Publications by authors named "Qi Cheng"

385 Publications

Correction to: Top-down Modulation of Outcome Processing in Primary Sensory Cortex for Flexible Behavior.

Neurosci Bull 2021 May 9. Epub 2021 May 9.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Center for Brain Science and Brain-Inspired Technology, Shanghai, 200031, China.

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http://dx.doi.org/10.1007/s12264-021-00695-8DOI Listing
May 2021

LILRA3 is related to monocyte-derived dendritic cell maturation and activation.

Iran J Basic Med Sci 2021 Feb;24(2):196-202

Department of Rheumatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.

Objectives: Previously we reported functional leukocyte immunoglobulin-like receptor A3 () leads to susceptibility and sub-phenotypes of several autoimmune diseases. LILRA3 levels in blood serum and CD14 monocytes enhanced in systemic lupus erythematosus and resulted in disease severity. However, the mechanism of LILRA3 in the pathogenesis of autoimmunity remains elusive. This study aims to explore the potential impact of LILRA3 on the differentiation, maturation, and function of monocyte-derived DCs (MoDCs).

Materials And Methods: The human monocytic cell line (THP-1) was cultured to derive MoDCs in vitro. We performed plasmid transfection to examine the impact of LILRA3 on monocyte differentiation. Surface markers on MoDCs were measured using FACS. To assess the function of mature MoDCs, IL-12p70, IFN-γ and IL-4 levels were detected after the mixed leucocyte response by enzyme-linked immunosorbent assay. Western blot assay was employed in this study to determine the signaling pathways in MoDCs activation.

Results: LILRA3 promotes MoDCs maturation, our results showed significant up-regulation of CD40, CD80, CD86, CD209, and HLA-DR and increased production of pro-inflammatory cytokine IL-12. LILRA3-treated MoDCs exhibited a robust proliferation of allogeneic CD4 T cells and induced naïve CD4 T cell polarization into the Th1 phenotype. Furthermore, the preceding activation of MoDCs maturation and LILRA3 function might be attributed to p38 MAPK and STAT1 signaling pathway's aberrant activation.

Conclusion: This is the first study to report that LILRA3 played a critical role in promoting MoDCs maturation and directing MoDCs to modulate Th1 cell differentiation, which may have a role in the pathogenesis of autoimmune diseases.
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http://dx.doi.org/10.22038/ijbms.2020.50714.11555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061320PMC
February 2021

The crosstalk network of XIST/miR-424-5p/OGT mediates RAF1 glycosylation and participates in the progression of liver cancer.

Liver Int 2021 Apr 28. Epub 2021 Apr 28.

Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, P.R. China.

Background: Liver cancer is a major public health concern, but the mechanistic actions of bio-markers contributing to liver cancer remain to be determined. In this study, we aimed to investigate the regulatory cascade of microRNA-424-5p (miR-424-5p), X-inactive-specific transcript (XIST), and O-GlcNAc transferase (OGT) in liver cancer.

Methods: Differentially expressed miRNAs and target genes related to liver cancer were predicted by bioinformatic analyses, and their expression was determined in liver tissues of patients with liver cancer and liver cancer cells. The RNA immunoprecipitation (RIP), RNA pull-down, and dual luciferase reporter assay were used to examine the binding affinity among XIST and miR-424-5p and OGT. Then, gain- and loss- of function assays were conducted to evaluate the effects of the XIST/miR-424-5p/OGT axis on malignant phenotypes. A nude mouse model of liver cancer was further established for in vivo substantiation.

Results: XIST and OGT were up-regulated in liver cancer tissues and cells, responsible for poor prognosis in patients with liver cancer, while miR-424-5p was down-regulated. XIST competitively bound to miR-424-5p to increase OGT expression. XIST silencing inhibited malignant phenotypes of liver cancer cells, while miR-424-5p downregulation negated its effect.. miR-424-5p suppressed RAF1 glycosylation by negatively regulating OGT expression and promoted its ubiquitination/degradation. Further, XIST knockdown inhibited tumor growth and metastasis in nude mice, while ectopic OGT reversed its effect.

Conclusion: These results reveal a novel mechanism by which the interaction of XIST/miR-424-5p/OGT participates in the malignancy and metastasis of liver cancer.
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http://dx.doi.org/10.1111/liv.14904DOI Listing
April 2021

Health benefits of wolfberry (Gou Qi Zi, L.) on the basis of ancient Chineseherbalism and Western modern medicine.

Avicenna J Phytomed 2021 Mar-Apr;11(2):109-119

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Objective: Goji berry has been used for thousand years inTraditional Chinese Medicine (TCM) in China and other Asian countries as foods to promote health and as drugs to treat diseases. It has been claimed this important medicinal crop is the good source of compounds with valuable nutritional and bioactive properties which can also provide industrial sustainability in organic life.

Materials And Methods: All relevant papers in English language were collected. The keywords of wolfberry, goji berry, Chinese herbalism and western Medicine were searched in Google Scholar, Scopus, Research Gate and PubMed.

Results: Besides its uses in food and culinary, wolfberry has long played important roles in TCM where they are believed to enhance immune system function, improve eyesight, protect liver, boost sperm production and improve circulation, among other effects. TCM calls for wolfberry to be prepared as a decoction or ground into a powder and mixed with other herbs. Additionally, Gojiberry is rich in ascorbic acid, thiamine and riboflavin. Moreover, Gojiberrycontains carbohydrates, organic acids, and so many minerals like potassium, sodium, phosphorus, magnesium, iron, calcium, zinc and selenium.

