Publications by authors named "Yuxin Zhou"

81 Publications

Effects of CDKN2B-AS1 on cellular proliferation, invasion and AKT3 expression are attenuated by miR-424-5p in a model of ovarian endometriosis.

Reprod Biomed Online 2021 Feb 12. Epub 2021 Feb 12.

Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha Hunan 410000, PR China. Electronic address:

Research Question: Endometriosis is a common and complicated gynaecologic disease. Long non-coding RNA CDKN2B-AS1 plays a crucial role in the development and progression of several cancers. Whether CDKN2B-AS1 contributes to endometriosis, however, remains unknown.

Design: Cellular proliferation, invasion and DNA synthesis abilities were assessed by CCK8, transwell and 5-ethynyle-2'-deoxyuridine assays. The expression of epithelial-mesenchymal transition markers and three isoforms of AKT was detected using Western blot. Real-time polymerase chain reaction was used to determine the relative expression levels of CDKN2B-AS1 and candidate miRNAs in ectopic, eutopic endometria and normal endometrial tissues. The relationship between CDKN2B-AS1 and miRNA was determined by luciferase reporter assays.

Results: The relative expression level of CDKN2B-AS1 was up-regulated in eutopic and ectopic endometria. In endometrial stromal cells and Ishikawa cells, CDKN2B-AS1 overexpression promoted cellular proliferation and invasion, and increased the protein expression of vimentin but decreased the expression of E-cadherin. miR-424-5p was confirmed the target of CDKN2B-AS1 through bioinformatics tools and luciferase reporter assays. In addition, the enhanced effect of cellular phenotype of CDKN2B-AS1 overexpression was significantly attenuated by miR-424-5p overexpression. Furthermore, miR-424-5p was able to directly target AKT3 through luciferase reporter assay. Mechanistically, CDKN2B-AS1 acts as a ceRNA by sponging miR-424-5p and targets AKT3.

Conclusions: The cellular mechanism of CDKN2B-AS1 in endometriosis was confirmed; CDKN2B-AS1 may be a potential target for ovarian endometriosis therapy.
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http://dx.doi.org/10.1016/j.rbmo.2021.02.004DOI Listing
February 2021

Molecular Mechanism of Secondary Endocrine Resistance in Luminal Breast Cancer.

Biomed Res Int 2021 16;2021:6618519. Epub 2021 Mar 16.

Li Huili Hospital, Ningbo Medical Center, Ningbo 315040, China.

Objective: The molecular mechanism of secondary resistance in Luminal breast cancer was studied to provide new ideas for the treatment of breast cancer.

Methods: The sensitivity of the downregulation of myeloid leukemia factor 1-interacting proteins (MLF1IP) to Tamoxifen (TAM) was tested by the Cell Counting Kit-8 (CCK-8). The apoptosis of MLF1IP-mediated resistance was analyzed by flow cytometry (FCM) with/without TAM. Western blot was used in detecting various kinds of apoptosis and the expression of the protein related to the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway to study the molecular mechanism of secondary endocrine resistance in Luminal breast cancer.

Results: The downregulation of MLF1IP could significantly increase the drug sensitivity of Michigan Cancer Foundation-7 (MCF-7) cells and also inhibit the proliferation of MCF-7 cells under the stimulation of drugs. Western blot results showed that the expression of Bcl-2-associated X (BAX), Caspase3, Caspase7, and Caspase9 proteins increased when MLF1IP was downregulated. The results of the PI3K/AKT signaling pathway revealed that the phosphatase and tensin homolog deleted on chromosome ten (PTEN) protein expression of MCF7-shRNA was higher than that of MCF7-NC cells, while the expression of p-AKT was lower than that of MCF7-NC cells.

Conclusions: (1) MLF1IP-related apoptosis resistance plays an essential role in MLF1IP-mediated secondary resistance of breast cancer cells. (2) MLF1IP promotes AKT phosphorylation by inhibiting the PTEN expression, thus activating the PI3K/AKT signaling pathway and causing the secondary resistance of Luminal breast cancer. (3) MLF1IP can be used as a factor to predict the endocrine resistance of Luminal breast cancer.
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http://dx.doi.org/10.1155/2021/6618519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990544PMC
March 2021

Simultaneous identification of Fritillariae cirrhosae bulbus and its common adulterants in one reaction by multiplex ligation-dependent probe amplification and high-resolution melting curve assay.

Gene 2021 Jun 29;785:145620. Epub 2021 Mar 29.

Hubei Institute for Drug Control, Wuhan 430012, China.

Fritillariae cirrhosae bulbus, a well-known and precious medicinal and edible herb in China, causes remarkable effects on swelling and relieving cough, with fewer side effects than other congeneric medicine. It has been subject to various cheaper congeneric adulteration because of its high price and limited production. In this paper, a rapid, high throughput, sensitive and efficient technique was described for simultaneous identification of F. cirrhosae bulbus and its common adulterants by employing multiplex ligation-dependent probe amplification coupled with high-resolution melting (MLPA-HRM) curve assay in their internal transcribed spacer 1 (ITS1) regions. This assay was highly sensitive with a detection limit of 0.19 ng genomic DNA, and highly specific with no cross-reaction with common adulterants. Mixed sample analysis showed as low as 10% adulteration can be detected from F. cirrhosae bulbus in one MLPA-HRM reaction. Overall, the method described in this paper is well suited for detecting adulteration in F. cirrhosae bulbus.
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http://dx.doi.org/10.1016/j.gene.2021.145620DOI Listing
June 2021

Dual PPARγ/ɑ agonist oroxyloside suppresses cell cycle progression by glycolipid metabolism switch-mediated increase of reactive oxygen species levels.

