Publications by authors named "Qingwei Meng"

128 Publications

High BASP1 Expression is Associated with Poor Prognosis and Promotes Tumor Progression in Human Lung Adenocarcinoma.

Cancer Invest 2021 Apr 4:1-20. Epub 2021 Apr 4.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, P.R. China.

BASP1 is involved in signal transduction and cytoskeleton formation and plays a tumor-promoting or tumor-suppressing role in cancers. We found BASP1 was overexpressed in lung adenocarcinoma tissues and promoted the proliferation and migration of lung adenocarcinoma cells. The mechanism may be related to inhibition of cell apoptosis and abnormal activation of the Wnt/β-catenin pathway and epithelial mesenchymal transformation. BASP1 is associated with poor prognosis in lung adenocarcinoma.
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http://dx.doi.org/10.1080/07357907.2021.1910290DOI Listing
April 2021

CXCR1 correlates to poor outcomes of EGFR-TKI against advanced non-small cell lung cancer by activating chemokine and JAK/STAT pathway.

Pulm Pharmacol Ther 2021 Apr 11;67:102001. Epub 2021 Feb 11.

The Third Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, China. Electronic address:

Objective: CXCR1, a member of the seven-transmembrane chemokine receptor family, promotes cell proliferation and metastasis in many tumors. The present study was undertaken to explore the interrelation between CXCR1 expression and the prognosis of advanced non-small cell lung cancer (NSCLC) in addition to the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma (LUAD).

Methods: The expression of CXCR1 in NSCLC tissues was assessed by immunohistochemistry. The relationships between CXCR1 expression and clinical-pathological factors were investigated. Concomitantly, the relationship between CXCR1 expression and EGFR-TKI treatment efficacy was investigated. Gene set enrichment analysis (GSEA) was employed for the exploration of pathway enrichment, tumor immune estimation resource (TIMER) and gene expression profiling interactive analysis (GEPIA) for the inspection of the interrelationship between infiltration immune cells and CXCR1. After gain-and loss-of-function of CXCR1 in NSCLC cells, qRT-PCR and Western blot were applied to measure the levels of proteins associated with the chemokine pathway (CCL3 and CXCL2) and the JAK/STAT pathway (IL9R, PIAS4 and STAT5A).

Results: CXCR1 significantly correlated with poor prognosis of NSCLC patients. Additionally, CXCR1 limited the clinical efficacy of EGFR-TKIs in advanced LUAD (P = 0.029). In the tumor microenvironment, CXCR1 was positively associated with infiltration levels of immune markers in lung squamous cell carcinoma (LUSC) and LUAD. High expression of CXCR1 was implicated in the NOD-like receptor (NLR), cytokine/cytokine receptor, JAK/STAT and chemokine signaling pathways in LUAD and LUSC. Overexpression of CXCR1 in NSCLC cell lines enhanced expressions of CCL3, CXCL2, IL9R, PIAS4 and STAT5A, while knockdown of CXCR1 repressed expressions of CCL3, CXCL2, IL9R, PIAS4 and STAT5A.

Conclusion: CXCR1 is correlated with poor prognosis of NSCLC and affects the efficacy of EGFR-TKIs in LUAD.
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http://dx.doi.org/10.1016/j.pupt.2021.102001DOI Listing
April 2021

Correction: Tumor-associated macrophages promote tumor metastasis via the TGF-β/SOX9 axis in non-small cell lung cancer.

Oncotarget 2020 Dec 29;11(52):4845-4846. Epub 2020 Dec 29.

The Sixth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

[This corrects the article DOI: 10.18632/oncotarget.21068.].
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http://dx.doi.org/10.18632/oncotarget.27740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779255PMC
December 2020

Sirtuin 1 promotes autophagy and proliferation of endometrial cancer cells by reducing acetylation level of LC3.

Cell Biol Int 2021 Jan 12. Epub 2021 Jan 12.

Department of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Endometrial cancer (EC) constitutes a common female genital tract tumor with a rising incidence rate. Sirtuin 1 (SIRT1) is a member of histone deacetylase, which extensively participates in the progression of aging, cell death, and tumorigenesis. This study explored the effect of SIRT1-mediated LC3 acetylation on autophagy and proliferation of EC cells. SIRT1 expression in EC tissues and adjacent tissues, EC cell lines and normal human epithelial cells was detected. SIRT1 expression was elevated in EC cell lines and tissues. Knockdown of SIRT1 inhibited proliferation, migration, and invasion of EC cells. Then, EC cells were starved in serum-free medium, and levels of autophagy-related proteins were detected. Starvation induced autophagy of EC cells. The starvation-treated EC cells showed an increased SIRT1 expression, a decreased LC3 acetylation level and an increased autophagy level. The proliferation and autophagy of EC cells under different treatments were evaluated. In EC cells transfected with overexpressing SIRT1, LC3 acetylation was inhibited and cell proliferation was promoted. Moreover, overexpressing SIRT1 facilitated growth and autophagy of transplanted tumors in nude mice. In conclusion, SIRT1 promoted autophagy and proliferation of EC cells by reducing acetylation level of LC3.
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http://dx.doi.org/10.1002/cbin.11549DOI Listing
January 2021

Systematic Analysis of Expression Profiles and Prognostic Significance for Family in Non-small-Cell Lung Cancer.

