Publications by authors named "Fang Xiong"

117 Publications

AFAP1-AS1: a rising star among oncogenic long non-coding RNAs.

Sci China Life Sci 2021 May 13. Epub 2021 May 13.

NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China, Cancer Research Institute, Central South University, Changsha, 410078, China.

Long non-coding RNAs (lncRNAs) have become a hotspot in biomedical research. This interest reflects their extensive involvement in the regulation of the expression of other genes, and their influence on the occurrence and development of a variety of human diseases. Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1) is a recently discovered oncogenic lncRNA. It is highly expressed in a variety of solid tumors, and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs, or by the direct binding to other proteins. Ultimately, AFAP1-AS1 promotes proliferation, chemotherapy resistance, and resistance to apoptosis, maintains stemness, and enhances invasion and migration of tumor cells. This paper summarizes the research concerning AFAP1-AS1 in malignant tumors, including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors. We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research. AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules.
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http://dx.doi.org/10.1007/s11427-020-1874-6DOI Listing
May 2021

Serum microRNAs predict response of patients with chronic hepatitis B to antiviral therapy.

Int J Infect Dis 2021 May 14;108:37-44. Epub 2021 May 14.

Hepatology and Cancer Biotherapy Ward/Department of Medical Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address:

Objectives: To investigate the feasibility of using serum microRNAs to predict the response of chronic hepatitis B (CHB) patients to antiviral therapy over 48 weeks.

Methods: Sixty-five CHB patients were divided into responder and non-responder groups according to whether hepatitis B e antigen seroconversion occurred at week 48. Serum microRNAs were dynamically detected.

Results: At baseline, the responder group had lower miR-122-5p (P = 0.006) and higher miR-1307-3p (P = 0.018) than the non-responder group. After therapy, miR-320a-3p and miR-320c were higher in the responder group than the non-responder group (P = 0.043 and 0.031, respectively). In the responder group, 9 microRNAs-let-7d-5p, let-7f-5p, let-7i-5p, miR-126-3p, miR-1307-3p, miR-181a-5p, miR-21-5p, miR-425-5p and miR-652-3p-were significantly lower at week 48 than at baseline (P < 0.05); however, miR-320a-3p was significantly elevated after therapy (P < 0.001). In the non-responder group, miR-122-5p significantly decreased after therapy compared with baseline (P = 0.005). Finally, miR-122-5p was positively correlated with titer of hepatitis B virus DNA (r = 0.438, P = 0.008) and hepatitis B e antigen (r = 0.610, P < 0.001), and miR-320a-3p was negatively correlated with hepatitis B virus DNA titer (r = -0.366, P = 0.028) at baseline.

Conclusions: The dynamic fluctuations of serum microRNAs might predict the efficacy of antiviral therapy for CHB.
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http://dx.doi.org/10.1016/j.ijid.2021.05.015DOI Listing
May 2021

What are the applications of single-cell RNA sequencing in cancer research: a systematic review.

J Exp Clin Cancer Res 2021 May 11;40(1):163. Epub 2021 May 11.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Single-cell RNA sequencing (scRNA-seq) is a tool for studying gene expression at the single-cell level that has been widely used due to its unprecedented high resolution. In the present review, we outline the preparation process and sequencing platforms for the scRNA-seq analysis of solid tumor specimens and discuss the main steps and methods used during data analysis, including quality control, batch-effect correction, normalization, cell cycle phase assignment, clustering, cell trajectory and pseudo-time reconstruction, differential expression analysis and gene set enrichment analysis, as well as gene regulatory network inference. Traditional bulk RNA sequencing does not address the heterogeneity within and between tumors, and since the development of the first scRNA-seq technique, this approach has been widely used in cancer research to better understand cancer cell biology and pathogenetic mechanisms. ScRNA-seq has been of great significance for the development of targeted therapy and immunotherapy. In the second part of this review, we focus on the application of scRNA-seq in solid tumors, and summarize the findings and achievements in tumor research afforded by its use. ScRNA-seq holds promise for improving our understanding of the molecular characteristics of cancer, and potentially contributing to improved diagnosis, prognosis, and therapeutics.
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http://dx.doi.org/10.1186/s13046-021-01955-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111731PMC
May 2021

The long noncoding RNA AATBC promotes breast cancer migration and invasion by interacting with YBX1 and activating the YAP1/Hippo signaling pathway.

Cancer Lett 2021 Aug 2;512:60-72. Epub 2021 May 2.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

Long noncoding RNAs (lncRNAs) play an important role in the regulation of gene expression and are involved in several pathological responses. However, many important lncRNAs in breast cancer have not been identified and their expression levels and functions in breast cancer remain unknown. In this study, the lncRNA apoptosis-associated transcript in bladder cancer (AATBC) was found to be significantly highly expressed in breast cancer patients. In vitro and in vivo experiments indicated that AATBC promoted breast cancer metastasis. Further studies revealed that AATBC activated the YAP1/Hippo signaling pathway through the AATBC-YBX1-MST1 axis. This is also an important supplement to the composition of the YAP1/Hippo signaling pathway. The model of "AATBC-YAP1" may bring a new dawn to the treatment of breast cancer.
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http://dx.doi.org/10.1016/j.canlet.2021.04.025DOI Listing
August 2021

N6-methyladenosine-dependent signalling in cancer progression and insights into cancer therapies.