Free Radic Biol Med 2021 May 11;167:205-217. Epub 2021 Mar 11.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, PR China. Electronic address:

Cancer cells prefers to rely on aerobic glycolysis than pyruvate oxidation to meet the high demand of energy for rapidly proliferation. Peroxisome proliferator-activated receptors (PPARs) are a kind of important ligand-inducible transcription factors and play crucial roles in glucose and lipid metabolism. Careful designing of novel agonists for PPARs, may show improvement with the side effects and also increase the therapeutic value for cancer and other metabolic disorder diseases. Compared with normal human liver cells, lower expression or acitivity of PPARs is observed in hepatocellular carcinoma (HCC). In this study, we show that oroxyloside (OAG) is a new dual agonist of PPARγ/ɑ, and inhibits cell proliferation of HCC based on metabolic switch. Via both PPAR-dependent and PPAR-independent regulations on glycolipid metabolic enzymes, OAG shuts down the catabolism of glucose and promotes fatty acids oxidation to generate acetyl-CoA for TCA cycle and oxidative phosphorylation. The metabolic switch induced by OAG results in a marked increase of reactive oxygen species (ROS) levels, leading to rapid dephosphorylation of RB and cell-cycle arrest in G1 phase. Pyruvate dehydrogenase kinase 4 (PDK4) and β-Oxidation are required for the suppression of cell cycle progression by OAG. Together, our findings provide a new drug candidate and a viable therapeutic strategy for HCC based on metabolic reprogram.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.02.032DOI Listing
May 2021

The emerging role of long noncoding RNAs in esophageal carcinoma: from underlying mechanisms to clinical implications.

Cell Mol Life Sci 2021 Apr 19;78(7):3403-3422. Epub 2021 Jan 19.

Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.

Long noncoding RNAs (lncRNAs), a type of transcriptional product more than 200 nucleotides in length, have emerged as crucial regulators in human cancers. Accumulating data have recently indicated relationships between lncRNAs and esophageal carcinoma (EC). Of note, lncRNAs act as decoys/sponges, scaffolds, guides, and signals to regulate the expression of oncogenes or tumor suppressors at epigenetic, post-transcriptional, and protein levels, through which they exert their unique EC-driving or EC-suppressive functions. Moreover, the features of EC-related lncRNAs have been gradually exploited for developing novel diagnostic and therapeutic strategies in clinical scenarios. LncRNAs have the potential to be used as diagnostic and prognostic indicators individually or in combination with other clinical variables. Beyond these, although the time is not yet ripe, therapeutically targeting EC-related lncRNAs via gene editing, antisense oligonucleotides, RNA interference, and small molecules is likely one of the most promising therapeutic strategies for the next generation of cancer treatment. Herein, we focus on summarizing EC-driving/suppressive lncRNAs, as well as discussing their different features regarding expression profiles, modes of action, and oncological effects. Moreover, we further discuss current challenges and future developing possibilities of capitalizing on lncRNAs for EC early diagnosis and treatment.
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http://dx.doi.org/10.1007/s00018-020-03751-0DOI Listing
April 2021

The complete chloroplast genome of var. .

Mitochondrial DNA B Resour 2020 Jun 25;5(3):2547-2549. Epub 2020 Jun 25.

Wuhan Aimin Pharmaceutical Co., Ltd. R&D Center, Ezhou, Hubei, China.

In this study, we sequenced the complete chloroplast (cp) genome of Bunge var. (Rehder) Turland & N. H. Xia and compared it with cp genomes of congeneric species. The cp genome of var. is a circular molecule, 156,211 bp in length, with typical quadripartite structure. It has one large single copy (LSC) region of 85,211 bp and one small single copy (SSC) region of 18,124 bp that are separated by two inverted repeat regions (IR) of 26,438 bp. The cp genome encodes 133 genes comprising 85 protein-coding genes, 40 tRNA genes, and eight rRNA ribosomal genes. The overall GC content of the cp genome of var. is 37.93%. We conducted amaximum likelihood phylogenetic analysis, which revealed that var. is sister to and has a close relationship with L. (maples). We expect that the cp genome of var. will be useful for DNA barcoding and species delimitation for this species as well as future studies on the conservation, taxonomy, and evolutionary relationships of L.
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http://dx.doi.org/10.1080/23802359.2020.1780972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782131PMC
June 2020

Jisuikang Promotes the Repair of Spinal Cord Injury in Rats by Regulating NgR/RhoA/ROCK Signal Pathway.

Evid Based Complement Alternat Med 2020 28;2020:9542359. Epub 2020 Nov 28.

Department of Traumatology and Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Jisuikang (JSK) is an herbal formula composed of many kinds of traditional Chinese medicine, which has been proved to be effective in promoting the rehabilitation of patients with spinal cord injury (SCI) after more than ten years of clinical application. However, the mechanisms of JSK promoting nerve regeneration are yet to be clarified. The aim of this study was to investigate the effects of JSK protecting neurons, specifically the regulation of NgR/RhoA/ROCK signal pathway. The motor function of rats was evaluated by the BBB score and inclined plate test, Golgi staining and transmission electron microscope were used to observe the microstructure of nerve tissue, and fluorescence double-labeling method was used to detect neuronal apoptosis. In this study, we found that JSK could improve the motor function of rats with SCI, protect the microstructure (mitochondria, endoplasmic reticulum, and dendritic spine) of neurons, and reduce the apoptosis rate of neurons in rats with SCI. In addition, JSK could inhibit the expression of Nogo receptor (NgR) in neurons and the NgR/RhoA/ROCK signal pathway in rats with SCI. These results indicated JSK could improve the motor function of rats with SCI by inhibiting the NgR/RhoA/ROCK signal pathway, which suggests the potential applicability of JSK as a nerve regeneration agent.
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http://dx.doi.org/10.1155/2020/9542359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735860PMC
November 2020

Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys.