Conclusion: This review article allowed verifying that wolfberry as asource of compounds with valuable nutritional and bioactive properties.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051317PMC
April 2021

Erastin synergizes with cisplatin via ferroptosis to inhibit ovarian cancer growth in vitro and in vivo.

J Obstet Gynaecol Res 2021 Apr 21. Epub 2021 Apr 21.

Department of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, China.

Aim: Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment or serious side effects often occurs in ovarian cancer, and thus, there is an urgent need for effective and combined therapies to overcome such obstacles. In the present study, we aimed to uncover synergistic effects between erastin and cisplatin (CDDP) in inhibiting ovarian cancer cell growth by inducing ferroptosis in vitro and in vivo.

Methods: We performed a CCK-8 assay to detect cell viability in response to erastin alone or in combination with cisplatin and provided further confirmation by western blotting analysis. Transmission electron microscopy and flow cytometry analysis were used to depict the characteristics of ferroptosis. In addition, an ovarian cancer tumor xenograft was built to verify the effects in vivo.

Results: CDDP induced multiple modes of cell death-including ferroptosis in ovarian cancer cell lines. Mechanistically, erastin triggered ferroptosis and increased the levels of reactive oxygen species (ROS) so as to augment the cytotoxic effect of cisplatin. Combination therapy based on CDDP and erastin appeared to maximize the therapeutic effects while minimizing side effects in ovarian cancer both in vitro and in vivo.

Conclusion: Collectively, our results indicate that erastin works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS-mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.
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http://dx.doi.org/10.1111/jog.14779DOI Listing
April 2021

Effects of simulated COVID-19 cytokine storm on stent thrombogenicity.

Cardiovasc Revasc Med 2021 Apr 8. Epub 2021 Apr 8.

CVPath Institute, Inc., 19 Firstfield Road, Gaithersburg, MD 20878, United States of America. Electronic address:

Background: Cytokine storm-related hypercoagulation may be important in the pathogenesis of stent thrombosis in patients with SARS-CoV-2. Whether stent polymers behave differently under such conditions has never been explored.

Methods: Fluorinated polymer-nanocoated and uncoated COBRA stents (CeloNova), BioLinx-polymer-coated Resolute Onyx stents (Medtronic), and Synergy stents (Boston Scientific), which are abluminally coated with a bioabsorbable polymer, were exposed to human blood from healthy donors which was supplemented with 400 pg/mL IL-6 and 100 pg/mL TNF-α, similar to what is seen in cytokine storm caused by SARS-CoV-2. Platelet adhesion and neutrophil activation, assessed by immunofluorescence, were compared under cytokine storm and control conditions (untreated blood) (n = 4 experimental runs).

Results: Platelet adhesion values, defined as %platelet-covered area x staining intensity, were significantly lower in coated and uncoated COBRA and in Resolute Onyx than in Synergy under control conditions (1.28 × 10 ± 0.43 × 10 vs. 2.92 × 10 ± 0.49 × 10 vs. 3.57 × 10 ± 0.73 × 10 vs. 9.94 × 10 ± 0.99 × 10; p ≤0.0001). In cytokine storm, platelet adhesion values remained low in coated COBRA-PzF (1.78 × 10 ± 0.38 × 10) compared to all other devices (uncoated COBRA: 5.92 × 10 ± 0.96 × 10; Resolute Onyx: 7.27 × 10 ± 1.82 × 10; Synergy: 11.28 × 10 ± 1.08 × 10; p ≤ 0.0001). Although cytokine storm conditions significantly increased neutrophil activation in all stents, it was significantly less in coated and uncoated COBRA, and in Resolute Onyx than in Synergy.

Conclusions: Blood-biomaterials interactions may determine the thrombogenic potential of stents. Under simulated cytokine storm conditions, fluoropolymer-coated stents showed the most favorable anti-thrombogenic and anti-inflammatory properties.
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http://dx.doi.org/10.1016/j.carrev.2021.03.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026249PMC
April 2021

Top-down Modulation of Outcome Processing in Primary Sensory Cortex for Flexible Behavior.

Neurosci Bull 2021 Mar 20. Epub 2021 Mar 20.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Center for Brain Science and Brain-Inspired Technology, Shanghai, 200031, China.

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http://dx.doi.org/10.1007/s12264-021-00656-1DOI Listing
March 2021

Sensitive periods in cortical specialization for language: insights from studies with Deaf and blind individuals.

Curr Opin Behav Sci 2020 Dec 1;36:169-176. Epub 2020 Dec 1.

Johns Hopkins University.

Studies with Deaf and blind individuals demonstrate that linguistic and sensory experiences during sensitive periods have potent effects on neurocognitive basis of language. Native users of sign and spoken languages recruit similar fronto-temporal systems during language processing. By contrast, delays in sign language access impact proficiency and the neural basis of language. Analogously, early but not late-onset blindness modifies the neural basis of language. People born blind recruit 'visual' areas during language processing, show reduced left-lateralization of language and enhanced performance on some language tasks. Sensitive period plasticity in and outside fronto-temporal language systems shapes the neural basis of language.
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http://dx.doi.org/10.1016/j.cobeha.2020.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945734PMC
December 2020

Effects of BMP-2 compound with fibrin on osteoporotic vertebral fracture healing in rats.

J Musculoskelet Neuronal Interact 2021 03;21(1):149-156

Department of Orthopedic Surgery, Xuzhou Third Hospital, Affiliated Xuzhou Hospital of Jiangsu University, Xuzhou, China.