Front Mol Biosci 2020 10;7:572406. Epub 2020 Dec 10.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

Background: Lung cancer remains a common malignancy and the leading cause of cancer-related deaths in the world. Although dramatic progress made in multimodal therapies, it still has a poor prognosis. The Family with sequence similarity 83 () of poorly characterized proteins are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini, most of which significantly elevated levels of expression in multiple cancers. However, the expression and prognostic values of different family in lung cancer, especially in non-small-cell lung cancer (NSCLC), have not been clarified.

Methods: ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, cBioPortal, and STRING databases were utilized in this study.

Results: The transcriptional levels of A/B/C/D/F/G/H were up-regulated in patients with NSCLC. A noticeable correlation was found between the over-expressions of and clinical cancer stages in NSCLC patients. Besides, higher mRNA expressions of were discovered to be expressively associated with overall survival (OS) in lung cancer patients, furthermore, , , and in OS group achieved 0.9475/1, 0.971897/1, and 0.9454545/0.8974359 specificity/sensitivity in distinguishing short survivors from long survivors, respectively. Moreover, a high mutation rate of family (51%) was also observed in lung adenocarcinoma (LUAD) patients, and genetic alteration in the family was associated with shorter OS and disease-free survival (DFS) in LUAD patients.

Conclusion: Our results indicated that might play important roles in NSCLC tumorigenesis and might be risk factor for the survival of NSCLC patients.
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http://dx.doi.org/10.3389/fmolb.2020.572406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758490PMC
December 2020

SlWHY2 interacts with SlRECA2 to maintain mitochondrial function under drought stress in tomato.

Plant Sci 2020 Dec 12;301:110674. Epub 2020 Sep 12.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai' an, Shandong 271018, China. Electronic address:

Drought stress in plants leads to inhibition of photosynthesis and respiration, accumulation of reactive oxygen species (ROS), and reprogramming of gene expression. Here, we established that the tomato (Solanum lycopersicum) WHIRLY2 (SlWHY2) gene, which encodes a mitochondrial single-stranded DNA-binding protein, was significantly induced by drought stress. Under drought conditions, SlWHY2 RNAi plants showed more wilting and lower fresh weight, chlorophyll content, quantum yield of photosystem I (PSI; YI), and maximal photochemical efficiency of PSII (Fv/Fm) than the wild type (WT). Drought treatment also caused the SlWHY2 RNAi lines to accumulate more ROS than the WT, and the silenced lines had lower AOX (alternative oxidase) activity. As expected, the mitochondrial membrane potential (MMP) was less stable in the SlWHY2 RNAi lines. The expression levels of seven genes in the mitochondrial genome (SYCF15, NAD7, NAD4, COS2, COX1, COX2, and COX3) were decreased even more in the SlWHY2 RNAi lines than they were in the WT under drought stress. SlWHY2 interacted directly in vivo and in vitro with SlRECA2, a mitochondrial recombinase A that is important for mitochondrial DNA recombination and repair. These results suggest that SlWHY2 plays an essential role in maintaining mitochondrial function and enhancing drought tolerance in tomato.
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http://dx.doi.org/10.1016/j.plantsci.2020.110674DOI Listing
December 2020

SlSGRL, a tomato SGR-like protein, promotes chlorophyll degradation downstream of the ABA signaling pathway.

Plant Physiol Biochem 2020 Dec 29;157:316-327. Epub 2020 Oct 29.

State Key Laboratory of Crop Biology, College of Life Science, Shandong Agricultural University, Daizong Street, Tai'an 271018, Shandong, PR China. Electronic address:

Chlorophyll (chl) degradation plays a vital role during green plant growth and development, including nutrient metabolism, fruit and seed maturation, and phototoxic detoxification. STAY-GREEN (SGR) is a plant-specific regulator involved in chl degradation. Previous studies showed that SlSGR1 functioned in chl degradation and lycopene accumulation during fruit ripening of tomato (Solanum lycopersicum). However, little is known about SlSGR-LIKE (SlSGRL) gene, which is a homolog of SlSGR1. We cloned the SlSGRL gene and created transgenic tomato plants overexpressing (OE) SlSGRL. Expression analysis showed that SlSGRL was up-regulated by abscisic acid (ABA). Our data showed that SlSGRL-OE lines exhibited earlier leaf yellowing than wild-type (WT) lines under ABA treatment. Yeast two-hybrid (Y2H) assay revealed that SlSGRL interacted with pheophytin pheophorbide hydrolase (SlPPH) and light-harvesting complex a2 (SlLHCa2) to promote the chl degradation. Further analysis demonstrated that ABA-INSENSITIVE5 (SlABI5) and SlABI5-LIKE regulated SlSGRL expression by directly binding to the sequence (-611 to -582) of the SlSGRL promoter that included an ABRE cis-element. We proposed that SlSGRL, which was regulated by SlABI5/SlABI5-LIKE, mainly acted in ABA-induced chl degradation via interacting with SlPPH and SlLHCa2.
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http://dx.doi.org/10.1016/j.plaphy.2020.10.028DOI Listing
December 2020

High prognostic nutritional index (PNI) as a positive prognostic indicator for non-small cell lung cancer patients with bone metastasis.

Clin Respir J 2021 Feb 10;15(2):225-231. Epub 2020 Dec 10.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

Introduction: Increasing evidence shows the close association between prognostic nutritional index (PNI) and overall survival (OS) of solid cancers including lung cancer. However, the role of PNI in non-small cell lung cancer patients (NSCLC) with bone metastasis remains unclear.

Objective: To explore the prognostic role of PNI in NSCLC patients with bone metastasis.