Exp Neurol 2021 Mar 29;337:113540. Epub 2020 Nov 29.

Department of Anatomy & Neurobiology, Boston University School of Medicine, United States; Center for Systems Neuroscience, Boston University, United States.

Cortical injury, such as stroke, causes neurotoxic cascades that lead to rapid death and/or damage to neurons and glia. Axonal and myelin damage in particular, are critical factors that lead to neuronal dysfunction and impair recovery of function after injury. These factors can be exacerbated in the aged brain where white matter damage is prevalent. Therapies that can ameliorate myelin damage and promote repair by targeting oligodendroglia, the cells that produce and maintain myelin, may facilitate recovery after injury, especially in the aged brain where these processes are already compromised. We previously reported that a novel therapeutic, Mesenchymal Stem Cell derived extracellular vesicles (MSC-EVs), administered intravenously at both 24 h and 14 days after cortical injury, reduced microgliosis (Go et al. 2019), reduced neuronal pathology (Medalla et al. 2020), and improved motor recovery (Moore et al. 2019) in aged female rhesus monkeys. Here, we evaluated the effect of MSC-EV treatment on changes in oligodendrocyte maturation and associated myelin markers in the sublesional white matter using immunohistochemistry, confocal microscopy, stereology, qRT-PCR, and ELISA. Compared to vehicle control monkeys, EV-treated monkeys showed a reduction in the density of damaged oligodendrocytes. Further, EV-treatment was associated with enhanced myelin maintenance, evidenced by upregulation of myelin-related genes and increases in actively myelinating oligodendrocytes in sublesional white matter. These changes in myelination correlate with the rate of motor recovery, suggesting that improved myelin maintenance facilitates this recovery. Overall, our results suggest that EVs act on oligodendrocytes to support myelination and improves functional recovery after injury in the aged brain. SIGNIFICANCE: We previously reported that EVs facilitate recovery of function after cortical injury in the aged monkey brain, while also reducing neuronal pathology (Medalla et al. 2020) and microgliosis (Go et al. 2019). However, the effect of injury and EVs on oligodendrocytes and myelination has not been characterized in the primate brain (Dewar et al. 1999; Sozmen et al. 2012; Zhang et al. 2013). In the present study, we assessed changes in myelination after cortical injury in aged monkeys. Our results show, for the first time, that MSC-EVs support recovery of function after cortical injury by enhancing myelin maintenance in the aged primate brain.
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http://dx.doi.org/10.1016/j.expneurol.2020.113540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946396PMC
March 2021

LINC01018 and SMIM25 sponged miR-182-5p in endometriosis revealed by the ceRNA network construction.

Int J Immunopathol Pharmacol 2020 Jan-Dec;34:2058738420976309

Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.

The current study intended to explore the interaction of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) under the background of competitive endogenous RNA (ceRNA) network in endometriosis (EMs). The differentially expressed miRNAs (DEmiRs), differentially expressed lncRNA (DELs), and differentially expressed genes (DEGs) between EMs ectopic (EC) and eutopic (EU) endometrium based on three RNA-sequencing datasets (GSE105765, GSE121406, and GSE105764) were identified, which were used for the construction of ceRNA network. Then, DEGs in the ceRNA network were performed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analysis. Besides, the DEmiRs in the ceRNA network were validated in GSE124010. And the target DELs and DEGs of verified DEmiRs were validated in GSE86534. The correlation of verified DEmiRs, DEGs, and DELs was explored. Moreover, gene set enrichment analysis (GSEA) was applied to investigate the function of verified DEmiRs, DEGs, and DELs. Overall, 1352 DEGs and 595 DELs from GSE105764, along with 27 overlapped DEmiRs between GSE105765 and GSE121406, were obtained. Subsequently, a ceRNA network, including 11 upregulated and 16 downregulated DEmiRs, 7 upregulated and 13 downregulated DELs, 48 upregulated and 46 downregulated DEGs, was constructed. The GO and KEGG pathway analysis showed that this ceRNA network probably was associated with inflammation-related pathways. Furthermore, hsa-miR-182-5p and its target DELs (LINC01018 and SMIM25) and DEGs (BNC2, CHL1, HMCN1, PRDM16) were successfully verified in the validation analysis. Besides, hsa-miR-182-5p was significantly negatively correlated with these target DELs and DEGs. The GSEA analysis implied that high expression of LINC01018, SMIM25, and CHL1, and low expression of hsa-miR-182-5p would activate inflammation-related pathways in endometriosis EU samples.LINC01018 and SMIM25 might sponge hsa-miR-182-5p to upregulate downstream genes such as CHL1 to promote the development of endometriosis.
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http://dx.doi.org/10.1177/2058738420976309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691905PMC
November 2020

Glycolysis inhibition and apoptosis induction in human prostate cancer cells by FV-429-mediated regulation of AR-AKT-HK2 signaling network.