Objectives: To investigate the effects of bone morphogenetic protein-2 (BMP-2) compound with fibrin on osteoporotic vertebral fracture healing in rats.

Methods: For the present study 160 Specific-Pathogen Free 32-week-old female Sprague-Dawley rats were used. 120 rats were randomly divided in three groups (experimental, model and sham operation group- n=40 per group) and were ovariectomized to establish the osteoporosis model. 40 rats served as a control group without treatment. The expression of BMP-2 in the fracture zone at the 4th, 6th, 8th, and 12th weeks was detected by qRT-PCR. The expression of BALP and CTX-I in serum at the 12th week was detected by Elisa.

Results: At week 8, the morphology of the sham operation group was the same and the fracture healing occurred more slowly than in the other groups. At week 12, the expression of BMP-2 in the model group was significantly higher than that in the other three groups (p<0.05). At week 12, the maximum load, maximum strain, and elastic modulus of model group were significantly lower than those of the other three groups.

Conclusions: BMP-2 compound with fibrin can enhance the timing and quality of bone fracture healing in rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020021PMC
March 2021

High expression of ENPP1 in high-grade serous ovarian carcinoma predicts poor prognosis and as a molecular therapy target.

PLoS One 2021 26;16(2):e0245733. Epub 2021 Feb 26.

Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China.

Recent studies have shown that the expression of ENPP1 is related to differentiation, death, dissemination and chemosensitivity of tumor cells. So far, there is no research in ovarian carcinoma. This study aimed at exploring the role of ENPP1 gene in ovarian carcinoma, the relationship with prognostic indicators and chemotherapy resistance, and investigates the possibility of molecular targeted therapy. The expression of ENPP1 in 41 normal ovarian epithelial tissues, 97 ovarian serous cystadenoma and 103 HGSOC tissues was detected by IHC. In ovarian cancer tissues and ovarian cancer cell lines, mRNA and protein expression of ENPP1 was determined by qRT-PCR and Western blot. The ENPP1 expression was knockdowned by siRNA. Cell proliferation was measured with the BrdU Cell Proliferation ELISA. Cell migration and invasion were detected by Wound-Healing, Transwell migration and Matrigel invasion assay. Caspase 3 activity was determined by the CaspACE. The expression of EMT markers such as E-cadherin, N-cadherin, and Vimentin was measured, and the expression of PCNA and MMP9 was also be detected. The results showed that the expression of ENPP1 was significantly increased in high-grade ovarian serous carcinoma, the number of strong expression was 85.4% (22.3%+63.1%) and only 1.03% (1.03%+0.0%) in serous cystadenoma, but no in normal ovarian epithelium (P< 0.05). And the stronger the expression of ENPP1, the later the FIGO stage and the poorer differentiation of cells (P = 0.001 or <0.001, respectively). However, no correlation was found between the expression of ENPP1 and chemosensitivity. ENPP1 was also highly expressed in ovarian cancer tissues and in epithelial ovarian cancer cell lines (A2780, CaoV3, OVCAR3, SKOV3 and 3ao). After down-regulation of ENPP1 expression by RNA interference, the cell proliferation, migration and invasion of ovarian cancer cell decreased significantly, the expression of apoptosis related gene caspase 3 increased significantly, while the expression of PCNA and MMP9 was significantly down regulated. In addition, EMT biological characteristics of A2780 and SKOV3 cells were also inhibited. In summary, the increased expression of ENPP1 may be related to the occurrence of HGSOC, and indicate that the disease progresses rapidly and the prognosis is poor. ENPP1 may be considered as a potential molecular therapeutic target.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245733PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909685PMC
February 2021

Targeting stemness of cancer stem cells to fight colorectal cancers.

Semin Cancer Biol 2021 Feb 22. Epub 2021 Feb 22.

The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China. Electronic address:

Cancer initiating/ stem cells (CSCs) undergo self-renewal and differentiation that contributes to tumor initiation, recurrence and metastasis in colorectal cancer (CRC). Targeting of colorectal cancer stem cells (CCSCs) holds significant promise in eradicating cancer cells and ultimately curing patients with cancer. In this review, we will introduce the current progress of CCSC studies, including the specific surface markers of CCSCs, the intrinsic signaling pathways that regulate the stemness and differentiation characteristics of CCSCs, and the tumor organoid model for CCSC research. We will focus on how these studies will lead to the progress in targeting specific surface markers or signaling pathways on CCSCs by monoclonal antibodies, or by natural or synthetic compounds, or by immunotherapy. As CSCs are highly heterogeneous and plastic, we suggest that combinatory approaches that target the stemness network may represent an important strategy for eradicating cancers.
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http://dx.doi.org/10.1016/j.semcancer.2021.02.012DOI Listing
February 2021

Highly sensitive nanoparticle sensing based on a hybrid cavity in a freely suspended microfiber.

Nanotechnology 2021 May;32(20):205203

Measurement Technology and Instrumentation Key Lab of Hebei Province, Yanshan University, Qinhuangdao 066004, People's Republic of China.