Methods: A retrospective analysis of 259 initially diagnosed NSCLC with bone metastasis was conducted. Univariate and multivariate analysis were used to assess the potential prognostic roles of parameters.

Results: The most common symptoms initially presented were cough and chest pain. Two hundred patients (77.2%) received the treatment of bisphosphonates. Patients with low PNI were found in 154 (59.5%) patients. Median survival time for all cases was 286 days. The median OS for patients with low and high PNI was 227 and 389 days, respectively. The 6-month, 1-year and 2-year survival rates for patients with low PNI were 66.2%, 29.9% and 10.4% compared to 79.0%, 52.4% and 26.7% in patients with high PNI level. On univariate analysis, female patients, non-smokers, high PNI and systematic chemotherapy (P < 0.05) were shown to be closely correlated with a better prognosis of NSCLC patients with bone metastasis. Only PNI (P = 0.002), systematic chemotherapy (P = 0.026) and distant metastasis number (P = 0.044) held statistical significance on multivariate analysis.

Conclusions: PNI represents a non-invasive, efficiency and convenient biomarker of NSCLC patients with bone metastasis. High PNI, systematic chemotherapy and distant metastasis number <2 are independent positive prognostic factors of NSCLC patients with bone metastasis.
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http://dx.doi.org/10.1111/crj.13288DOI Listing
February 2021

Roles of stay-green (SGR) homologs during chlorophyll degradation in green plants.

Bot Stud 2020 Sep 23;61(1):25. Epub 2020 Sep 23.

State Key Laboratory of Crop Biology, College of Life Science, Shandong Agricultural University, Daizong Street, Tai'an, 271018, Shandong, People's Republic of China.

Chlorophyll (Chl) degradation is one of the most obvious signs of leaf senescence and fruit ripening. Stay-green (SGR) homologs that can remove magnesium from Chl a are the most important components in Chl degradation pathway in green plants. SGR homologs are not only universally involved in Chl breakdown during the senescence of green organs, but also play crucial roles in other organs during plant growth and development, such as fruit mature and nodule development. In this review, we focus on the diverse functions of SGR homologs in plant growth and development. A better understanding of SGR would be helpful for providing a theoretical basis for further illustrating the regulatory mechanism of SGR homologs.
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http://dx.doi.org/10.1186/s40529-020-00302-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511501PMC
September 2020

The roles of chloroplast membrane lipids in abiotic stress responses.

Plant Signal Behav 2020 11 20;15(11):1807152. Epub 2020 Aug 20.

Shandong Provincial Key Laboratory of Plant Stress, College of Life Sciences, Shandong Normal University , Jinan, Shandong, China.

Plant chloroplasts have complex membrane systems. Among these, thylakoids serve as the sites for photosynthesis and photosynthesis-related adaptation. In addition to the photosynthetic membrane complexes and associated molecules, lipids in the thylakoid membranes, are predominantly composed of MGDG (monogalactosyldiacylglycerol), DGDG (digalactosyldiacylglycerol), SQDG (sulfoquinovosyldiacylglycerol) and PG (phosphatidylglycerol), play essential roles in shaping the thylakoid architecture, electron transfer, and photoregulation. In this review, we discuss the effect of abiotic stress on chloroplast structure, the changes in membrane lipid composition, and the degree of unsaturation of fatty acids. Advanced understanding of the mechanisms regulating chloroplast membrane lipids and unsaturated fatty acids in response to abiotic stresses is indispensable for improving plant resistance and may inform the strategies of crop breeding.
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http://dx.doi.org/10.1080/15592324.2020.1807152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588187PMC
November 2020

Effect of dietary pyrroloquinoline quinone disodium in sows on intestinal health of the offspring.

Food Funct 2020 Sep;11(9):7804-7816

Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, People's Republic of China.

The objective of this study was to investigate the effects of dietary pyrroloquinoline quinone disodium (PQQ·Na2) supplementation in sows during gestation and lactation on intestinal health in offspring. A total of 40 cross-bred (landrace × large white crossed with Duroc boar) multiparity gestation sows with an average parity of 4.3 were used in this study. Forty sows were allotted to 2 dietary treatments after breeding. One group was the control sows, which were fed a corn-soybean meal control diet (Con treatment, n = 20), and the other group was the treatment sows fed a control diet with 20 mg kg-1 PQQ·Na2 after breeding and through gestation and lactation (PQQ treatment, n = 20). The activities of SOD and GSH-Px were significantly (P < 0.05) increased by PQQ·Na2 supplementation, and MDA activity was decreased (P < 0.05) in the plasma of piglets. CAT, SOD and GSH-Px activities were significantly (P < 0.05) increased, and MDA activity was decreased (P < 0.05) in the small intestine of piglets. The mRNA expression levels of SOD1, CAT and MGST1 in the jejunum were increased in newborn piglets (P < 0.05), and the mRNA expression levels of HO1, SOD1, CAT, SOD2, GPX4, GPX1 and GCLC in the jejunum were increased in weaned piglets (P < 0.05). The mRNA expression of ZO-1 was increased (P < 0.05) in the jejunum of newborn piglets, and the mRNA expression of Occludin and ZO-1 was increased (P < 0.05) in the jejunum of weaned piglets. The villous height of the duodenum and jejunum of weaned piglets was increased (P < 0.05) by dietary PQQ·Na2. In weaned piglets, Bacteroidetes and Firmicutes were the most prevalent phyla in both the Con and PQQ·Na2 treatment groups, and the most prevalent genera were Alloprevotella and Bacteroides. At the phylum level, the abundance of Firmicutes was significantly increased (P < 0.05), and the abundance of Proteobacteria was significantly decreased (P < 0.05). At the genus level, the abundance of Alloprevotella was significantly increased (P < 0.05), and the abundance of Actinobacillus and Escherichia was decreased (P < 0.05). In conclusion, dietary supplementation with PQQ·Na2 in sows during gestation and lactation had positive effects on intestinal health in offspring.
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http://dx.doi.org/10.1039/d0fo01403fDOI Listing
September 2020

The role of NAC transcription factor in plant cold response.

