACLF) related lncRNAs remains insufficient. In this work, we studied the role of the lncRNA nuclear enriched abundant transcript 1 (NEAT1) in the pathogenesis of ACLF.

Methods: ACLF model was established by challenging D-galactosamine (D-GalN)/ lipopolysaccharide (LPS) i.p. in rats with cirrhosis. The serum levels of IL-1, IL-6, and HMGB1 were determined using ELISA. Quantitative real time-PCR and western blot were performed to evaluate RNA and protein levels of inflammatory response. RNA immunoprecipitation assay was performed to confirm protein that interacts with NEAT1.

Findings: Over-expression of NEAT1 could interact with TRAF6 and decrease its ubiquitination level, and significantly reduced the expression levels of IL-6, IL-22. Importantly, in ACLF rat model, NEAT1 over-expression reduced several cytokines expression and alleviated the pathological status in contrast to the control group. Additionally, NEAT1 was increased and positively correlated with IL-22 and IL-6 levels in PBMCs from the ACLF patients.

Interpretation: NEAT1 can suppress inflammatory response through blockade of TRAF6 ubiquitination in ACLF rat model, suggesting that lncRNA NEAT1 might play protective roles in the pathogenesis of ACLF and provide promising novel target for pharmacological intervention.
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http://dx.doi.org/10.3389/fphys.2019.01503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920254PMC
December 2019

Effects of mild alternate wetting and drying irrigation and mid-season drainage on CH and NO emissions in rice cultivation.

Sci Total Environ 2020 Jan 2;698:134212. Epub 2019 Sep 2.

Key Laboratory of Arable Land Conservation (Middle and Lower Reaches of Yangtze River) of the Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Rice, one of the major sources of CH and NO emissions, is also the largest consumer of water resources. Mild alternate wetting and drying (AWD) irrigation is widely adopted to save irrigation water resources and maintain rice production, but its effects on CH and NO emissions are unclear. In addition, previous studies have revealed different effects of mid-season drainage on global warming potential (GWP), owing to the different criteria used. In this study, a pot experiment was conducted to investigate the effects of mild AWD irrigation and mid-season drainage (a specific soil moisture) on CH and NO emissions during rice cultivation. Four water management systems were applied: AWD + D0 (mild AWD irrigation without mid-season drainage), AWD + D1 (mild AWD irrigation with mid-season drainage), CF + D0 (continuous flooding without mid-season drainage) and CF + D1 (continuous flooding with mid-season drainage); nitrogen was applied at two levels (N90 and N180) along with each treatment. The results showed that mild AWD irrigation reduced CH cumulative emissions by an average of 87.1% but increased NO cumulative emissions by an average of 280% compared to the values observed with CF irrigation. Mid-season drainage did not affect NO emissions but interrupted CH fluxes and significantly reduced CH cumulative emissions. CH and NO cumulative emissions were reduced by an average of 25.0% and 54.2%, respectively, with N90 application compared to values observed with N180 application. Unexpectedly, mild AWD irrigation did not reduce GWP and yield-scaled GWP unlike CF irrigation because a high NO emission peak occurred during mild AWD irrigation. Furthermore, we observed an obvious trade-off between CH and NO. We suggest that maintaining flooding during nitrogen application but applying mild AWD irrigation for the remaining period may be helpful in reducing CH and NO emissions and GWP.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134212DOI Listing
January 2020

Mitigation of NO emissions from urine treated acidic soils by liming.

Environ Pollut 2019 Dec 13;255(Pt 1):113237. Epub 2019 Sep 13.

College of Resources and Environment, Huazhong Agricultural University, Wuhan, China.

Nitrous oxide (NO) is a devastating greenhouse gas mainly released from soils to the atmosphere. Pasture soils, particularly acidic in nature, are large contributors of atmospheric NO through deposition of urine-N. Devising strategies for reducing NO emissions in acidic soils are the utmost need of the time. Therefore, the present study was carried out to investigate the possible efficacy of dolomite application to reduce NO emissions from urine treated acidic soil. Application of urine to soil enlarged the production of NH-N, NO-N, microbial biomass C (MBC) and dissolved organic C (DOC), resulting in higher NO emissions as compared to the control (soil only). The highest NO emission rate (1.35 μg NO-N kg h) and cumulative flux (408 μg NO-N kg) occurred in urine only treated soil. Dolomite addition, especially higher application dose, greatly reduced NO emissions through improved soil pH. The results suggest that increasing pH of acidic soils is a good applicable approach for reducing NO emissions from urine-treated soils.
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http://dx.doi.org/10.1016/j.envpol.2019.113237DOI Listing
December 2019

Restoring effect of soil acidity and Cu on NO emissions from an acidic soil.

J Environ Manage 2019 Nov 13;250:109535. Epub 2019 Sep 13.