We report a hybrid cavity structure based on a suspended microfiber with a diameter of 1.7 μm applied to nanoparticle sensing in water. The proposed hybrid cavity is composed of two symmetrical reflectors with a slotted Au layer in the middle. After being characterized by the finite-difference time-domain method, the obtained strong reflection and sufficiently wide band gap provide the potential to realize an ultrasmall mode volume, which can improve sensitivity and lower loss. In addition, an ultrahigh Q/V ratio of 8.2 × 10 (λ/n) and high resonance transmittance of T = 0.53 can be obtained through optimization analysis. After analyzing the trapping force and resonance shift caused by the change in local electric field, it is proven that our proposed cavity exhibits a high sensitivity and offers a convenient and stable method for particle sensing in water.
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http://dx.doi.org/10.1088/1361-6528/abe48eDOI Listing
May 2021

Three hematologic/immune system-specific expressed genes are considered as the potential biomarkers for the diagnosis of early rheumatoid arthritis through bioinformatics analysis.

J Transl Med 2021 01 6;19(1):18. Epub 2021 Jan 6.

Department of Rheumatology, the Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.

Background: Rheumatoid arthritis (RA) is the most common chronic autoimmune connective tissue disease. However, early RA is difficult to diagnose due to the lack of effective biomarkers. This study aimed to identify new biomarkers and mechanisms for RA disease progression at the transcriptome level through a combination of microarray and bioinformatics analyses.

Methods: Microarray datasets for synovial tissue in RA or osteoarthritis (OA) were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by R software. Tissue/organ-specific genes were recognized by BioGPS. Enrichment analyses were performed and protein-protein interaction (PPI) networks were constructed to understand the functions and enriched pathways of DEGs and to identify hub genes. Cytoscape was used to construct the co-expressed network and competitive endogenous RNA (ceRNA) networks. Biomarkers with high diagnostic value for the early diagnosis of RA were validated by GEO datasets. The ggpubr package was used to perform statistical analyses with Student's t-test.

Results: A total of 275 DEGs were identified between 16 RA samples and 10 OA samples from the datasets GSE77298 and GSE82107. Among these DEGs, 71 tissue/organ-specific expressed genes were recognized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEGs are mostly enriched in immune response, immune-related biological process, immune system, and cytokine signal pathways. Fifteen hub genes and gene cluster modules were identified by Cytoscape. Eight haematologic/immune system-specific expressed hub genes were verified by GEO datasets. GZMA, PRC1, and TTK may be potential biomarkers for diagnosis of early RA. NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158- miR-212-3p/miR-132-3p/miR-129-5p-TTK might be potential RNA regulatory pathways to regulate the disease progression of early RA.

Conclusions: This work identified three haematologic/immune system-specific expressed genes, namely, GZMA, PRC1, and TTK, as potential biomarkers for the early diagnosis and treatment of RA and provided insight into the mechanisms of disease development in RA at the transcriptome level. In addition, we proposed that NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158-miR-212-3p/miR-132-3p/miR-129-5p-TTK are potential RNA regulatory pathways that control disease progression in early RA.
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http://dx.doi.org/10.1186/s12967-020-02689-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789535PMC
January 2021

An efficient method for building a database of diatom populations for drowning site inference using a deep learning algorithm.

Int J Legal Med 2021 May 3;135(3):817-827. Epub 2021 Jan 3.

Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice, Shanghai, People's Republic of China.

Seasonal or monthly databases of the diatom populations in specific bodies of water are needed to infer the drowning site of a drowned body. However, existing diatom testing methods are laborious, time-consuming, and costly and usually require specific expertise. In this study, we developed an artificial intelligence (AI)-based system as a substitute for manual morphological examination capable of identifying and classifying diatoms at the species level. Within two days, the system collected information on diatom profiles in the Huangpu and Suzhou Rivers of Shanghai, China. In an animal experiment, the similarities of diatom profiles between lung tissues and water samples were evaluated through a modified Jensen-Shannon (JS) divergence measure for drowning site inference, reaching a prediction accuracy of 92.31%. Considering its high efficiency and simplicity, our proposed method is believed to be more applicable than existing methods for seasonal or monthly water monitoring of diatom populations from sections of interconnected rivers, which would help police narrow the investigation scope to confirm the identity of an immersed body.
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http://dx.doi.org/10.1007/s00414-020-02497-5DOI Listing
May 2021

Environment and host species identity shape gut microbiota diversity in sympatric herbivorous mammals.

Microb Biotechnol 2020 Dec 26. Epub 2020 Dec 26.

Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai, 810008, China.

The previous studies have reported that the mammalian gut microbiota is a physiological consequence; nonetheless, the factors influencing its composition and function remain unclear. In this study, to evaluate the contributions of the host and environment to the gut microbiota, we conducted a sequencing analysis of 16S rDNA and shotgun metagenomic DNA from plateau pikas and yaks, two sympatric herbivorous mammals, and further compared the sequences in summer and winter. The results revealed that both pikas and yaks harboured considerably more distinct communities between summer and winter. We detected the over-representation of Verrucomicrobia and Proteobacteria in pikas, and Archaea and Bacteroidetes in yaks. Firmicutes and Actinobacteria, associated with energy-efficient acquisition, significantly enriched in winter. The diversity of the microbial community was determined by the interactive effects between the host and season. Metagenomic analysis revealed that methane-metabolism-related pathway of yaks was significantly enriched in summer, while some pathogenic pathways were more abundant in pikas. Both pikas and yaks had a higher capacity for lipid degradation in winter. Pika and yak shared more OTUs when food shortage occurred in winter, and this caused a convergence in gut microbial composition and function. From winter to summer, the network module number increased from one to five in pikas, which was different in yaks. Our study demonstrates that the host is a dominant factor in shaping the microbial communities and that seasonality promotes divergence or convergence based on dietary quality across host species identity.
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http://dx.doi.org/10.1111/1751-7915.13687DOI Listing
December 2020

Association between circadian rhythm disruption and polycystic ovary syndrome.