Plant Signal Behav 2020 09 14;15(9):1785668. Epub 2020 Jul 14.

State Key Laboratory of Crop Biology, College of Life Science, Shandong Agricultural University , Tai'an, Shandong, China.

The NAC transcription factor (TF) is one of the largest families of TFs in plants and plays an important role in plant growth, development, and response to environmental stress. The structural and functional characteristics of NAC TFs have been uncovered in the past years, including sequence binding features of the DNA-binding domain located in the N-terminus and dynamic interplay between the domain located at the C-terminus and other proteins. Studies on NAC TF are increasing in number; these studies distinctly contribute to our understanding of the regulatory networks of NAC-mediated complex signaling and transcriptional reprogramming. Previous studies have indicated that NAC TFs are key regulators of the plant stress response. However, these studies have been for six years so far and mainly focused on drought and salt stress. There are relatively few reports about NAC TFs in plant cold signal pathway and no related reviews have been published. In this review article, we summarize the structural features of NAC TFs, the target genes, upstream regulators and interaction proteins of stress-responsive NAC TFs, and the roles NAC TFs play in plant cold stress signal pathway.
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http://dx.doi.org/10.1080/15592324.2020.1785668DOI Listing
September 2020

Corrigendum to "Macrophages induce EMT to promote invasion of lung cancer cells through the IL-6-mediated COX-2/PGE/β-catenin signalling pathway" [Mol. Immunol. 90 (2017) 197-210].

Mol Immunol 2020 10 4;126:165-166. Epub 2020 Jul 4.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road 150 of Nangang District, Harbin, Heilongjiang Province 150081, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.molimm.2020.06.021DOI Listing
October 2020

Dual Single-Atomic Ni-N and Fe-N Sites Constructing Janus Hollow Graphene for Selective Oxygen Electrocatalysis.

Adv Mater 2020 Jul 22;32(30):e2003134. Epub 2020 Jun 22.

Discipline of Chemistry, University of Newcastle, Callaghan, NSW, 2308, Australia.

Nitrogen-coordinated metal single atoms in carbon have aroused extensive interest recently and have been growing as an active research frontier in a wide range of key renewable energy reactions and devices. Herein, a step-by-step self-assembly strategy is developed to allocate nickel (Ni) and iron (Fe) single atoms respectively on the inner and outer walls of graphene hollow nanospheres (GHSs), realizing separate-sided different single-atom functionalization of hollow graphene. The Ni or Fe single atom is demonstrated to be coordinated with four N atoms via the formation of a Ni-N or Fe-N planar configuration. The developed Ni-N /GHSs/Fe-N Janus material exhibits excellent bifunctional electrocatalytic performance, in which the outer Fe-N clusters dominantly contribute to high activity toward the oxygen reduction reaction (ORR), while the inner Ni-N clusters are responsible for excellent activity toward the oxygen evolution reaction (OER). Density functional theory calculations demonstrate the structures and reactivities of Fe-N and Ni-N for the ORR and OER. The Ni-N /GHSs/Fe-N endows a rechargeable Zn-air battery with excellent energy efficiency and cycling stability as an air-cathode, outperforming that of the benchmark Pt/C+RuO air-cathode. The current work paves a new avenue for precise control of single-atom sites on carbon surface for the high-performance and selective electrocatalysts.
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http://dx.doi.org/10.1002/adma.202003134DOI Listing
July 2020

PpAOX regulates ER stress tolerance in Physcomitrella patens.

J Plant Physiol 2020 Aug 11;251:153218. Epub 2020 Jun 11.

Key Laboratory of Bio-resource and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, China. Electronic address:

Severe environments disturb the folding or assembly of newly synthesized proteins, resulting in accumulation of misfolded or unfolded proteins in the endoplasmic reticulum (ER) as well as cytotoxic aggregation of abnormal proteins. Therefore, ER stress is evoked due to disturbed ER homeostasis. Alternative oxidase (AOX) plays an important role in coping with various abiotic stresses and plant growth. Our previous study has reported that PpAOX is involved in the regulation of salt tolerance in moss Physcomitrella patens (P. patens), but its biological functions in modulating ER stress remain unknown. Here we report that the gametophyte of P. patens displays severe growth inhibition and developmental deficiency under tunicamycin (Tm, an elicitor of ER stress)-induced ER stress conditions. PpAOX and selected ER stress response-like genes in P. patens were induced under Tm treatment. PpAOX knockout (PpAOX KO) plants exhibited decreased resistance to Tm-induced ER stress, whereas PpAOX-overexpressing lines (PpAOX OX) plants were more tolerant to Tm-induced ER stress. Data showed that PpAOX contributes to redox homeostasis under Tm treatment. In addition, we observed that PpAOX completely restores the Tm-sensitive phenotype of Arabidopsis AOX1a mutant (Ataox1a). Taken together, our work reveals a functional link between PpAOX and ER stress tolerance regulation in P. patens.
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http://dx.doi.org/10.1016/j.jplph.2020.153218DOI Listing
August 2020

FAM83A drives PD-L1 expression via ERK signaling and FAM83A/PD-L1 co-expression correlates with poor prognosis in lung adenocarcinoma.