Food Chem Toxicol 2020 Sep 30;143:111517. Epub 2020 Jun 30.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China. Electronic address:

Prostate cancer (PCa) depends on androgen receptor (AR) signaling to regulate cell metabolism, including glycolysis, and thereby promotes tumor growth. Glycolysis is overactive in PCa and associated with poor prognosis, but the therapeutic efficacy of glycolysis inhibitors has thus far been limited by their inability to induce cell death. FV-429, a flavonoid derivative of Wogonin, is a glycolysis inhibitor that has shown anti-cancer promise. In this study, we used FV-429 as an anti-PCa agent and investigated its mechanisms of action. In vitro, both the glycolytic ability and the viability of PCa cells were inhibited by FV-429. We found that FV-429 could induce mitochondrial dysfunction and apoptosis, with AKT-HK2 signaling pathway playing a key role. In addition, FV-429 had a pro-apoptotic effect on human prostate cancer cells that relied on the inhibition of AR expression and activity. In vivo, FV-429 exerted significant tumor-repressing activity with high safety in the xenograft model using LNCaP cells. In summary, we demonstrated that FV-429 induced glycolysis inhibition and apoptosis in human prostate cancer cells by downregulating the AR-AKT-HK2 signaling network, making FV-429 a promising candidate as one therapeutic agent for advanced PCa.
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http://dx.doi.org/10.1016/j.fct.2020.111517DOI Listing
September 2020

Oroxylin A suppresses ACTN1 expression to inactivate cancer-associated fibroblasts and restrain breast cancer metastasis.

Pharmacol Res 2020 09 31;159:104981. Epub 2020 May 31.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China. Electronic address:

Tumor initiation and progression are not only ascribed to the behavior of cancer cells, but also profoundly influenced by the tumor microenvironment. Inside, cancer-associated fibroblasts (CAFs) have become key factors to accelerate growth and metastasis for the abundance in most solid tumors. Our group previously reported that Oroxylin A (OA), a flavone from Scutellaria Baicalensis Georgi, possess the ability to suppress growth and invasion of several tumor cells. However, the regulatory effect of OA on stromal microenvironment is poorly understood. In this study, breast cancer-induced fibroblasts and primary breast CAFs from MMTV-PyMT mice were used to evaluate the influence of OA on the activation of fibroblasts. Results showed that OA could decrease the expression of α-SMA, fibronectin, vimentin and matrix metalloproteinases (MMPs). Thus, OA-deactivated CAFs did not further promote the proliferation and invasion in breast cancer cells. In vivo experiments, OA could also impede tumor metastasis through exhausting progressive CAFs. Mechanically, OA could specifically bind ACTN1 and significantly inhibit its expression to prevent CAF activation. As a consequence, OA could decrease the phosphorylation of FAK and STAT3, and reduce the secretion of CCL2 in CAFs. Altogether, OA could remodel stromal microenvironment and it is a potential therapeutic agent in breast cancer.
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http://dx.doi.org/10.1016/j.phrs.2020.104981DOI Listing
September 2020

A meta-analysis on the prevalence, associated factors and diagnostic methods of mental stress induced myocardial ischemia.

J Transl Med 2020 05 29;18(1):218. Epub 2020 May 29.

Cardiology Department, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.

Background: The high prevalence of mental stress induced myocardial ischemia (MSIMI) causes double risk of adverse cardiac events in patients with MSIMI. However, multiple types of mental stress, diagnostic techniques, and diagnostic measurements may increase the complexity and heterogeneity in the assessment of MSIMI. Therefore, we performed this meta-analysis to assess the prevalence, associated factors, and diagnostic methods of MSIMI.

Methods: We systematically searched PubMed, EMBACE, Web of Science, CNKI, Wanfang through 1 Feb 2020 in English and Chinese. Review Manager (RevMan) Version 5.3 and Stata 12.0 were used for data analyses.

Results: Twenty articles were enrolled. The pooled estimates for the prevalence of MSIMI in CAD patients was 32%. Potential associated factors of MSIMI involved history of post myocardial infarction (MI), or coronary artery bypass graft (CABG) (RR: 1.29, 95% CI 1.00-1.66, P = 0.05; RR: 1.59, 95% CI 1.00-2.52, P = 0.05). Evidence supported that diagnostic methods could influence the prevalence of MSIMI. Significant differences of MSIMI prevalence were found in different types of mental stress (Public Speaking: 22%; Mental arithmetic: 26%; Anger recall: 34%; Two types: 37%; Three or more than three types: 43%, P = 0.02), diagnostic techniques (SPECT: 26%; RNV: 38%; ECG: 16%; Echocardiography: 41%; Two types: 43%, P < 0.0001), and diagnostic measurements (LVEF decrease: 19%; WMA: 51%; ST depression: 16%; MPD: 26%; Two or more than two measurements: 45%, P < 0.00001). Moreover, univariate meta-regression demonstrated that MSIMI was linked with mental stress (exp(b): 1.0508, SE: 0.0201, P: 0.018).

Conclusions: This meta-analysis implicated that patients with diabetes, post MI or CABG might be more vulnerable to MSIMI. However, the prevalence of MSIMI could be influenced by diagnostic methods, especially the adopted types of mental stress, diagnostic techniques and measurements. Therefore, it is necessary to formulate a standard diagnostic method for MSIMI, which should be adequate, assessable, and affordable worldwide. Registration PROSPERO. Online Protocol: CRD42020162822.
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http://dx.doi.org/10.1186/s12967-020-02383-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257246PMC
May 2020

Multiplex Ligation-Dependent Probe Amplification for Simultaneous Identification of and Its Common Adulterants in a Single Assay.