Fertil Steril 2021 Mar 24;115(3):771-781. Epub 2020 Dec 24.

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Institute for Women's Health, University College London, London, United Kingdom. Electronic address:

Objective: To explore the association of circadian rhythm disruption with polycystic ovary syndrome (PCOS) and the potential underlying mechanism in ovarian granulosa cells (GCs).

Design: Multicenter questionnaire-based survey, in vivo and ex vivo studies.

Setting: Twelve hospitals in China, animal research center, and research laboratory of a women's hospital.

Patients/animals: A total of 436 PCOS case subjects and 715 control subjects were recruited for the survey. In vivo and ex vivo studies were conducted in PCOS-model rats and on ovarian GCs collected from women with PCOS and control subjects.

Intervention(s): The PCOS rat model was established with the use of testosterone propionate.

Main Outcome Measure(s): Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), RNA sequencing, rhythmicity analysis, functional enrichment analysis.

Result(s): There was a significant correlation between night shift work and PCOS. PCOS-model rats presented distinct differences in the circadian variation of corticotropin-releasing hormone, adrenocorticotropic hormone, prolactin, and a 4-h phase delay in thyrotropic hormone levels. The motif enrichment analysis of ATAC-seq revealed the absence of clock-related transcription factors in specific peaks of PCOS group, and RNA sequencing ex vivo at various time points over 24 hours demonstrated the differential rhythmic expression patterns of women with PCOS. Kyoto Encyclopedia of Genes and Genomes analysis further highlighted metabolic dysfunction, including both carbohydrate and amino acid metabolism and the tricarboxylic acid cycle.

Conclusion(s): There is a significant association of night shift work with PCOS, and genome-wide chronodisruption exists in ovarian GCs.
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http://dx.doi.org/10.1016/j.fertnstert.2020.08.1425DOI Listing
March 2021

Clinical serum metabolomics study on fluoxetine hydrochloride for depression.

Neurosci Lett 2021 02 19;746:135585. Epub 2020 Dec 19.

Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, China. Electronic address:

Background: Fluoxetine hydrochloride is one of the familiar antidepressants of the second generation and has the effect of inhibiting the reuptake of 5-hydroxytryptamine by central nervous system. Both clinical trials and animal experiments show that it has good antidepressant effect, but there are few reports on its clinical efficacy in treating depression patients from the perspective of metabolomics. This study aimed at evaluating the antidepressant effect of fluoxetine hydrochloride by metabolomics, so that to find out its specific biomarkers and related metabolic characteristics of depression in the treatment of depression and analyze the intervention mechanism of fluoxetine hydrochloride in depression.

Method: Twenty depression patients and twenty healthy volunteers were recruited in clinical. Using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to analyze serum metabolites of depression patients pretherapy and post-treatment and compared with healthy people.

Result: Finally, we have detected 16 specific biomarkers of depression. Compared with the healthy group, the level of 10 biomarkers in the depression group was significantly increased (P < 0.05) and 6 biomarkers were significantly decreased (P < 0.01). After 8 weeks of fluoxetine hydrochloride treatment, all the biomarkers have showed a tendency of callback. The metabolic pathways involved amino acid metabolism, energy metabolism and lipid metabolism.

Conclusion: In our study, the antidepressant effect of fluoxetine hydrochloride in clinic was proved by metabolomics and provided basis for clinical use of fluoxetine hydrochloride. At the same time, the biomarkers that may be related to the occurrence of depression are determined to provide objective basis for the diagnosis of depression.
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http://dx.doi.org/10.1016/j.neulet.2020.135585DOI Listing
February 2021

Traditional herbal medicines to overcome stress, anxiety and improve mental health in outbreaks of human coronaviruses.

Phytother Res 2021 Mar 22;35(3):1237-1247. Epub 2020 Dec 22.

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.

Mental health condition is including depression and anxiety, and they may impact wellbeing, personal relationships and productivity of both genders. Herbal medicines have been used to treatment of anxiety and depression symptoms for centuries. SARS, MERS and COVID-19 are related to coronavirus types. SARS (sever acute respiratory syndrome, China, 2002), MERS (Middle East respiratory syndrome, Saudi Arabia, 2012), and SARS-CoV-2 (2019-2020) are the main coronavirus outbreaks. Both anxiety and depression are more serious to be considered and improved for all general public during fight with these diseases. In this mini-review article, we have mentioned the key role some of the most important plants and herbs for treatment of stress and anxiety and improve mental health against SARS and SARS-CoV-2 on the basis of traditional Asian medicine, especially traditional Chinese and Persian medicine.
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http://dx.doi.org/10.1002/ptr.6888DOI Listing
March 2021

When event knowledge overrides word order in sentence comprehension: Learning a first language after childhood.

Dev Sci 2020 Dec 9:e13073. Epub 2020 Dec 9.

University of California, San Diego, La Jolla, CA, USA.