J Exp Clin Cancer Res 2021 Apr 29;40(1):146. Epub 2021 Apr 29.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

The N6-methyladenosine (m6A) modification is a dynamic and reversible epigenetic modification, which is co-transcriptionally deposited by a methyltransferase complex, removed by a demethylase, and recognized by reader proteins. Mechanistically, m6A modification regulates the expression levels of mRNA and nocoding RNA by modulating the fate of modified RNA molecules, such as RNA splicing, nuclear transport, translation, and stability. Several studies have shown that m6A modification is dysregulated in the progression of multiple diseases, especially human tumors. We emphasized that the dysregulation of m6A modification affects different signal transduction pathways and involves in the biological processes underlying tumor cell proliferation, apoptosis, invasion and migration, and metabolic reprogramming, and discuss the effects on different cancer treatment.
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http://dx.doi.org/10.1186/s13046-021-01952-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082653PMC
April 2021

Single-cell RNA sequencing in cancer research.

J Exp Clin Cancer Res 2021 Mar 1;40(1):81. Epub 2021 Mar 1.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, China.

Single-cell RNA sequencing (scRNA-seq), a technology that analyzes transcriptomes of complex tissues at single-cell levels, can identify differential gene expression and epigenetic factors caused by mutations in unicellular genomes, as well as new cell-specific markers and cell types. scRNA-seq plays an important role in various aspects of tumor research. It reveals the heterogeneity of tumor cells and monitors the progress of tumor development, thereby preventing further cellular deterioration. Furthermore, the transcriptome analysis of immune cells in tumor tissue can be used to classify immune cells, their immune escape mechanisms and drug resistance mechanisms, and to develop effective clinical targeted therapies combined with immunotherapy. Moreover, this method enables the study of intercellular communication and the interaction of tumor cells and non-malignant cells to reveal their role in carcinogenesis. scRNA-seq provides new technical means for further development of tumor research and is expected to make significant breakthroughs in this field. This review focuses on the principles of scRNA-seq, with an emphasis on the application of scRNA-seq in tumor heterogeneity, pathogenesis, and treatment.
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http://dx.doi.org/10.1186/s13046-021-01874-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919320PMC
March 2021

Bortezomib suppresses self-renewal and leukemogenesis of leukemia stem cell by NF-ĸB-dependent inhibition of CDK6 in MLL-rearranged myeloid leukemia.

J Cell Mol Med 2021 Mar 17;25(6):3124-3135. Epub 2021 Feb 17.

Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Acute myeloid leukaemia (AML) with chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukaemia (MLL) is an aggressive subtype with low overall survival. Bortezomib (Bort) is first applied in multiple myeloma. However, whether bort possesses anti-self-renewal and leukemogenesis of leukaemia stem cell (LSC) in AML with MLL rearrangements is still unclear. Here, we found that bort suppressed cell proliferation and decreased colony formation in human and murine leukaemic blasts. Besides, bort reduced the frequency and function of LSC, inhibited the progression, and extended the overall survival in MLL-AF9 (MF9) -transformed leukaemic mice. Furthermore, bort decreased the percentage of human LSC (CD34 CD38 ) cells and extended the overall survival in AML blasts-xenografted NOD/SCID-IL2Rγ (NSG) mice. Mechanistically, cyclin dependent kinase 6 (CDK6) was identified as a bort target by RNA sequencing. Bort reduced the expressions of CDK6 by inhibiting NF ĸB recruitment to the promoter of CDK6, leading to the abolishment of NF ĸB DNA-binding activity for CDK6 promoter. Overexpression of CDK6 partially rescued bort-induced anti-leukemogenesis. Most importantly, bort had little side-effect against the normal haematological stem and progenitor cell (HSPC) and did not affect CDK6 expression in normal HSPC. In conclusion, our results suggest that bort selectively targets LSC in MLL rearrangements. Bort might be a prospective drug for AML patients bearing MLL rearrangements.
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http://dx.doi.org/10.1111/jcmm.16377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957264PMC
March 2021

A novel small molecule CXCR4 antagonist potently mobilizes hematopoietic stem cells in mice and monkeys.

Stem Cell Res Ther 2021 Jan 7;12(1):17. Epub 2021 Jan 7.

School of Life Sciences, Tsinghua University, Beijing, China.

Background: Hematopoietic stem cell (HSC) transplantation is an effective treatment strategy for many types of diseases. Peripheral blood (PB) is the most commonly used source of bone marrow (BM)-derived stem cells for current HSC transplantation. However, PB usually contains very few HSCs under normal conditions, as these cells are normally retained within the BM. This retention depends on the interaction between the CXC chemokine receptor 4 (CXCR4) expressed on the HSCs and its natural chemokine ligand, stromal cell-derived factor (SDF)-1α (also named CXCL12) present in the BM stromal microenvironment. In clinical practice, blocking this interaction with a CXCR4 antagonist can induce the rapid mobilization of HSCs from the BM into the PB.

Methods: C3H/HEJ, DBA/2, CD45.1, and CD45.2 mice and monkeys were employed in colony-forming unit (CFU) assays, flow cytometry assays, and competitive/noncompetitive transplantation assays, to assess the short-term mobilization efficacy of HF51116 and the long-term repopulating (LTR) ability of HSCs. Kinetics of different blood cells and the concentration of HF51116 in PB were also explored by blood routine examinations and pharmacokinetic assays.

Results: In this paper, we report that a novel small molecule CXCR4 antagonist, HF51116, which was designed and synthesized by our laboratory, can rapidly and potently mobilize HSCs from BM to PB in mice and monkeys. HF51116 not only mobilized HSCs when used alone but also synergized with the mobilizing effects of granulocyte colony-stimulating factor (G-CSF) after co-administration. Following mobilization by HF51116 and G-CSF, the long-term repopulating (LTR) and self-renewing HSCs were sufficiently engrafted in primary and secondary lethally irradiated mice and were able to rescue and support long-term mouse survival. In monkeys, HF51116 exhibited strong HSC mobilization activity and quickly reached the highest in vivo blood drug concentration.