Front Pharmacol 2020 21;11:501. Epub 2020 Apr 21.

Chinese Medicine Testing and Research Center, Hubei Institute for Drug Control, Wuhan, China.

, an important traditional Chinese medicine, possesses remarkable medicinal activities, while lots of adulterants from other species were misused as for its large demand and resource starvation. In order to accurately identify and its common adulterants such as , , , and , a simultaneous identification method was designed with multiplex ligation-dependent probe amplification (MLPA) analysis. Five species-specific MLPA probe-couples for and its common adulterants were designed based on the universal primer amplified sequences, which can specifically detect the five species with no mutual interference, and sensitivity analysis showed as less as 5% or 8.75% adulterants in the mixed samples can be identified in a MLPA assay, especially, the relative quantity of the adulterants can be also inferred based on the MLPA peak area values. Moreover, the results of the present study confirmed the effectiveness of this technique in terms of simultaneous identification of and its common adulterants in an assay, which has great potential for ensuring the safety of this commercially valuable snake species.
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http://dx.doi.org/10.3389/fphar.2020.00501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186403PMC
April 2020

Genome of the webworm Hyphantria cunea unveils genetic adaptations supporting its rapid invasion and spread.

BMC Genomics 2020 Mar 18;21(1):242. Epub 2020 Mar 18.

Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, Jilin, China.

Background: The fall webworm Hyphantria cunea is an invasive and polyphagous defoliator pest that feeds on nearly any type of deciduous tree worldwide. The silk web of H. cunea aids its aggregating behavior, provides thermal regulation and is regarded as one of causes for its rapid spread. In addition, both chemosensory and detoxification genes are vital for host adaptation in insects.

Results: Here, a high-quality genome of H. cunea was obtained. Silk-web-related genes were identified from the genome, and successful silencing of the silk protein gene HcunFib-H resulted in a significant decrease in silk web shelter production. The CAFE analysis showed that some chemosensory and detoxification gene families, such as CSPs, CCEs, GSTs and UGTs, were expanded. A transcriptome analysis using the newly sequenced H. cunea genome showed that most chemosensory genes were specifically expressed in the antennae, while most detoxification genes were highly expressed during the feeding peak. Moreover, we found that many nutrient-related genes and one detoxification gene, HcunP450 (CYP306A1), were under significant positive selection, suggesting a crucial role of these genes in host adaptation in H. cunea. At the metagenomic level, several microbial communities in H. cunea gut and their metabolic pathways might be beneficial to H. cunea for nutrient metabolism and detoxification, and might also contribute to its host adaptation.

Conclusions: These findings explain the host and environmental adaptations of H. cunea at the genetic level and provide partial evidence for the cause of its rapid invasion and potential gene targets for innovative pest management strategies.
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http://dx.doi.org/10.1186/s12864-020-6629-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079503PMC
March 2020

Structural basis of Fusarium myosin I inhibition by phenamacril.

PLoS Pathog 2020 03 12;16(3):e1008323. Epub 2020 Mar 12.

Key Laboratory of Pesticide, College of Plant Protection, Nanjing Agricultural University, Nanjing, China.

Fusarium is a genus of filamentous fungi that includes species that cause devastating diseases in major staple crops, such as wheat, maize, rice, and barley, resulting in severe yield losses and mycotoxin contamination of infected grains. Phenamacril is a novel fungicide that is considered environmentally benign due to its exceptional specificity; it inhibits the ATPase activity of the sole class I myosin of only a subset of Fusarium species including the major plant pathogens F. graminearum, F. asiaticum and F. fujikuroi. To understand the underlying mechanisms of inhibition, species specificity, and resistance mutations, we have determined the crystal structure of phenamacril-bound F. graminearum myosin I. Phenamacril binds in the actin-binding cleft in a new allosteric pocket that contains the central residue of the regulatory Switch 2 loop and that is collapsed in the structure of a myosin with closed actin-binding cleft, suggesting that pocket occupancy blocks cleft closure. We have further identified a single, transferable phenamacril-binding residue found exclusively in phenamacril-sensitive myosins to confer phenamacril selectivity.
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http://dx.doi.org/10.1371/journal.ppat.1008323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100991PMC
March 2020

Diverged morphology changes of astrocytic and neuronal primary cilia under reactive insults.

Mol Brain 2020 03 2;13(1):28. Epub 2020 Mar 2.

Department of Molecular, Cellular and Biomedical Sciences, College of Life Sciences and Agriculture, University of New Hampshire, 389 Rudman Hall, 46 College Road, Durham, NH, 03824, USA.