Limited language experience in childhood is common among deaf individuals, which prior research has shown to lead to low levels of language processing. Although basic structures such as word order have been found to be resilient to conditions of sparse language input in early life, whether they are robust to conditions of extreme language delay is unknown. The sentence comprehension strategies of post-childhood, first-language (L1) learners of American Sign Language (ASL) with at least 9 years of language experience were investigated, in comparison to two control groups of learners with full access to language from birth (deaf native signers and hearing L2 learners who were native English speakers). The results of a sentence-to-picture matching experiment show that event knowledge overrides word order for post-childhood L1 learners, regardless of the animacy of the subject, while both deaf native signers and hearing L2 signers consistently rely on word order to comprehend sentences. Language inaccessibility throughout early childhood impedes the acquisition of even basic word order. Similar to the strategies used by very young children prior to the development of basic sentence structure, post-childhood L1 learners rely more on context and event knowledge to comprehend sentences. Language experience during childhood is critical to the development of basic sentence structure.
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http://dx.doi.org/10.1111/desc.13073DOI Listing
December 2020

Serotonin receptor 5-HT7 in Drosophila mushroom body neurons mediates larval appetitive olfactory learning.

Sci Rep 2020 12 4;10(1):21267. Epub 2020 Dec 4.

Neuroscience Program, Department of Biological Sciences, Ohio University, Athens, OH, USA.

Serotonin (5-HT) and dopamine are critical neuromodulators known to regulate a range of behaviors in invertebrates and mammals, such as learning and memory. Effects of both serotonin and dopamine are mediated largely through their downstream G-protein coupled receptors through cAMP-PKA signaling. While the role of dopamine in olfactory learning in Drosophila is well described, the function of serotonin and its downstream receptors on Drosophila olfactory learning remain largely unexplored. In this study we show that the output of serotonergic neurons, possibly through points of synaptic contacts on the mushroom body (MB), is essential for training during olfactory associative learning in Drosophila larvae. Additionally, we demonstrate that the regulation of olfactory associative learning by serotonin is mediated by its downstream receptor (d5-HT7) in a cAMP-dependent manner. We show that d5-HT7 expression specifically in the MB, an anatomical structure essential for olfactory learning in Drosophila, is critical for olfactory associative learning. Importantly our work shows that spatio-temporal restriction of d5-HT7 expression to the MB is sufficient to rescue olfactory learning deficits in a d5-HT7 null larvae. In summary, our results establish a critical, and previously unknown, role of d5-HT7 in olfactory learning.
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http://dx.doi.org/10.1038/s41598-020-77910-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718245PMC
December 2020

Comparison of the clinical effect of DHS and PFNA on senile osteoporotic fracture and their significance of changes in BALP expression level.

J Musculoskelet Neuronal Interact 2020 12;20(4):556-562

Department of Orthopedic Surgery, Affiliated Xuzhou Hospital of Jiangsu University, Xuzhou 3rd Hospital, Xuzhou, China.

Objective: To investigate the clinical effects of dynamic hip screw (DHS) and proximal femoral nail anti-rotation (PFNA) on senile osteoporosis patients and their effects on the expression level of bone-specific alkaline phosphatase (BALP).

Methods: 116 elderly patients with osteoporotic fracture were divided into DHS group (n=67) and PFNA group (n=49). BALP values were measured by ELISA before operation and 30 days after operation.

Results: The operation time, the bleeding volume, and the weight-bearing time of PFNA group was shorter than DHS group (p<0.05); the dominant blood loss and occult blood loss in PFNA group were less than those in DHS group (p<0.05); the healing time and detumescence time, the complications of PFNA group was fewer than the DHS group (p<0.05). The ten-meter walking speed and the five sitting tests in PFNA group were shorter than that in DHS group (p<0.05); the excellent and good rate and Harris score in PFNA group were higher than those in DHS group (p<0.05). The expression of BALP in PFNA group was lower than that in DHS group (p<0.05).

Conclusion: PFNA surgery has less trauma, fewer complications, more optimistic postoperative healing and recovery degree, and is more conducive to the reduction of BALP expression level.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716689PMC
December 2020

Fenugreek Cultivation with Emphasis on Historical Aspects and its uses in Traditional Medicine and Modern Pharmaceutical Science.

Mini Rev Med Chem 2021 ;21(6):724-730

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Fenugreek (Trigonella foenum-graecum L.) is a native plant found in the parts of Iran to the North of India, and is presently planted also in other regions of the world. Fenugreek is considered a notable multipurpose medicinal and traditional herb in Iran, India, and China for several centuries. The most important components of fenugreek seeds are protein, neutral detergent fiber, gum, lipids, moisture, ash and starch. Fenugreek seeds and leaves are anti-cholesterolemic, anti-tumor, antiinflammatory, carminative, demulcent, deobstruent, emollient, expectorant, galactogogue, febrifuge, laxative, hypoglycaemic, restorative, parasiticide and uterine tonic and useful in burning sensation. Traditionally, fenugreek seeds being used worldwide are beneficial for bone and muscles, respiratory system, gastro-intestinal system, female reproductive system, cardio-vascular system, endocrinology and hepatic. Fenugreek helps reduce cholesterol, reduce cardiovascular risk, control diabetes, a good consolation for sore throats, a remedy for acid reflux, constipation, colon cancer prevention, appropriate for kidney trouble, skin infection, increase milk production, reduce menstrual discomfort, and reduce menopause symptoms. It is also an appetite suppressant that helps in weight loss. Both modern science and traditional medicine integration with novel technologies and discoveries will secure the cultivation of medicinal herbs and promote sustainability in the long-term and a wide-range.
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http://dx.doi.org/10.2174/1389557520666201127104907DOI Listing
January 2021

Thromboresistance and endothelial healing in polymer-coated versus polymer-free drug-eluting stents: Implications for short-term dual anti-platelet therapy.

Int J Cardiol 2021 Mar 23;327:52-57. Epub 2020 Nov 23.