Conclusions: These results demonstrate that HF51116 is a new promising stem cell mobilizer which specifically targets CXCR4 and merits further preclinical and clinical studies.
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http://dx.doi.org/10.1186/s13287-020-02073-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791974PMC
January 2021

Clinical threshold of the translucency parameter of maxillary central incisors.

Authors:
Hui Xia Fang Xiong

Dent Mater J 2021 Mar 24;40(2):547-551. Epub 2020 Dec 24.

Department of Prosthodontics, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University.

The aim of this in vivo study is to describe the clinical threshold and relative factors associated with the translucency of maxillary central incisors. Bilateral maxillary central incisors were measured in 106 individuals using a digital colorimeter against black and white backings. The translucency parameters (TP) of incisors and the difference in TP (ΔTP) between the left and right maxillary central incisors of the same individual was calculated. The mean TP value of the maxillary incisors was 8.22. There was a significant effect of age on the translucency of the maxillary central incisors (p<0.05). The TP of females was higher than that of males (p<0.05). The absolute mean value of ΔTP was 1.33. The ΔTP of the two maxillary central incisors in the same individual can be used as a reference for the threshold value of translucency.
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http://dx.doi.org/10.4012/dmj.2020-137DOI Listing
March 2021

Comparison of the clinical manifestations between different age groups of patients with overseas imported COVID-19.

PLoS One 2020 4;15(12):e0243347. Epub 2020 Dec 4.

Department of Respiratory and Critical Care Medicine, Beijing Engineering Research Center of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

The current study investigated the clinical manifestations and outcomes of different age groups of patients with overseas imported COVID-19. In total, 53 COVID-19 patients admitted to the designated Beijing Xiaotangshan Hospital between March 16 and April 15 of 2020 were included. Based on the percentage of disease aggravation during hospital stay according to CT, the patients were divided into two groups: ≤40 years (group A; n = 41) and >40 years (group B; n = 12). The demographic data, epidemiological history, disease courses, potential complications, clinical symptoms, lab indices, chest CT outcomes, treatment protocols and turnovers of the two groups were compared. According to clinical typing, compared with group A, group B had a significantly greater proportion of the common type of COVID-19 (P<0.05) and greater comorbidity of type 2 diabetes (P<0.001). The two groups presented significantly different lab indices. Group B showed significantly more frequent CT abnormalities, with greater proportions of multiple lesions and bilateral lung involvement (P<0.05). During hospitalization, group B had a greater proportion of disease aggravation according to CT (P<0.01). Compared with group A, group B received a significantly greater proportion of antiviral therapy and presented a significantly greater occurrence of adverse drug reactions (P<0.05). The two groups did not significantly differ in time from admission to clinical symptom improvement or from disease onset to negative outcomes according to nucleic acid testing, the appearance of IgG or the appearance of IgM. They also did not significantly differ in length of stay. Older imported COVID-19 patients, particularly those with type 2 diabetes, showed a broader pulmonary extent and faster development of the disease, more severe pathogenetic conditions and a greater risk of developing a critically severe type. Increased attention should be given to this population in clinical practice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243347PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717545PMC
January 2021

Warming leads to more closed nitrogen cycling in nitrogen-rich tropical forests.

Glob Chang Biol 2021 Feb 21;27(3):664-674. Epub 2020 Nov 21.

Key Laboratory of Vegetation Restoration and Management of Degraded Ecosystems, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, China.

Warming may have profound effects on nitrogen (N) cycling by changing plant N demand and underground N supply. However, large uncertainty exists regarding how warming affects the integrated N dynamic in tropical forests. We translocated model plant-soil ecosystems from a high-altitude site (600 m) to low-altitude sites at 300 and 30 m to simulate warming by 1.0°C and 2.1°C, respectively, in tropical China. The effects of experimental warming on N components in plant, soil, leaching, and gas were studied over 6 years. Our results showed that foliar δ N values and inorganic N (NH -N and NO -N) leaching were decreased under warming, with greater decreases under 2.1°C of warming than under 1.0°C of warming. The 2.1°C of warming enhanced plant growth, plant N uptake, N resorption, and fine root biomass, suggesting higher plant N demand. Soil total N concentrations, NO -N concentrations, microbial biomass N and arbuscular mycorrhizal fungal abundance were decreased under 2.1°C of warming, which probably restricted bioavailable N supply and arbuscular mycorrhizal contribution of N supply to plants. These changes in plants, soils and leaching indicated more closed N cycling under warming, the magnitude of which varied over time. The closed N cycling became pronounced during the first 3 years of warming where the sustained reductions in soil inorganic N could not meet plant N demand. Subsequently, the closed N cycling gradually mitigated, as observed by attenuated positive responses of plant growth and less negative responses of microbial biomass N to warming during the last 3 years. Overall, the more closed N cycling under warming could facilitate ecosystem N retention and affect production in these tropical forests, but these effects would be eventually mitigated with long-term warming probably due to the restricted plant growth and microbial acclimation.
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http://dx.doi.org/10.1111/gcb.15432DOI Listing
February 2021

circSETD3 regulates MAPRE1 through miR-615-5p and miR-1538 sponges to promote migration and invasion in nasopharyngeal carcinoma.