Int J Clin Oncol 2020 Sep 19;25(9):1612-1623. Epub 2020 May 19.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China.

Purpose: The purpose of this research was to explore the correlation and prognostic significance of FAM83A and programmed cell death-ligand 1 (PD-L1) protein expression in patients with lung adenocarcinoma (LUAD).

Methods: A total of 130 LUAD specimens and 50 normal lung tissue specimens were analyzed for both FAM83A and PD-L1 expression by immunohistochemistry (IHC) analysis. The effect of FAM83A on PD-L1 and ERK pathway was evaluated by RT-PCR and western blot in vitro.

Results: Both FAM83A and PD-L1 were upregulated in patients with LUAD and co-expression of them was significantly associated with tumor stage, metastasis and worse survival in LUAD. Multivariate cox regression analysis revealed that co-expression of FAM83A and PD-L1 was an independent prognostic factor impacting survival. Moreover, experiments in vitro showed FAM83A could promote the expression of PD-L1 through the ERK pathway.

Conclusion: FAM83A and PD-L1 may be potential therapeutic targets for LUAD. Co-expression of FAM83A and PD-L1 in tumor cells was a credible biomarker predictor for worse survival in resected cases. FAM83A may promote the expression of PD-L1 through ERK signaling pathway, thus causing immune escape of tumor.
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http://dx.doi.org/10.1007/s10147-020-01696-9DOI Listing
September 2020

Effects of dietary resveratrol supplementation in sows on antioxidative status, myofiber characteristic and meat quality of offspring.

Meat Sci 2020 Sep 5;167:108176. Epub 2020 May 5.

Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

This study investigated the influence of dietary resveratrol (300 mg/kg) supplementation in sows on the antioxidative status, myofiber characteristic and meat quality of their progeny. Results showed that maternal dietary resveratrol supplementation increased (P < 0.05) the backfat thickness and tended (P = 0.055) to increase the intramuscular fat of finishing pigs. The drip loss and lactic acid level were reduced, and the pH of longissimus thoracis was increased by maternal dietary resveratrol supplementation (P < 0.05). Maternal dietary resveratrol supplementation increased the mRNA and protein expression of MyHC I and decreased the mRNA and protein expression of MyHC IIb in the longissimus thoracis (P < 0.05). The malonaldehyde (MDA) level in longissimus thoracis was reduced and the superoxide dismutase (SOD) activity and SOD2 mRNA expression were increased by maternal dietary resveratrol supplementation (P < 0.05). In conclusion, dietary resveratrol supplementation in sows improves the meat quality of offspring by altering the myofiber characteristic and antioxidative status.
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http://dx.doi.org/10.1016/j.meatsci.2020.108176DOI Listing
September 2020

Reference genome and annotation updates lead to contradictory prognostic predictions in gene expression signatures: a case study of resected stage I lung adenocarcinoma.

Brief Bioinform 2020 May 8. Epub 2020 May 8.

RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20-v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.
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http://dx.doi.org/10.1093/bib/bbaa081DOI Listing
May 2020

Weaning Alters Intestinal Gene Expression Involved in Nutrient Metabolism by Shaping Gut Microbiota in Pigs.

Front Microbiol 2020 17;11:694. Epub 2020 Apr 17.

Institute of Animal Nutrition, Northeast Agricultural University, Harbin, China.

Weaning transition usually impairs intestinal architecture and functions and results in gut-associated disorders in pigs. Understanding the changes in intestinal transcriptome and gut microbiota during weaning transition is important for elucidating the underlying mechanism of weaning stress. In the present study, we performed RNA-seq to determine the changes in intestinal transcriptome and 16S rRNA sequencing to measure the gut microbiota changes in the weaning transition. Transcriptome results indicated that weaning transition altered intestinal gene expression involved in nutrient transport and metabolism. Regarding fatty metabolism, fatty acid-binding protein 1 (), acyl-CoA dehydrogenase (), and carnitine palmitoyltransferase 2 () expression in the intestine was decreased by weaning. Genes related to bile acid metabolism were increased by weaning, including , farnesoid X receptor ( or ) and organic solute transporter-α (). In addition, genes associated with oxidative stress were altered by weaning transition, including decreased catalase () and lactate dehydrogenase () and increased glutathione peroxidase 2 () and superoxide dismutase 3 (). Results of microbiota composition showed that the Firmicutes abundance and Firmicutes/Bacteroidetes ratio were increased and that the Proteobacteria abundance in the fecal microbiota was decreased by the weaning process; during the weaning transition, the and abundances decreased markedly, and these bacteria nearly disappeared, while the abundance showed a marked increase. Moreover, the levels of the microbial metabolites butyrate and acetate increased with changes in gut microbiota composition. In addition, predictive metagenome by PICRUSt analysis showed that the pathways related to D-glutamine and D-glutamate metabolism, citrate cycle (TCA cycle), peroxisome proliferators-activated receptor (PPAR) signaling, alpha-linolenic acid metabolism were decreased and the pathway related to retinol metabolism was increased in the gut microbiota of piglets during weaning transition. Our results showed that early weaning alters intestinal gene expression involved in nutrient metabolism, which may be due to the changes in microbiota composition.
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http://dx.doi.org/10.3389/fmicb.2020.00694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181064PMC
April 2020

Threonine, but Not Lysine and Methionine, Reduces Fat Accumulation by Regulating Lipid Metabolism in Obese Mice.