Primary cilia are centriole-derived sensory organelles that are present in most mammalian cells, including astrocytes and neurons. Evidence is emerging that astrocyte and neuronal primary cilia demonstrate a dichotomy in the mature mouse brain. However, it is unknown how astrocytic and neuronal primary cilia change their morphology and ciliary proteins when exposed to reactive insults including epilepsy and traumatic brain injury. We used a double transgenic mouse strain (Arl13b-mCherry; Centrin2-GFP), in which we found spontaneous seizures, and a cortical injury model to examine the morphological changes of astrocytic and neuronal primary cilia under reactive conditions. Transgenic overexpression of Arl13b drastically increases the length of astrocytic and neuronal primary cilia in the hippocampus, as well as the cilia lengths of cultured astrocytes and neurons. Spontaneous seizures shorten Arl13b-positive astrocytic cilia and AC3-positive neuronal cilia in the hippocampus. In a cortical injury model, Arl13b is not detectable in primary cilia, but Arl13b protein relocates to the cell body and has robust expression in the proximity of injured tissues. In contrast, the number of AC3-positive cilia near injured tissues remains unchanged, but their lengths become shorter. These results on astrocytic cilia implicate Arl13b in regulating astrocyte proliferation and tissue regeneration, while the shortening of AC3-positive cilia suggests adaptive changes of neuronal primary cilia under excitotoxicity.
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http://dx.doi.org/10.1186/s13041-020-00571-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053156PMC
March 2020

Correction: Wogonin induces cell cycle arrest and erythroid differentiation in imatinib-resistant K562 cells and primary CML cells.

Oncotarget 2020 Jan 21;11(3):300-301. Epub 2020 Jan 21.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People's Republic of China.

[This corrects the article DOI: 10.18632/oncotarget.2340.].
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http://dx.doi.org/10.18632/oncotarget.27373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980629PMC
January 2020

Induction of activity synchronization among primed hippocampal neurons out of random dynamics is key for trace memory formation and retrieval.

FASEB J 2020 03 15;34(3):3658-3676. Epub 2020 Jan 15.

Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH, USA.

Memory is thought to be encoded by sparsely distributed neuronal ensembles in memory-related regions. However, it is unclear how memory-eligible neurons react during learning to encode trace fear memory and how they retrieve a memory. We implemented a fiber-optic confocal fluorescence endomicroscope to directly visualize calcium dynamics of hippocampal CA1 neurons in freely behaving mice subjected to trace fear conditioning. Here we report that the overall activity levels of CA1 neurons showed a right-skewed lognormal distribution, with a small portion of highly active neurons (termed Primed Neurons) filling the long-tail. Repetitive training induced Primed Neurons to shift from random activity to well-tuned synchronization. The emergence of activity synchronization coincided with the appearance of mouse freezing behaviors. In recall, a partial synchronization among the same subset of Primed Neurons was induced from random dynamics, which also coincided with mouse freezing behaviors. Additionally, training-induced synchronization facilitated robust calcium entry into Primed Neurons. In contrast, most CA1 neurons did not respond to tone and foot shock throughout the training and recall cycles. In conclusion, Primed Neurons are preferably recruited to encode trace fear memory and induction of activity synchronization among Primed Neurons out of random dynamics is critical for trace memory formation and retrieval.
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http://dx.doi.org/10.1096/fj.201902274RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079015PMC
March 2020

Dynamic Extreme Aneuploidy (DEA) in the vegetable pathogen Phytophthora capsici and the potential for rapid asexual evolution.

PLoS One 2020 7;15(1):e0227250. Epub 2020 Jan 7.

Department of Entomology and Plant Pathology, The University of Tennessee, Knoxville, Tennessee, United States of America.

Oomycete plant pathogens are difficult to control and routine genetic research is challenging. A major problem is instability of isolates. Here we characterize >600 field and single zoospore isolates of Phytophthora capsici for inheritance of mating type, sensitivity to mefenoxam, chromosome copy number and heterozygous allele frequencies. The A2 mating type was highly unstable with 26% of 241 A2 isolates remaining A2. The A1 mating type was stable. Isolates intermediately resistant to mefenoxam produced fully resistant single-spore progeny. Sensitive isolates remained fully sensitive. Genome re-sequencing of single zoospore isolates revealed extreme aneuploidy; a phenomenon dubbed Dynamic Extreme Aneuploidy (DEA). DEA is characterized by the asexual inheritance of diverse intra-genomic combinations of chromosomal ploidy ranging from 2N to 3N and heterozygous allele frequencies that do not strictly correspond to ploidy. Isolates sectoring on agar media showed dramatically altered heterozygous allele frequencies. DEA can explain the rapid increase of advantageous alleles (e.g. drug resistance), mating type switches and copy neutral loss of heterozygosity (LOH). Although the mechanisms driving DEA are unknown, it can play an important role in adaptation and evolution and seriously hinders all aspects of P. capsici research.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227250PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946123PMC
April 2020

Correction to: Oroxylin A promotes PTEN-mediated negative regulation of MDM2 transcription via SIRT3-mediated deacetylation to stabilize p53 and inhibit glycolysis in wt-p53 cancer cells.

J Hematol Oncol 2019 Dec 30;12(1):143. Epub 2019 Dec 30.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.

The original article [1] contains several errors.
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http://dx.doi.org/10.1186/s13045-019-0792-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936048PMC
December 2019

Correction to: Artemisinin derivatives inactivate cancer-associated fibroblasts through suppressing TGF-β signaling in breast cancer.

J Exp Clin Cancer Res 2019 11 5;38(1):451. Epub 2019 Nov 5.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.

In the original publication of this article [1], Fig. 3 is wrong, but does not affect discussions and conclusions drawn in the article.
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http://dx.doi.org/10.1186/s13046-019-1441-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829918PMC
November 2019

Corrigendum to "Selective anti-tumor activity of wogonin targeting the Warburg effect through stablizing p53" [Pharmacol. Res. 135 (2018) 49-59].