Oncogene 2021 01 29;40(2):307-321. Epub 2020 Oct 29.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Circular RNAs (circRNAs) play an essential role in tumorigenesis and development. However, they have rarely been investigated in nasopharyngeal carcinoma (NPC). This study aimed to investigate the role of circRNA in the invasion and metastasis of NPC. We screened and verified the high expression of circSETD3 in NPC cell lines using RNA sequencing (RNA-Seq) and verified the results of NPC biopsy samples using real-time quantitative polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). In vivo and in vitro experiments indicated that circSETD3 could promote NPC cell invasion and migration. We compared the proteomic data of NPC cells before and after the overexpression or knockdown of circSETD3 in combination with bioinformatics prediction and experimental verification. It was found that circSETD3 competitively adsorbs to miR-615-5p and miR-1538 and negates their inhibitory effect on MAPRE1 mRNA, thereby upregulating the expression of MAPRE1. The upregulated MAPRE1 then inhibits the acetylation of α-tubulin, promotes the dynamic assembly of microtubules, and enhances the invasion and migration capabilities of NPC cells. The results of this study suggest that circSETD3 is a novel molecular marker and a potential target for NPC diagnosis and treatment.
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http://dx.doi.org/10.1038/s41388-020-01531-5DOI Listing
January 2021

EBV-miR-BART12 accelerates migration and invasion in EBV-associated cancer cells by targeting tubulin polymerization-promoting protein 1.

FASEB J 2020 12 23;34(12):16205-16223. Epub 2020 Oct 23.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Epstein-Barr virus (EBV) infection leads to cancers with an epithelial origin, such as nasopharyngeal cancer and gastric cancer, as well as multiple blood cell-based malignant tumors, such as lymphoma. Interestingly, EBV is also the first virus found to carry genes encoding miRNAs. EBV encodes 25 types of pre-miRNAs which are finally processed into 44 mature miRNAs. Most EBV-encoded miRNAs were found to be involved in the occurrence and development of EBV-related tumors. However, the function of EBV-miR-BART12 remains unclear. The findings of the current study revealed that EBV-miR-BART12 binds to the 3'UTR region of Tubulin Polymerization-Promoting Protein 1 (TPPP1) mRNA and downregulates TPPP1, thereby promoting the invasion and migration of EBV-related cancers, such as nasopharyngeal cancer and gastric cancer. The mechanism underlying this process was found to be the inhibition of TPPP1 by EBV-miRNA-BART12, which, in turn, inhibits the acetylation of α-tubulin, and promotes the dynamic assembly of microtubules, remodels the cytoskeleton, and enhances the acetylation of β-catenin. β-catenin activates epithelial to mesenchymal transition (EMT). These two processes synergistically promote the invasion and metastasis of tumor cells. To the best of our knowledge, this is the first study to reveal the role of EBV-miRNA-BART12 in the development of EBV-related tumors as well as the mechanism underlying this process, and suggests potential targets and strategies for the treatment of EBV-related tumors.
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http://dx.doi.org/10.1096/fj.202001508RDOI Listing
December 2020

Long non-coding RNA expression profiles and related regulatory networks in areca nut chewing-induced tongue squamous cell carcinoma.

Oncol Lett 2020 Dec 29;20(6):302. Epub 2020 Sep 29.

Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.

Areca nut chewing is an important risk factor for developing tongue squamous cell carcinoma (TSCC), although the underlying molecular mechanism is unknown. To determine the potential molecular mechanisms of areca nut chewing-induced TSCC, the present study performed whole-genome detection with five pairs of TSCC and adjacent normal tissues, via mRNA- and long non-coding (lnc)RNA-gene chip analysis. A total of 3,860 differentially expressed genes were identified, including 2,193 lncRNAs and 1,667 mRNAs. Gene set-enrichment analysis revealed that the differentially expressed mRNAs were enriched in chromosome 22q13, 8p21 and 3p21 regions, and were regulated by nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). The results of ingenuity pathway analysis revealed that these mRNAs were significantly enriched for inflammatory immune-related signaling pathways. A co-expression network of mRNAs and lncRNAs was constructed by performing weighted gene co-expression network analysis. The present study focused on NF-κB-, IRF- and Th cell-signaling pathway-related lncRNAs and the corresponding mRNA-lncRNA regulatory networks. To the best of our knowledge, the present study was the first to investigate differential mRNA- and lncRNA-expression profiles in TSCCs induced by areca nut chewing. Inflammation-related mRNA-lncRNA regulatory networks driven by IRFs and NF-κB were identified, as well as the Th cell-related signaling pathways that play important carcinogenic roles in areca nut chewing-induced TSCC. These differentially expressed mRNAs and lncRNAs, and their regulatory networks provide insight for further analysis on the molecular mechanism of areca nut chewing-induced TSCC, candidate molecular markers and targets for further clinical intervention.
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http://dx.doi.org/10.3892/ol.2020.12165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573881PMC
December 2020

The role of microenvironment in tumor angiogenesis.

J Exp Clin Cancer Res 2020 Sep 30;39(1):204. Epub 2020 Sep 30.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Tumor angiogenesis is necessary for the continued survival and development of tumor cells, and plays an important role in their growth, invasion, and metastasis. The tumor microenvironment-composed of tumor cells, surrounding cells, and secreted cytokines-provides a conducive environment for the growth and survival of tumors. Different components of the tumor microenvironment can regulate tumor development. In this review, we have discussed the regulatory role of the microenvironment in tumor angiogenesis. High expression of angiogenic factors and inflammatory cytokines in the tumor microenvironment, as well as hypoxia, are presumed to be the reasons for poor therapeutic efficacy of current anti-angiogenic drugs. A combination of anti-angiogenic drugs and antitumor inflammatory drugs or hypoxia inhibitors might improve the therapeutic outcome.
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http://dx.doi.org/10.1186/s13046-020-01709-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526376PMC
September 2020

Upregulation of long non-coding RNA LOC284454 may serve as a new serum diagnostic biomarker for head and neck cancers.