J Agric Food Chem 2020 Apr 15;68(17):4876-4883. Epub 2020 Apr 15.

Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, China.

Some amino acids (AAs) have been proven to suppress fat mass and improve insulin sensitivity. However, the impact of important essential AAs, threonine, lysine, and methionine, on obesity has not been clarified. In the present study, after an 8 week period of obesity induction, mice were grouped to receive either a high-fat diet (HFD) or HFD supplemented with lysine, threonine, or methionine (3% in drinking water) for another 10 weeks. The results showed that dietary supplementation with threonine significantly decreased body weight, epididymal and perirenal fat pad weights, serum concentrations of glucose, triacylglycerols, total cholesterol, and LDL-cholesterol compared to the HFD group. HOMA-IR and serum leptin and adiponectin were improved by threonine supplementation. In epididymal adipose tissue, threonine treatment significantly down-regulated the expression levels of lipogenesis and up-regulated expressions of lipolysis compared to the HFD group. Threonine addition stimulated the expression of UCP-1 and related genes in brown adipose tissue. However, lysine or methionine supplementation showed little effect on body weight, WAT weight, serum lipid profiles, and lipid-metabolism-related gene expressions of HFD-fed mice. These findings suggest that threonine inhibited fat mass and improved lipid metabolism of already obese mice, providing a potential agent in treating obesity.
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http://dx.doi.org/10.1021/acs.jafc.0c01023DOI Listing
April 2020

WHIRLY1 maintains leaf photosynthetic capacity in tomato by regulating the expression of RbcS1 under chilling stress.

J Exp Bot 2020 06;71(12):3653-3663

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai' an, Shandong, China.

Rubisco, which consists of eight large subunits (RBCLs) and eight small subunits (RBCSs), is a major photosynthetic enzyme that is sensitive to chilling stress. However, it is largely unclear how plants maintain high Rubisco content under low temperature conditions. Here, we report that tomato WHIRLY1 (SlWHY1) positively regulates the Rubisco level under chilling stress by directly binding to the promoter region of SlRbcS1, resulting in the activation of SlRbcS1 expression. SlRbcS1-overexpressing lines had higher Rubisco contents and were more resistant to chilling stress compared with the wild type. Quantitative real-time PCR analyses showed that, among the five RbcS genes, only SlRbcS1 expression is up-regulated by chilling treatment. These results indicate that SlWHIRLY1 specifically enhances the levels of SlRbcS1 and confers tolerance to chilling stress. The amino acid sequence of SlRBCS1 shows 92.67% identity with those of another two RBCS proteins and three residues are specifically found in SlRBCS1. However, mutation of these residues to alanine in SlRBCS1 does not influence its function during cold adaptation. Thus, we conclude that high levels of Rubisco, but not the specific residues in SlRBCS1, play important roles in tolerance to chilling stress in tomato.
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http://dx.doi.org/10.1093/jxb/eraa145DOI Listing
June 2020

Visible light-mediated selective α-functionalization of 1,3-dicarbonyl compounds via disulfide induced aerobic oxidation.

Chem Commun (Camb) 2019 Oct;55(86):13008-13011

State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, 116024, P. R. China.

A visible light-mediated α-functionalization of 1,3-dicarbonyl compounds with switchable selectivity induced by disulfide is disclosed. Upon irradiation with visible light, the metal- and base-free α-hydroxylation or α-hydroxymethylation reaction proceeded smoothly through a disulfide-catalyzed oxidation under mild conditions. The combination of a continuous-flow strategy could further improve the reaction efficiencies.
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http://dx.doi.org/10.1039/c9cc06544jDOI Listing
October 2019

WHIRLY1 Regulates HSP21.5A Expression to Promote Thermotolerance in Tomato.

Plant Cell Physiol 2020 Jan;61(1):169-177

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, Shandong 271018, China.

Heat stress poses a major threat to plant productivity and crop yields. The induction of heat shock proteins (HSPs) by heat shock factors is a principal defense response of plants exposed to heat stress. In this study, we identified and analyzed the heat stress-induced Whirly1 (SlWHY1) gene in tomato (Solanum lycopersicum). We generated various SlWHY1-overexpressing (OE) and SlWHY1-RNA interference (RNAi) lines to investigate the role of WHIRLY1 in thermotolerance. Compared with the wild type (WT), the OE lines showed less wilting, as reflected by their increased membrane stability and soluble sugar content and reduced reactive oxygen species (ROS) accumulation under heat stress. By contrast, RNAi lines with inhibited SlWHY1 expression showed the opposite phenotype and corresponding physiological indices under heat stress. The heat-induced gene SlHSP21.5A, encoding an endoplasmic reticulum-localized HSP, was upregulated in the OE lines and downregulated in the RNAi lines compared with the WT. RNAi-mediated inhibition of SlHSP21.5A expression also resulted in reduced membrane stability and soluble sugar content and increased ROS accumulation under heat stress compared with the WT. SlWHY1 binds to the elicitor response element-like element in the promoter of SlHSP21.5A to activate its transcription. These findings suggest that SlWHY1 promotes thermotolerance in tomato by regulating SlHSP21.5A expression.
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http://dx.doi.org/10.1093/pcp/pcz189DOI Listing
January 2020

Effect of fermented blood cells on growth performance and intestinal characteristics of weaned piglets.