CVPath Institute, Gaithersburg, MD, United States of America; University of Maryland, Baltimore, MD, United States of America. Electronic address:

Background: Short-term dual antiplatelet therapy (DAPT) is a suitable strategy after stent implantation especially in patients at high risk for bleeding. The thromboresistant characteristics and the healing profile permanent polymer stents such as the Resolute Onyx- drug-eluting stent (DES) has never been tested against the current approved stents for short-term DAPT, the polymer free (PF) biolimus-eluting stent (PF-BES) and bare metal stents (BMS) in dedicated preclinical models.

Methods: An ex-vivo porcine arteriovenous shunt and in-vivo flow loop model were used to evaluate thromboresistance. The healing profile was assessed in the rabbit model at 28 days by confocal microscopy (CM), scanning electron microscopy (SEM) and histology. Onyx-DES was separately compared with Onyx-BMS in first experiment and PF-BES in second experiment.

Results: In an ex-vivo shunt model, CM and SEM showed significantly less platelet adhesion for Onyx-DES relative to Onyx-BMS and PF-BES. In a flow loop model using human blood, platelet adhesion was also significantly less in Onyx-DES as compared to PF-BES and Onyx-BMS. In the healing study, Onyx-BMS showed significantly greater healing profile relative to Onyx-DES as expected, whereas Onyx-DES showed equivalent endothelial coverage by SEM and significantly less Evan's blue uptake and comparable colocalization of p120 and vascular endothelial-cadherin when compared with PF-BES.

Conclusions: Onyx-DES showed qualities of thomboresistance and healing which appear to be compatible with short-term DAPT. Thromboresistance was superior to PF-BES and healing was equivalent to PF-BES in this pre-clinical study. Onyx-DES might provide advantages when considering short-term DAPT especially in patients at high risk of bleeding.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.030DOI Listing
March 2021

A novel injury site-natural antibody targeted complement inhibitor protects against lung transplant injury.

Am J Transplant 2020 Nov 19. Epub 2020 Nov 19.

Department of Microbiology and Immunology, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.

Complement is known to play a role in ischemia and reperfusion injury (IRI). A general paradigm is that complement is activated by self-reactive natural IgM antibodies (nAbs), after they engage postischemic neoepitopes. However, a role for nAbs in lung transplantation (LTx) has not been explored. Using mouse models of LTx, we investigated the role of two postischemic neoepitopes, modified annexin IV (B4) and a subset of phospholipids (C2), in LTx. Antibody deficient Rag1-/- recipient mice were protected from LTx IRI. Reconstitution with either B4 or C2nAb restored IRI, with C2 significantly more effective than B4 nAb. Based on these information, we developed/characterized a novel complement inhibitor composed of single-chain antibody (scFv) derived from the C2 nAb linked to Crry (C2scFv-Crry), a murine inhibitor of C3 activation. Using an allogeneic LTx, in which recipients contain a full nAb repertoire, C2scFv-Crry targeted to the LTx, inhibited IRI, and delayed acute rejection. Finally, we demonstrate the expression of the C2 neoepitope in human donor lungs, highlighting the translational potential of this approach.
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http://dx.doi.org/10.1111/ajt.16404DOI Listing
November 2020

Sumoylation of Human Parainfluenza Virus Type 3 Phosphoprotein Correlates with A Reduction in Viral Replication.

Virol Sin 2020 Nov 16. Epub 2020 Nov 16.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Human parainfluenza virus type 3 (HPIV3), a member of the Paramyxoviridae family, can cause lower respiratory disease in infants and young children. The phosphoprotein (P) of HPIV3 is an essential cofactor of the viral RNA-dependent RNA polymerase large protein (L). P connects nucleocapsid protein (N) with L to initiate genome transcription and replication. Sumoylation influences many important pathways of the target proteins, and many viral proteins are also themselves sumoylated. In this study, we found that the P of HPIV3 could be sumoylated, and mutation of K492 and K532 to arginine (P) failed to be sumoylated within P, which enhances HPIV3 minigenome activity. Biochemical studies showed that P had no effect on its interactions with N, formation of homo-tetramers and formation of inclusion bodies. Finally, we found that incorporation of K492R/K532R into a recombinant HPIV3 (rHPIV3-P) increased viral production in culture cells, suggesting that sumoylation attenuates functions of P and down-regulates viral replication.
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http://dx.doi.org/10.1007/s12250-020-00314-2DOI Listing
November 2020

Infliximab Therapy in Very Early Onset Crohn's Disease: Real-World Experience in China.

Dig Dis Sci 2020 Nov 16. Epub 2020 Nov 16.

Department of Gastroenterology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Data concerning of the effectiveness of infliximab in very early onset Crohn's disease patients are rare.

Aim: To assess the effectiveness and safety issues of infliximab treatment for this rare cohort.

Methods: The pediatric Crohn's disease activity index, Crohn's disease endoscopic index score, height, and weight were retrospectively recorded at baseline, week 14, and week 54. The rates of clinical remission and mucosal healing and growth of patients were compared between patients younger and older than 6 years of age. Loss of response or non-response to infliximab and adverse events were assessed during the entire treatment period.

Results: Sixty-five patients were enrolled in the study. Sixty-four percent and 40.0% of very early onset Crohn's disease patients achieved clinical remission and mucosal healing after induction therapy. Adjusted for the covariances, very early disease onset had no association with primary non-response (p = 0.360) or mucosal healing (p = 0.361). Early disease onset was associated with discontinuation of infliximab due to adverse events (hazard ratio [HR] 7.15, 95% CI 1.73-29.51, p = 0.006). Patients < 6 years had lower body mass index for age z score improvement during the induction phase (p = 0.04).