BMC Cancer 2020 Sep 24;20(1):917. Epub 2020 Sep 24.

Department of Stomatology, NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, No.88 Xiangya Road, Changsha, Hunan, P. R. China, 410078.

Background: Identification of effective diagnostic and prognostic biomarkers of cancer is necessary for improving precision medicine. Long non-coding RNAs (lncRNAs) play an important regulatory role in tumor initiation and progression. The lncRNA LOC284454 is distinctly expressed in various head and neck cancers (HNCs), as demonstrated by our previous bioinformatics analysis. However, the expression levels and functions of LOC284454 in cancer are still unclear.

Methods: We investigated the dysregulation of lncRNAs in HNCs using the GEO database and found that LOC284454 was highly expressed in HNCs. Serum samples from 212 patients with HNCs and 121 normal controls were included in this biomarker study. We measured the expression of LOC284454 in the sera of HNC patients and normal controls using RT-qPCR. Receiver operating characteristics (ROC) analysis is an important statistical method that is widely used in clinical diagnosis and disease screening. ROC was used to analyze the clinical value of LOC284454 in the early diagnosis of HNCs.

Results: LOC284454 was significantly upregulated in the sera of patients with nasopharyngeal carcinoma, oral cancer, and thyroid cancer. LOC284454 upregulation had good clinical diagnostic value in these cancers, as evaluated by area under the ROC curve values of 0.931, 0.698, and 0.834, respectively.

Conclusions: LOC284454 may be a valuable serum biomarker for HNCs facilitating the early diagnosis of malignant cancers. Further studies are needed to elucidate the mechanisms underlying the involvement of LOC284454 in HNCs. This study provides the first evidence that LOC284454 may be a serum biomarker for HNCs.
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http://dx.doi.org/10.1186/s12885-020-07408-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517628PMC
September 2020

Clinical and economic impact of oxidized regenerated cellulose for surgeries in a Chinese tertiary care hospital.

J Comp Eff Res 2020 10 22;9(15):1079-1090. Epub 2020 Sep 22.

Normin Health Consulting Ltd, Toronto L5R 0E9, Canada.

 To assess the impact of oxidized regenerated cellulose (ORC) on blood transfusion and hospital costs associated with surgeries. This retrospective cohort study selected ten surgeries to create propensity-score matching groups to compare ORC versus nonORC (conventional hemostatic techniques such as manual pressure, ligature and electrocautery). NonORC was associated with both higher blood transfusion volume and higher hospital costs than ORC in endoscopic transnasal sphenoidal surgery, nonskull base craniotomy, hepatectomy, cholangiotomy, gastrectomy and lumbar surgery. However, nonORC was associated with better outcomes than ORC in open colorectal surgery, mammectomy and hip arthroplasty surgery. When compared with conventional hemostatic technique, using ORC could impact blood transfusion and hospital costs differently by surgical settings.
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http://dx.doi.org/10.2217/cer-2020-0166DOI Listing
October 2020

CircARHGAP12 promotes nasopharyngeal carcinoma migration and invasion via ezrin-mediated cytoskeletal remodeling.

Cancer Lett 2021 01 12;496:41-56. Epub 2020 Sep 12.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medicine Sciences, Central South University, Changsha, Hunan, PR China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China. Electronic address:

An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in malignant tumor initiation and progression; however, many circRNAs are yet unidentified, and the role of circRNAs in nasopharyngeal carcinoma (NPC) is unclear. Using RNA sequencing, we discovered a novel circRNA, termed circARHGAP12, that was processed from the pre-mRNA of the ARHGAP12 gene. CircARHGAP12 was significantly upregulated in NPC tissues and cell lines and promoted NPC cell migration and invasion. Overexpression or knockdown experiments revealed that circARHGAP12 regulates the expression of cytoskeletal remodeling-related proteins EZR, TPM3, and RhoA. CircARHGAP12 was found to bind directly to the 3' UTR of EZR mRNA and promote its stability; moreover, EZR protein interacted with TPM3 and RhoA and formed a complex to promote NPC cell invasion and metastasis. This study identified the novel circRNA circARHGAP12, characterized its biological function and mechanism, and increased our understanding of circRNAs in NPC pathogenesis. In particular, circARHGAP12 was found to promote the malignant biological phenotype of NPC via cytoskeletal remodeling, thus providing a clue for targeted therapy of NPC.
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http://dx.doi.org/10.1016/j.canlet.2020.09.006DOI Listing
January 2021

Extended duration therapy regimens based on Pegylated interferon for chronic hepatitis B patients focusing on hepatitis B surface antigen loss: A systematic review and meta-analysis.

Infect Genet Evol 2020 11 5;85:104492. Epub 2020 Aug 5.

International Medical Department, Beijing You-an Hospital, Capital Medical University, Beijing, China. Electronic address:

Aims: Hepatitis B surface antigen (HBsAg) loss is associated with disease control and improvement of prognosis. Therefore, it is regarded as the optimal treatment endpoint for chronic hepatitis B (CHB) patients. Pegylated interferon (PegIFN)-based extended therapy regimens was assessed in several studies. In order to summarize a conclusion on the HBsAg loss rate and safety in this regimen, a systematic review and meta-analysis was performed.

Methods: Studies on Hepatitis B and PegIFN were searched thoroughly in Pubmed, EMBASE, and the Cochrane Library from inception to November 18, 2019. The primary endpoint of this study was the HBsAg loss rate at the end of the extended duration therapy. The secondary endpoint was safety. All analyses were performed by using the R3.6.1 version Software. Quality assessment of RCTs was carried out by using Review manager 5.3.