College of Resources and Environment, Huazhong Agricultural University, Wuhan, 430070, China. Electronic address:

Heavy metals are believed to impact soil processes by influencing microbial communities, nutrient cycling or exchanging for essential plant nutrients. Soil pH adjustment highly influences the bio-availability of nutrients and microbial processes. We examined the effect of soil pH manipulation and copper (Cu as CuCl.2HO) application on nitrogen (N) cycling and nitrous oxide (NO) emissions from an acid soil. Increasing amounts of Cu (0, 250, 500 and 1000 mg kg) were added to an acidic soil (pH = 5.44) that was further amended with increasing amounts of dolomite [CaMg(CO)] to increase soil pH. Dolomite increased soil pH values, which reached a maximum without Cu application (-Cu) at day 42 of the experiment. The soil pH values decreased with increasing dose of Cu, and remained low as compared with both control and dolomite amended soil. Ammonium (NH-N) concentrations were higher in Cu contaminated soil as compared with the control and dolomite treated soil. Nitrate (NO-N) concentrations increased in dolomite treated soil when compared with the +Cu alone treatments and control. Microbial biomass carbon (MBC) and nitrogen (MBN) contents were higher in dolomite treated soil as compared with the +Cu treatments and control. The application of increasing amounts of Cu progressively decreased soil MBC and MBN. Nitrous oxide emissions were higher (p ≤ 0.01) in +Cu soil as compared with the control, and increased with increasing Cu concentration in soil. Application of dolomite highly suppressed soil NO emissions in both +Cu and -Cu soils. The results indicate that the effects of heavy metal contamination (specifically Cu contamination) can increase NO emissions, but this can be effectively mitigated through increasing soil pH, also decreasing potential toxic effects on soil microorganisms.
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http://dx.doi.org/10.1016/j.jenvman.2019.109535DOI Listing
November 2019

Effect of moisture content on greenhouse gas and NH emissions from pig manure converted by black soldier fly.

Sci Total Environ 2019 Dec 8;697:133840. Epub 2019 Aug 8.

State Key Laboratory of Agricultural Microbiology, College of Science, Huazhong Agricultural University, Wuhan, China. Electronic address:

The effects of different moisture contents on greenhouse gas (GHG) emissions from pig manure (PM) digested by black soldier fly larvae (BSFL) as well as the accompanying changes of nitrogen and carbon contents in gaseous emissions and residues were studied. A mixture of PM and corncob at the ratio of 2.2:1 was prepared with a moisture content of 45%. Then, distilled water was added to adjust the moisture contents of the mixture to 55%, 65%, 75% and 85%, respectively. The prepared mixtures were digested by BSFL for eight days. The results indicated that BSFL could reduce CH, NO and NH emissions respectively by 72.63-99.99%, 99.68%-99.91% and 82.30-89.92%, compared with conventional composting, while CO emissions increased potentially due to BSFL metabolism. With increasing moisture content, the cumulative CH emissions increased, while cumulative NH emissions peaked at 55% moisture content and then decreased. Interestingly, the tendency of total cumulative CO emissions was consistent with that of the total weight of BSFL. The total GHG emissions were about only 1% those from of traditional composting at the optimum moisture content (75%), which was the most favorable for the growth of BSFL. The nitrogen and carbon contents of BSFL content in all treatments accounted for 1.03%-12.67% and 0.25%-4.68% of the initial contents in the raw materials, respectively. Moreover, the residues retained 71.12%-90.58% carbon and 67.91%-80.39% nitrogen of the initial raw materials. Overall, our results suggest that BSFL treatment is an environment-friendly alternative for decreasing CH, NO and NH emissions as well as reducing global warming potential (GWP).
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http://dx.doi.org/10.1016/j.scitotenv.2019.133840DOI Listing
December 2019

ER-localized Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection.

Nat Microbiol 2019 12;4(12):2331-2346

State Key Laboratory of Cell Biology, Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Innovation Center for Cell Signaling Network, Shanghai, China.

The special organelle-located MAVS, STING and TLR3 are important for clearing viral infections. Although TLR4 triggers NF-κB activation to produce pro-inflammatory cytokines for bacterial clearance, effectors with special organelle localization have not been identified. Here, we screened more than 280 E3 ubiquitin ligases and discovered that the endoplasmic reticulum-located Hrd1 regulates TLR4-induced inflammation during bacterial infection. Hrd1 interacts directly with the deubiquitinating enzyme Usp15. Unlike the classical function of Hrd1 in endoplasmic reticulum-associated degradation, Usp15 is not degraded but loses its deubiquitinating activity for IκBα deubiquitination, resulting in excessive NF-κB activation. Importantly, Hrd1 deficiency in macrophages protects mice against lipopolysaccharide-induced septic shock, and knockdown of Usp15 in Hrd1-knockout macrophages restores the reduced IL-6 production. This study proposes that there is crosstalk between Hrd1 and TLR4, thereby linking the endoplasmic reticulum-plasma membrane function during bacterial infection.
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http://dx.doi.org/10.1038/s41564-019-0542-2DOI Listing
December 2019

Maternal exposure to triclosan constitutes a yet unrecognized risk factor for autism spectrum disorders.

Cell Res 2019 Oct 28;29(10):866-869. Epub 2019 Aug 28.

University of Chinese Academy of Sciences; State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China.

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http://dx.doi.org/10.1038/s41422-019-0220-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796921PMC
October 2019