J Anim Physiol Anim Nutr (Berl) 2019 Nov 4;103(6):1875-1884. Epub 2019 Sep 4.

Institute of Animal Nutrition, Northeast Agricultural University, Harbin, China.

The increase in feed costs has led feeder to replace protein source. Blood meal can be used in piglet diets instead of fish meal (FM). The objective of this study was to investigate the effect of fermented blood cells (FBCs) on the growth performance and intestinal health of weaned piglets. One hundred eighty 28-day-old piglets were assigned and were divided into 4 groups (9 L per groups and 5 pigs per litters) randomly. The piglets were fed one of four experimental diets, fish meal, blood cells (BCs), liquid-state fermented blood cells (LFBCs) or solid-state fermented blood cells (SFBCs) respectively. The dietary with LFBCs and SFBCs increased the average daily gain and feed intake (ADFI) and average daily gain (ADG) (p < .05). In duodenum, LFBC group increased the villous height (p < .05). The SFBC and LFBC group significantly increased the villous height (p < .05) in the jejunum. Fermented blood cells exhibit a positive regulatory function on the intestinal tract and modulate intestinal microflora. Compared with the fish meal group, the CAT, GSH-PX and SOD activity, and MDA level was no significant differences in jejunum and plasma of weaned piglets (p > .05). LFBCs and SFBCs significantly increased the bifidobacteria and lactobacillus number in the caecum (p < .05). Dietary LFBCs increased the expression of ZO-1 mRNA in the jejunal of weaned piglets (p < .05). In conclusion, dietary with fermented blood cells in weaned piglets had improved growth performance and intestinal health of weaned piglets.
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http://dx.doi.org/10.1111/jpn.13194DOI Listing
November 2019

FAM83A signaling induces epithelial-mesenchymal transition by the PI3K/AKT/Snail pathway in NSCLC.

Aging (Albany NY) 2019 08 24;11(16):6069-6088. Epub 2019 Aug 24.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China.

Family with sequence similarity 83, member A (FAM83A), as a potential tumor promoter, was reported to contribute to the progression of several malignant tumors. However, the significance of FAM83A in invasion and metastasis of non-small cell lung cancer (NSCLC) remains largely unknown. In this study, we found that FAM83A expression was significantly increased in NSCLC tissues. High expression of FAM83A was positively associated with tumor metastasis and poor survival of NSCLC patients. Functional experiments revealed that FAM83A knockdown could suppress NSCLC cell migration and invasion both and . While opposite results were observed in FAM83A-transfected cells. Mechanically, we found that FAM83A promoted NSCLC cell migration and invasion by inducing epithelial-mesenchymal transition (EMT) via PI3K/ATK/Snail signaling. Rescue experiment demonstrated that inhibition of either AKT or Snail could partially counteract the promoting effect of FAM83A overexpression in NSCLC metastasis. Taken together, our findings are the first time to demonstrate that increased expression of FAM83A in NSCLC was correlated with EMT and tumor metastasis, which may provide a novel therapeutic target in NSCLC treatment.
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http://dx.doi.org/10.18632/aging.102163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738414PMC
August 2019

Maternal dietary resveratrol alleviates weaning-associated diarrhea and intestinal inflammation in pig offspring by changing intestinal gene expression and microbiota.

Food Funct 2019 Sep 21;10(9):5626-5643. Epub 2019 Aug 21.

Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.

Early weaning commonly results in gastrointestinal disorders, inflammation and diarrhea in infants and young animals. Resveratrol, a plant phenol, affords protection against inflammation and cancer. A porcine model was used to investigate the effects of maternal dietary resveratrol on diarrhea, intestinal inflammation and the intestinal morphology in offspring during weaning. The results showed that maternal dietary resveratrol alleviated weaning-associated intestinal inflammation and diarrhea and improved the intestinal morphology in offspring. In weaning piglets, maternal dietary resveratrol increased the proportion of butyrate-producing bacteria, such as Flavonifractor, Odoribacter and Oscillibacter, as determined by 16S rRNA sequencing. RNA-seq analysis identified 189 and 139 differentially expressed genes (DEGs) in weaning and post-weaning piglets, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs were enriched for the T cell receptor, primary immunodeficiency, mitogen-activated protein kinase (MAPK) and Ras signaling pathways in weaning piglets and for the cytokine-cytokine receptor interaction pathway and metabolism-related pathways in post-weaning piglets.
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http://dx.doi.org/10.1039/c9fo00637kDOI Listing
September 2019

Transcriptome analysis of the effect of pyrroloquinoline quinone disodium (PQQ·Na) on reproductive performance in sows during gestation and lactation.

J Anim Sci Biotechnol 2019 7;10:62. Epub 2019 Aug 7.

Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030 People's Republic of China.

Background: Pyrroloquinoline quinone (PQQ), which is a water soluble, thermo-stable triglyceride-quinone, is widely distributed in nature and characterized as a mammalian vitamin-like redox cofactor. The objective of this study was to investigate the effects of pyrroloquinoline quinone disodium (PQQ·Na) on reproductive performance in sows.