Results: A total of nine studies, including 545 CHB patients met the inclusion criteria. The pooled HBsAg loss rate after PegIFN-based extended duration therapy was 11% (95% CI: 0.05-0.19), I = 82%, P < 0.01(Q test). The extended duration therapy regimen was safe and tolerable. Subgroup analysis showed HBsAg loss rates were 14% (95% CI: 0.04-0.29) and 10% (95% CI: 0.02-0.20) respectively for HBeAg positive and HBeAg negative patients (P = 0.52). HBsAg loss rates were 11%(95%CI:0.03-0.22)and 12%(95%CI:0.04-0.24)respectively for PegIFN monotherapy and PegIFN with Nucleos(t)ide analogs (NAs) therapy (P = 0.84). HBsAg loss rates were 25% (95% CI: 0.19-0.31) and 8% (95% CI: 0.03-0.15) respectively for the advantageous group and non-advantageous group (P = 0.001).

Conclusions: For CHB patients, extended duration of PegIFNα-based treatment for more than 48 weeks is likely to improve HBsAg clearance rate. Specially, the advantageous group will benefit a lot. In addition, the extended duration therapy regimen is safe and tolerable.
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http://dx.doi.org/10.1016/j.meegid.2020.104492DOI Listing
November 2020

Metabolic crosstalk in the tumor microenvironment regulates antitumor immunosuppression and immunotherapy resisitance.

Cell Mol Life Sci 2021 Jan 11;78(1):173-193. Epub 2020 Jul 11.

Department of Stomatology, NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, 410078, China.

The successful treatment of human cancers by immunotherapy has been made possible by breakthroughs in the discovery of immune checkpoint regulators, including CTLA-4 and PD-1/PD-L1. However, the immunosuppressive effect of the tumor microenvironment still represents an important bottleneck that limits the success of immunotherapeutic approaches. The tumor microenvironment influences the metabolic crosstalk between tumor cells and tumor-infiltrating immune cells, creating competition for the utilization of nutrients and promoting immunosuppression. In addition, tumor-derived metabolites regulate the activation and effector function of immune cells through a variety of mechanisms; in turn, the metabolites and other factors secreted by immune cells can also become accomplices to cancer development. Immune-metabolic checkpoint regulation is an emerging concept that is being studied with the aim of restoring the immune response in the tumor microenvironment. In this review, we summarize the metabolic reprogramming of various cell types present in the tumor microenvironment, with a focus on the interaction between the metabolic pathways of these cells and antitumor immunosuppression. We also discuss the main metabolic checkpoints that could provide new means of enhancing antitumor immunotherapy.
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http://dx.doi.org/10.1007/s00018-020-03581-0DOI Listing
January 2021

Design, synthesis, and biological characterization of a new class of symmetrical polyamine-based small molecule CXCR4 antagonists.

Eur J Med Chem 2020 Aug 16;200:112410. Epub 2020 May 16.

Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China. Electronic address:

CXCR4, a well-studied coreceptor of human immunodeficiency virus type 1 (HIV-1) entry, recognizes its cognate ligand SDF-1α (also named CXCL12) which plays many important roles, including regulating immune cells, controlling hematopoietic stem cells, and directing cancer cells migration. These pleiotropic roles make CXCR4 an attractive target to mitigate human disorders. Here a new class of symmetrical polyamines was designed and synthesized as potential small molecule CXCR4 antagonists. Among them, a representative compound 21 (namely HF50731) showed strong CXCR4 binding affinity (mean IC = 19.8 nM) in the CXCR4 competitive binding assay. Furthermore, compound 21 significantly inhibited SDF-1α-induced calcium mobilization and cell migration, and blocked HIV-1 infection via antagonizing CXCR4 coreceptor function. The structure-activity relationship analysis, site-directed mutagenesis, and molecular docking were conducted to further elucidate the binding mode of compound 21, suggesting that compound 21 could primarily occupy the minor subpocket of CXCR4 and partially bind in the major subpocket by interacting with residues W94, D97, D171, and E288. Our studies provide not only new insights for the fragment-based design of small molecule CXCR4 antagonists for clinical applications, but also a new and effective molecular probe for CXCR4-targeting biological studies.
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http://dx.doi.org/10.1016/j.ejmech.2020.112410DOI Listing
August 2020

Clinical characteristics of chronic hepatitis B cured by peginterferon in combination with nucleotide analogs.

Int J Infect Dis 2020 Jul 29;96:562-566. Epub 2020 May 29.

Hepatology and Cancer Biotherapy Ward, Beijing You-An Hospital, Capital Medical University, Beijing, China. Electronic address:

Objectives: The purpose of this study was to analyze the clinical characteristics of chronic hepatitis B (CHB) cured by antiviral therapy.

Methods: Forty-two patients with CHB were enrolled. All patients had been treated with peginterferon (Peg-IFN) in combination with nucleoside analogue (NA) therapy for variable amounts of time, and all had been successfully cured of the disease.

Results: The combined treatment time for all participants was 124.7 ± 58.8 weeks, and the average Peg-IFN treatment time was 102.6 ± 56.1 weeks. At 24 weeks, Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) had decreased more than 50% from baseline. Multivariate logistic regression analysis of the week 96 HBsAg-clearing group and the non-HBsAg-clearing group showed a statistically significant difference in baseline HBV DNA levels and week 48 HBsAg levels. Those which baseline HBV DNA was < 2.75 log IU/mL, and week 48 HBsAg levels were < 0.88 log IU/mL were more likely to achieve rapid HBsAg clearance at 96 weeks. This suggests that low levels of baseline HBV DNA and week 48 HBsAg are a predictor of rapid HBsAg clearance at 96 weeks.