Pharmacol Res 2019 Dec 31;150:104498. Epub 2019 Oct 31.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China; Department of Basic Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.phrs.2019.104498DOI Listing
December 2019

Flavonoid GL-V9 induces apoptosis and inhibits glycolysis of breast cancer via disrupting GSK-3β-modulated mitochondrial binding of HKII.

Free Radic Biol Med 2020 01 24;146:119-129. Epub 2019 Oct 24.

Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA. Electronic address:

Energy metabolism plays important roles in the growth and survival of cancer cells. Here, we find a newly synthesized flavonoid named GL-V9, which inhibits glycolysis and induces apoptosis of human breast cancer cell lines, and investigate the underlying mechanism. Results show that hexokinase II (HKII) plays important roles in the anticancer effects of GL-V9. GL-V9 not only downregulates the expression of HKII in MDA-MB-231 and MCF-7 cells, but also induces dissociation of HKII from voltage-dependent anion channel (VDAC) in mitochondria, resulting in glycolytic inhibition and mitochondrial-mediated apoptosis. The dissociation of mitochondrial HKII is attributed to GSK-3β-induced phosphorylation of mitochondrial VDAC. Our in vivo experiments also show that GL-V9 significantly inhibits the growth of human breast cancer due to activation of GSK-3β and inactivation of AKT. Thus, GL-V9 induces cytotoxicity in breast cancer cells via disrupting the mitochondrial binding of HKII. Our works demonstrate the significance of metabolic regulators in cancer growth and offer a fresh insight into the molecular basis for the development of GL-V9 as a candidate for breast carcinoma treatment.
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http://dx.doi.org/10.1016/j.freeradbiomed.2019.10.413DOI Listing
January 2020

Corrigendum to "HQS-3, a newly synthesized flavonoid, possesses potent anti-tumor effect in vivo and in vitro" [European Journal of Pharmaceutical Science (2013) 649-658].

Eur J Pharm Sci 2019 12 18;140:105074. Epub 2019 Oct 18.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.ejps.2019.105074DOI Listing
December 2019

Corrigendum to "Wogonin inhibits tumor angiogenesis via degradation of HIF-1α protein" [Toxicology and Applied Pharmacology 271 (2013) 144-145].

Toxicol Appl Pharmacol 2019 Dec 14;384:114762. Epub 2019 Sep 14.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210,009, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.taap.2019.114762DOI Listing
December 2019

LZ-101, a novel derivative of danofloxacin, induces mitochondrial apoptosis by stabilizing FOXO3a via blocking autophagy flux in NSCLC cells.

Cell Death Dis 2019 06 19;10(7):484. Epub 2019 Jun 19.

Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA.

Non-small-cell lung carcinoma (NSCLC) continues to be a vital disease worldwide for its high incidence and consequent mortality rate. In this study, we investigated the anti-cancer effect of LZ-101, a new derivative of danofloxacin, against non-small-cell lung cancer and the underlying mechanisms. In vitro, LZ-101 inhibited the viability of human non-small cell lung cancer cell lines. We demonstrated that LZ-101 induced mitochondrial-mediated apoptosis by increasing Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (ΔΨm), release of cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) in A549 cells. Further research illuminated that LZ-101 induced apoptosis was related to the activation of FOXO3a/Bim pathway. Moreover, we found that LZ-101 increased the stability of FOXO3a by blocking autophagy-dependent FOXO3a degradation. However, inhibition of autophagosome formation abolished FOXO3a stabilization and apoptosis induced by LZ-101. In vivo, LZ-101 exerted a remarkable anti-tumor activity with high safety in xenograft model inoculated A549 tumor through the same mechanism as in our in vitro study. In conclusion, our findings indicated that LZ-101 induces mitochondrial apoptosis and stabilizes FOXO3a by blocking autophagy flux.
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http://dx.doi.org/10.1038/s41419-019-1714-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584698PMC
June 2019

Resistance risk assessment for fludioxonil in Sclerotinia homoeocarpa in China.

Pestic Biochem Physiol 2019 May 12;156:123-128. Epub 2019 Feb 12.

Department of Plant Pathology, China Agricultural University, Beijing 100193, PR China.

Sclerotinia homoeocarpa causes dollar spot disease on turfgrass and is a serious problem on many species worldwide. Fludioxonil, a phenylpyrrole fungicide, is not currently registered for dollar spot control in China. In this study, the baseline sensitivity to fludioxonil was established using an in vitro assay for 105 isolates of S. homoeocarpa collected from 10 locations in different regions of China. Results indicate that the frequency distribution of effective concentration for 50% inhibition of mycelial growth (EC) values of the S. homoeocarpa isolates was unimodal (W = 0.9847, P = .2730). The mean EC value was 0.0020 ± 0.0006 μg/ml with a range from 0.0003 to 0.0035 μg/ml. A total of 7 fludioxonil-resistant mutants were obtained in laboratory, the mutants were stable in fludioxonil sensitivity after the 10th transfer, with resistance factor (RF) ranging from 4.320 to >13,901.4. The mutants showed a positive cross-resistance between fludioxonil and the dicarboximide fungicide iprodione, but not propiconazole, fluazinam, and thiophanate-methyl. When mycelial growth rate, pathogenicity and osmotic sensitivity were assessed, the mutants decreased in the fitness compared with their parental isolates. Sequence alignment of the histidine kinase gene Shos1 revealed a 13-bp fragment deletion only in one mutant, no mutations were observed on Shos1 in the rest resistant mutants.
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http://dx.doi.org/10.1016/j.pestbp.2019.02.011DOI Listing
May 2019

Repetitive transcranial magnetic stimulation protects mice against 6-OHDA-induced Parkinson's disease symptoms by regulating brain amyloid β level.