Conclusions: Very early onset Crohn's disease patients had similar non-response rates and mucosal healing rates as those who were 6 years or older during induction therapy. Greater discontinuation of infliximab due to adverse events was observed in very early onset Crohn's disease patients.
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http://dx.doi.org/10.1007/s10620-020-06699-0DOI Listing
November 2020

Mechanistic Studies of Nickel-Catalyzed Hydroarylation of Styrenes.

Org Lett 2020 Nov 4;22(22):8998-9003. Epub 2020 Nov 4.

Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, Tianjin University, Tianjin 300072, China.

The mechanism of nickel-catalyzed hydroarylation of styrenes has been explored with density functional theory. Instead of the stepwise pathway via a Ni(II)-H species, computational results unveil that the concerted RO-H oxidative addition/olefin insertion takes place kinetically favorable to generate the alkylnickel(II) species, which further undergoes transmetalation and reductive elimination to yield the hydroarylated product. The origins of regio- and stereoselectivity were revealed via analyzing the electronic and steric effects of the key transition states.
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http://dx.doi.org/10.1021/acs.orglett.0c03395DOI Listing
November 2020

Solitary hepatic lymphangioma mimicking liver malignancy: A case report and literature review.

World J Clin Cases 2020 Oct;8(19):4633-4643

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.

Background: Hepatic lymphangioma, a malformation of the liver lymphatic system, is a rare benign neoplasm and usually coexists with other visceral lymphangiomas. Solitary hepatic lymphangioma is much more rarely seen and could cause a clinical misinterpretation as malignancy.

Case Summary: A 50-year-old woman with a liver mass of approximately 3.5 cm was initially diagnosed with hepatocellular carcinoma given the risk factors for liver cancer that she presented with, including infection and jaundice, and also together with imaging results, which showed the mass enhanced quickly in the arterial phase and faded fast in the venous phase. The patient did not have the surgery first but received three rounds of transarterial chemoembolization because of her anxiety and fears for operation. Finally, the patient underwent laparoscopic liver segment 4b resection and cholecystectomy and was discharged from the hospital only 10 d after the operation. The pathological examination indicated the mass as hepatic lymphangioma. The patient has been followed up for 30 mo without recurrence. To raise the awareness of this misdiagnosed case and to better diagnose and treat this rare disease in future, we reviewed the published literature of solitary hepatic lymphangioma for its clinical symptoms, imaging presentation, operative techniques, histology features and prognosis.

Conclusion: Solitary hepatic lymphangioma mimicking malignancy makes diagnosis difficult. Complete surgical resection is the first choice to treat solitary hepatic lymphangioma.
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http://dx.doi.org/10.12998/wjcc.v8.i19.4633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559670PMC
October 2020

The roles of small-molecule inflammatory mediators in rheumatoid arthritis.

Scand J Immunol 2021 Mar 1;93(3):e12982. Epub 2020 Nov 1.

Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Although great progress has been made in the treatment of RA with antagonists of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1, the disease remains refractory in some patients. Previous studies have found that small-molecule inflammatory mediators, such as prostaglandins, leukotrienes, reactive oxygen species, nitric oxide, lipoxins and platelet-activating factor, play a significant role in the development of RA. Such compounds help to induce, maintain or reduce inflammation and could therefore be potential therapeutic targets. In this review, we describe the roles of various classes of small-molecule inflammatory mediators in RA and discuss the effects of some drugs that modulate their activity. Many drugs targeting these mediators have demonstrated good efficacy in mouse models of RA but not in patients. However, it is clear that many small-molecule inflammatory mediators play key roles in the pathogenesis of RA, and a better understanding of the underlying molecular pathways may assist in the development of targeted therapies that are efficacious in RA patients.
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http://dx.doi.org/10.1111/sji.12982DOI Listing
March 2021

FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway.

Front Cell Dev Biol 2020 31;8:843. Epub 2020 Aug 31.

Department of Obstetrics and Gynecology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

F-box proteins, as substrates for S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) ubiquitin ligase complexes, mediate the degradation of a large number of regulatory proteins involved in cancer processes. In this study, we found that F-box only protein 2 (FBXO2) was up-regulated in 21 endometrial carcinoma (EC) samples compared with five normal endometrium samples based on our Fudan cohort RNA-sequencing. The increased FBXO2 expression was associated with tumor stage, tumor grade, and histologic tumor type, and poor prognosis based on The Cancer Genome Atlas (TCGA) database. FBXO2 knockdown inhibited EC cell proliferation, and FBXO2 overexpression promoted the parental cell phenotype and . Fibrillin1 (FBN1) was also identified as a substrate for FBXO2 using a ubiquitination-proteome approach. In addition, promotion of EC proliferation by FBXO2 was regulated by specific proteins of the cell cycle (CDK4, CyclinD1, CyclinD2, and CyclinA1) and the autophagy signaling pathway (ATG4A and ATG4D) based on RNA sequencing (RNA-seq). We concluded that FBXO2 acts as an E3 ligase that targets FBN1 for ubiquitin-dependent degradation, so as to promote EC proliferation by regulating the cell cycle and the autophagy signaling pathway. Targeting FBXO2 may represent a potential therapeutic target for EC.
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http://dx.doi.org/10.3389/fcell.2020.00843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487413PMC
August 2020