Conclusions: Individualized extension of combination therapy to more than 96 weeks depending on the patient's response and adverse reaction conditions can help achieve a clinical cure. Patients with low baseline HBV DNA and low HBsAg levels at 48 weeks achieve HBsAg clearance more quickly than other populations.
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http://dx.doi.org/10.1016/j.ijid.2020.05.041DOI Listing
July 2020

LncRNA AATBC regulates Pinin to promote metastasis in nasopharyngeal carcinoma.

Mol Oncol 2020 09 13;14(9):2251-2270. Epub 2020 Jun 13.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Long noncoding RNA (lncRNA) have emerged as crucial regulators for a myriad of biological processes, and perturbations in their cellular expression levels have often been associated with cancer pathogenesis. In this study, we identified AATBC (apoptosis-associated transcript in bladder cancer, LOC284837) as a novel lncRNA. AATBC was found to be highly expressed in nasopharyngeal carcinoma (NPC), and increased AATBC expression was associated with poor survival in patients with NPC. Furthermore, AATBC promoted migration and invasion of NPC cells in vitro, as well as metastasis in vivo. AATBC upregulated the expression of the desmosome-associated protein pinin (PNN) through miR-1237-3p sponging. In turn, PNN interacted with the epithelial-mesenchymal transition (EMT) activator ZEB1 and upregulated ZEB1 expression to promote EMT in NPC cells. Collectively, our results indicate that AATBC promotes NPC progression through the miR-1237-3p-PNN-ZEB1 axis. Our findings indicate AATBC as a potential prognostic biomarker or therapeutic target in NPC.
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http://dx.doi.org/10.1002/1878-0261.12703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463349PMC
September 2020

Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell proliferation through the LOC553103-STMN1 axis.

FASEB J 2020 06 18;34(6):8012-8027. Epub 2020 Apr 18.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Epstein-Barr virus (EBV) is a tumorigenic virus that can cause various human malignancies such as nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV encodes 44 mature micro (mi)RNAs, mostly exhibiting oncogenic properties and promoting cancer progression. However, we have previously found that one EBV-encoded miRNA, namely EBV-miR-BART6-3p, acts as a tumor suppressor by inhibiting metastasis and invasion. Here, we report that EBV-miR-BART6-3p inhibits the proliferation of EBV-associated cancers, NPC, and GC, by targeting and downregulating a long non-coding RNA (lncRNA), LOC553103. Through proteomics analysis, we determined that stathmin (STMN1) is affected by EBV-miR-BART6-3p and LOC553103. Further, via RNA immunoprecipitation and luciferase reporter assay, we confirmed that LOC553103 directly binds and stabilizes the 3'UTR region of STMN1 mRNA. These results indicate that the EBV-miR-BART6-3p/LOC553103/STMN1 axis regulates the expression of cell cycle-associated proteins, which then inhibit EBV-associated tumor cell proliferation. These findings provide potential targets or strategies for novel EBV-related cancer treatments, as well as contributes new insights into the understanding of EBV infection-related carcinogenesis.
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http://dx.doi.org/10.1096/fj.202000039RRDOI Listing
June 2020

Gossypol induces apoptosis of multiple myeloma cells through the JUN-JNK pathway.

Am J Cancer Res 2020 1;10(3):870-883. Epub 2020 Mar 1.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University Changsha 410078, Hunan, China.

Multiple myeloma (MM) is one of the most common hematologic neoplastic diseases. Gossypol was once used as a male contraceptive but is considered a novel antitumor agent. This study aimed to reveal the gossypol-induced apoptosis mechanism and its hub genes. Gossypol-induced MM cell apoptosis is concentration- and time-dependent. Of a total of 532 differentially expressed genes, 273 genes were upregulated and 259 genes were downregulated in gossypol-treated MM cells. Through KEGG and WGCNA analyses, the apoptosis-associated module was identified, and was identified as the hub gene. The expression of the protein product c-Jun was downregulated in MM cell lines compared to that in normal plasma cells. High-risk MM patients had a lower expression of . High-expression group patients had a lower risk of death. overexpression in MM cells induced potent cell death and growth inhibition by a caspase-dependent apoptotic mechanism. is one of the upstream receptors of the JNK pathway, and shRNA knockdown of can partially reverse gossypol-induced apoptosis. A total of 1017 genes were coexpressed with in MM patients. These genes are mainly involved in other JNK-associated signaling pathways, such as the , and signaling pathways. In conclusion, is identified as the hub gene in gossypol-induced apoptosis, and gossypol can activate caspase-dependent apoptosis through the JNK pathway by targeting c-Jun and other JNK-associated pathways. and are also involved in this mechanism.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136925PMC
March 2020

Single cell RNA-seq reveals the landscape of tumor and infiltrating immune cells in nasopharyngeal carcinoma.

Cancer Lett 2020 05 13;477:131-143. Epub 2020 Feb 13.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China. Electronic address:

Nasopharyngeal carcinoma (NPC) is one of the most malignant tumors in Southern China and southeast Asia, which is characterized by a dense lymphocyte infiltration and a poor prognosis. The emergence of single-cell sequencing represents a powerful tool to resolve tumor heterogeneity and delineate the complex communication among the tumor cells with neighboring stromal and immune cells in the tumor microenvironment (TME). Here, we performed single cell RNA-seq and analyzed tumor cells together with the infiltrating immune cells from three NPC tumor tissues. In our study, the malignant cells display the intra- and inter-tumoral heterogeneity among the individual patients. Analysis of the immune cells reveal the heterogeneous composition of the distinct immune cells and the various functional states of T cells in NPC tumors. Additionally, coupled with the reconstruct of the T cell receptor (TCR) sequences from immune cells full-length single-cell sequence data, we identify the diverse T cell clonotypes and expansion distribution in individual tumors. Overall, we firstly reveal the landscape of tumor and infiltrating immune cells in nasopharyngeal cancer. These results provide deeper insights on the mechanisms of tumor clearance by immune cells in the surrounding microenvironment, which will be helpful in improving the targeted and immune therapies for NPC.
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http://dx.doi.org/10.1016/j.canlet.2020.02.010DOI Listing
May 2020

Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA.