Mol Cell Biochem 2019 Aug 19;458(1-2):71-78. Epub 2019 Apr 19.

Department of Rehabilitation, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.

Repetitive transcranial magnetic stimulation (rTMS) is a technique protecting neurons against diverse neurodegenerative disorders by delivering magnetic stimuli into the brain through the intact scalp. In the current study, the protection effect of rTMS on Parkinson's disease (PD) and the associated mechanism driving the treatment were explored. The PD symptoms were induced using 6-OHDA in mice, and the effect of rTMS of two frequencies (1 Hz and 10 Hz) on the cognitive behaviors and neuron viability was detected. Afterwards, the level of Aβ and activity of MKK7-ERK-Fos-APP axis under the administration of rTMS were recorded as well. The intracranial injection of 6-OHDA impaired the cognitive behaviors of the mice in the test of Morris water maze as well as reducing the viability and number of neurons in PD mice. After the treatment of rTMS of both frequencies, the cognitive function of mice was improved and the neuron viability and number were restored in mice brain tissues. The administration of rTMS also increased the cerebrospinal fluid (CSF) level of Aβ in PD mice, which was accompanied by the suppressed levels of p-MKK7, p-ERK1/2, p-c-Fos, and APP. Moreover, the effect of rTMS on mice nerve system was all exerted in a frequency-dependent manner. In conclusion, the findings outlined in the current study affirmed the protection effect of rTMS against PD. The anti-PD function of rTMS was associated with the suppression of MKK7-ERK-Fos-APP axis, which subsequently resulted in the increased CSF Aβ level and decreased brain Aβ level.
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http://dx.doi.org/10.1007/s11010-019-03531-wDOI Listing
August 2019

Association between miscellaneous symptoms and primary symptom dimensions among chinese adults with obsessive-compulsive disorder.

Psychiatry Res 2019 04 19;274:274-279. Epub 2019 Feb 19.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai, 200030, China. Electronic address:

Obsessive compulsive-disorder (OCD) is a common mental illness characterized by the presence of obsessions and/or compulsions. Symptom presence and severity is typically evaluated through the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). However, miscellaneous symptoms embedded within the Y-BOCS Symptom Checklist have often been overlooked despite being associated with certain dimensions. In this study, we used exploratory factor analysis and logistic regression to explore the relationship between various miscellaneous symptoms and OCD symptom dimensions among 123 Chinese adults with OCD. A four-dimensional model was factorially derived: Obsessions, Symmetry/Ritual, Contamination/Cleaning and Contamination/Cleaning. In general, 11 out of 17 miscellaneous symptoms were associated with one or more of the symptom dimensions. Among them, the Obsessions dimension was significantly associated with seven miscellaneous symptoms: "Fear of not saying just the right thing," "Intrusive (non-violent) images," "Intrusive nonsense sounds, words", etc. The Symmetry/Ritual dimension was significantly associated with "Need to tell, ask, or confess." The Contamination/Cleaning dimension was related to "Need to know or remember". The Hoarding/Religion dimension was related to "Fear of losing things," and "Superstitious fears". Results contribute to the clinical assessment, diagnosis and treatment of Chinese patients with OCD by understanding the extent to which certain miscellaneous symptoms are associated with primary symptom dimensions.
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http://dx.doi.org/10.1016/j.psychres.2019.02.042DOI Listing
April 2019

Comparative Phosphoproteomic Profiling of Type III Adenylyl Cyclase Knockout and Control, Male, and Female Mice.

Front Cell Neurosci 2019 13;13:34. Epub 2019 Feb 13.

Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH, United States.

Type III adenylyl cyclase (AC3, ) is predominantly enriched in neuronal primary cilia throughout the central nervous system (CNS). Genome-wide association studies in humans have associated with major depressive disorder and autistic spectrum disorder, both of which exhibit sexual dimorphism. To date, it is unclear how AC3 affects protein phosphorylation and signal networks in central neurons, and what causes the sexual dimorphism of autism. We employed a mass spectrometry (MS)-based phosphoproteomic approach to quantitatively profile differences in phosphorylation between inducible AC3 knockout (KO) and wild type (WT), male and female mice. In total, we identified 4,655 phosphopeptides from 1,756 proteins, among which 565 phosphopeptides from 322 proteins were repetitively detected in all samples. Over 46% phosphopeptides were identified in at least three out of eight biological replicas. Comparison of AC3 KO and WT datasets revealed that phosphopeptides with motifs matching proline-directed kinases' recognition sites had a lower abundance in the KO dataset than in WTs. We detected 14 phosphopeptides restricted to WT dataset (i.e., ) and 35 exclusively in KOs (i.e., ). Moreover, 95 phosphopeptides (out of 90 proteins) were identified only in female dataset and 26 only in males. Label-free MS spectrum quantification using Skyline further identified phosphopeptides that had higher abundance in each sample group. In total, 204 proteins had sex-biased phosphorylation and 167 of them had increased expression in females relative to males. Interestingly, among the 204 gender-biased phosphoproteins, 31% were found to be associated with autism, including . Therefore, this study also provides the first phosphoproteomics evidence suggesting that gender-biased post-translational phosphorylation may be implicated in the sexual dimorphism of autism.
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http://dx.doi.org/10.3389/fncel.2019.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381875PMC
February 2019