Results: Dietary supplementation with PQQ·Na significantly increased the total number of piglets born, the number of piglets born alive and the born alive litter weight. It also increased the antioxidant status in the placenta, plasma and milk. The concentration of NO was significantly increased in the plasma and placenta. RNA-seq analysis showed that 462 unigenes were differentially expressed between the control (Con) treatment and PQQ treatment groups. Among these unigenes, 199 were upregulated, while 263 unigenes were downregulated. The assigned functions of the unigenes covered a broad range of GO categories. Reproduction (27, 7.03%) and the reproduction process (27, 7.03%) were assigned to the biological process category. By matching DEGs to the KEGG database, we identified 29 pathways.

Conclusions: In conclusion, dietary supplementation with PQQ·Na in gestating and lactating sows had positive effects on their reproductive performance.
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http://dx.doi.org/10.1186/s40104-019-0369-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685232PMC
August 2019

TBL1XR1 is involved in c-Met-mediated tumorigenesis of human nonsmall cell lung cancer.

Cancer Gene Ther 2020 04 27;27(3-4):136-146. Epub 2019 Jun 27.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150081, Harbin, China.

Nonsmall cell lung carcinoma (NSCLC) contributes to the highest number of cancer deaths globally. Metastases and chemoresistance are two major confounders to the treatment efficacy in NSCLC. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been associated with high rates of metastases in breast, gastric, and stomach cancers. However, the role of TBL1XR1 in lung cancers remains underexplored. We selected matched and cancerous lung tissues to establish the upregulation of TBL1XR1. Using in vitro assays, we assessed the influence of TBL1XR1 on various cancer phenotypes, namely cell proliferation, chemoresistance, invasion, and metastases in a CRISPR-Cas9-mediated knock out model (A549 cells), and H460 cell lines overexpressing TBL1XR1. We found that TBL1XR1 is overexpressed in NSCLC tissue and patient sera in comparison to paired adjacent normal tissue. Overexpression of TBL1XR1 in NSCLC cell lines mediates cell survival, proliferation, and metastases. TBL1XR1 was found to regulate MEK and Akt pathways through their master regulator c-Met. We observed that activation of c-Met is downregulated in the absence of TBL1XR1. Our study strengthens the contention that TBL1XR1 is a biomarker for prognosis of NSCLC. It may also be considered as an adjunct or core therapeutic target to overcome cisplatin resistance in lung cancers.
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http://dx.doi.org/10.1038/s41417-019-0111-0DOI Listing
April 2020

Mammalian Eps15 homology domain 1 potentiates angiogenesis of non-small cell lung cancer by regulating β2AR signaling.

J Exp Clin Cancer Res 2019 Apr 25;38(1):174. Epub 2019 Apr 25.

The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.

Background: Non-small cell lung cancer (NSCLC) is a devastating disease with a heterogeneous prognosis, and the molecular mechanisms underlying tumor progression remain elusive. Mammalian Eps15 homology domain 1 (EHD1) plays a promotive role in tumor progression, but its role in cancer angiogenesis remains unknown. This study thus explored the role of EHD1 in angiogenesis in NSCLC.

Methods: The changes in angiogenesis were evaluated through human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation assays. The impact of EHD1 on β2-adrenoceptor (β2AR) signaling was evaluated by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and enzyme-linked immunosorbent assay (ELISA). The interaction between EHD1 and β2AR was confirmed by immunofluorescence (IF) and coimmunoprecipitation (Co-IP) experiments, and confocal microscopy immunofluorescence studies revealed that β2AR colocalized with the recycling endosome marker Rab11, which indicated β2AR endocytosis. Xenograft tumor models were used to investigate the role of EHD1 in NSCLC tumor growth.

Results: The microarray analysis revealed that EHD1 was significantly correlated with tumor angiogenesis, and loss- and gain-of-function experiments demonstrated that EHD1 potentiates HUVEC proliferation, migration and tube formation. EHD1 knockdown inhibited β2AR signaling activity, and EHD1 upregulation promoted vascular endothelial growth factor A (VEGFA) and β2AR expression. Interestingly, EHD1 interacted with β2AR and played a novel and critical role in β2AR endocytic recycling to prevent receptor degradation. Aberrant VEGFA or β2AR expression significantly affected EHD1-mediated tumor angiogenesis. The proangiogenic role of EHD1 was confirmed in xenograft tumor models, and immunohistochemistry (IHC) analysis confirmed that EHD1 expression was positively correlated with VEGFA expression, microvessel density (MVD) and β2AR expression in patient specimens.

Conclusion: Collectively, the data obtained in this study suggest that EHD1 plays a critical role in NSCLC angiogenesis via β2AR signaling and highlight a potential target for antiangiogenic therapy.
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http://dx.doi.org/10.1186/s13046-019-1162-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482525PMC
April 2019

Preparation of O-Protected Cyanohydrins by Aerobic Oxidation of α-Substituted Malononitriles in the Presence of Diarylphosphine Oxides.

Org Lett 2019 04 28;21(8):2597-2601. Epub 2019 Mar 28.

Department of Pharmaceutics , Harbin Medical University (Daqing) , Daqing 163319 , China.

A mild, reagent-cyanide-free, and efficient synthesis of O-phosphinoyl-protected cyanohydrins from readily available α-substituted malononitriles was realized using diarylphosphine oxides in the presence of O. Mechanistic studies indicated that in addition to the initial aerobic oxidation of the malononitrile derivative notable features of this process include the formation of a tetrahedral intermediate and a subsequent intramolecular rearrangement. The phosphinoyl-protecting group can be removed by alcoholysis or by reduction with DIBAL-H.
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http://dx.doi.org/10.1021/acs.orglett.9b00569DOI Listing
April 2019