Mol Cancer 2020 02 4;19(1):22. Epub 2020 Feb 4.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Non-coding RNAs do not encode proteins and regulate various oncological processes. They are also important potential cancer diagnostic and prognostic biomarkers. Bioinformatics and translation omics have begun to elucidate the roles and modes of action of the functional peptides encoded by ncRNA. Here, recent advances in long non-coding RNA (lncRNA) and circular RNA (circRNA)-encoded small peptides are compiled and synthesized. We introduce both the computational and analytical methods used to forecast prospective ncRNAs encoding oncologically functional oligopeptides. We also present numerous specific lncRNA and circRNA-encoded proteins and their cancer-promoting or cancer-inhibiting molecular mechanisms. This information may expedite the discovery, development, and optimization of novel and efficacious cancer diagnostic, therapeutic, and prognostic protein-based tools derived from non-coding RNAs. The role of ncRNA-encoding functional peptides has promising application perspectives and potential challenges in cancer research. The aim of this review is to provide a theoretical basis and relevant references, which may promote the discovery of more functional peptides encoded by ncRNAs, and further develop novel anticancer therapeutic targets, as well as diagnostic and prognostic cancer markers.
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http://dx.doi.org/10.1186/s12943-020-1147-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998289PMC
February 2020

Biogenic volatile organic compound emissions from Pinus massoniana and Schima superba seedlings: Their responses to foliar and soil application of nitrogen.

Sci Total Environ 2020 Feb 26;705:135761. Epub 2019 Nov 26.

Fujian Provincial Key Laboratory of Soil Environmental Health and Regulation, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address:

Increasing nitrogen (N) deposition is one of the main drivers of global change, while the emission of biogenic volatile organic compounds (BVOCs) from plant in response to elevated N deposition is poorly understood, especially with respect to the response to foliar application of N. In this study, BVOC emissions from two tree species (Pinus massoniana Lamb. and Schima superba Gardn. et Champ.) were determined by dynamic chamber coupled with a proton transfer reaction-time of flight-mass spectrometer. Two N application methods, namely soil application of N (SAN) and foliar application of N (FAN), and three N levels (5.6, 15.6 and 20.6 g N m yr) were employed by applying NHNO every week for 1.5 years. The results showed that: (1) oxygenated volatile organic compounds (OVOCs, mainly acetaldehyde, methyl alcohol, ethenone and acetone) and non-methane hydrocarbons (NMHCs, mainly monoterpenes, propyne, 1,3-butadiene and propylene) were the dominant BVOCs for all the treatments, accounting for 32.40-65.72% and 19.21-47.39% of total 100 determined BVOC compounds, respectively; (2) for S. superba seedlings, both SAN and FAN treatments significantly decreased total BVOC emissions (11.83% to 66.23%). However, total BVOCs from P. massoniana significantly increased with N addition for SAN treatment, while no difference were found in the FAN treatment; (3) BVOC emission rates for FAN treatment were significantly lower than those for SAN treatment, indicating that previous studies which simulated N deposition by adding N directly to soil might have imprecisely estimated their effects on plant BVOC emissions. Considering the inconsistent responses of BVOC emissions to different N application methods for different plant species, close attention should be paid on the effects of N deposition or even global change on plant BVOC emissions in the future.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135761DOI Listing
February 2020

The Accumulated Response of Deciduous Hance and Evergreen Thunb. Seedlings to Simulated Nitrogen Additions.

Front Plant Sci 2019 20;10:1596. Epub 2019 Dec 20.

College of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua, China.

Nitrogen depositions in the Yangtze River Delta have is thought to shift the coexistence of mixed evergreen and deciduous species. In this study, the seedlings of the dominant evergreen species Thunb. and the deciduous species Hance from the Yangtze River Delta were chosen to test their responses to simulated N additions using an ecophysiological approach. N was added to the tree canopy at rates of 0 (CK), 25 kg N ha year (N25), and 50 kg N ha year (N50). The leaf N content per mass (, by 44.03 and 49.46%) and total leaf chlorophyll content (, by 72.15 and 63.63%) were enhanced for both species, and but not tended to allocate more N to per leaf area (with a higher slope). The enhanced N availability and promoted the apparent quantum yield () significantly by 15.38 and 43.90% for and , respectively. Hydraulically, the increase in sapwood density () for was almost double that of . Synchronous improved sapwood specific hydraulic conductivity (, by 37.5%) for induced a significant reduction in stomatal conductance () ( < 0.05) in the N50 treatments, which is in contrast to the weak varied accompanied by a 59.49% increase in for . As a result, the elevated maximum photosynthesis () of 12.19% for in combination with the increase in the total leaf area (indicated by a 37.82% increase in the leaf area ratio-leaf area divided by total aboveground biomass) ultimately yielded a 34.34% enhancement of total biomass. In contrast, the and total biomass were weakly promoted for . The reason for these distinct responses may be attributed to the lower water potential at 50% of conductivity lost () for , which enables higher hydraulic safety at the cost of a weak increase in A due to the stomatal limitation in response to elevated N availability. Altogether, our results indicate that the deciduous would be more susceptible to elevated N availability even if both species received similar N allocation.
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http://dx.doi.org/10.3389/fpls.2019.01596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933011PMC
December 2019