Publications by authors named "Yanhui Liu"

306 Publications

Calcineurin Immune Signaling in Response to Zinc Challenge in the Naked Carp Gymnocypris eckloni.

Bull Environ Contam Toxicol 2021 May 23;106(5):792-798. Epub 2021 Mar 23.

College of Eco-Environmental Engineering, Qinghai University, Xining, 810016, China.

Zinc pollution impairs neural processes and protein function and also effects calcium-related transcriptional regulation and enzyme activity. In this study, we investigated pathways that potentially respond to calcium signaling under Zn stress. Specifically we measured relative expressions of GeCNAα, GeCNB, GeMT, GeTNF-α, GeIL-1β, and GeHsp90 in gills, livers, and kidneys of the indicator species Gymnocypris eckloni and found wide variation in their expression between tissues during the course of Zn exposure. Notably, GeCNAα, GeCNB, GeTNF-α, GeIL-1β, and GeMT were rapidly and strongly up-regulated in gills; GeIL-1β and GeHsp90 transcription was quickly induced in kidneys; and GeCNB, GeTNF-α, GeIL-1β, and GeHsp90 were most rapidly up-regulated in livers. GeCNAα and GeMT showed a contrasting late transcriptional up-regulation. These results suggest independent branches for chelation and immune responses during self-protection against Zn toxicity, and the immune response appears to be faster than metal chelation.
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http://dx.doi.org/10.1007/s00128-021-03178-8DOI Listing
May 2021

Role of organic anion transporter 3 in the renal excretion of biapenem and potential drug-drug interactions.

Eur J Pharm Sci 2021 Mar 19;162:105814. Epub 2021 Mar 19.

Department of Pharmacy, Shanghai Pudong New Area Gongli Hospital, The Second Military Medical University, 219 Miaopu Road, Shanghai 200135, PR China. Electronic address:

Biapenem is a carbapenem antibiotic. It is excreted predominantly through the kidney as unchanged forms. However, the molecular mechanism of renal excretion of biapenem and potential drug-drug interactions (DDIs) were still unknown. In the present study, the role of organic anion transporters (OAT) 1/3 and organic cation transporters (OCT) 2 in the renal excretion of biapenem, and the potential DDIs between biapenem and six clinical commonly prescribed antibiotics and antiviral drugs that acted as substrates or inhibitors of OAT3 were evaluated in vitro. Further, the effect of probenecid on the pharmacokinetics of biapenem was explored in the rats. We observed that biapenem could not inhibit the transport activities of OAT1 or OCT2, while mildly inhibited OAT3 (IC >500 μM). Among the tested antibiotics and antiviral drugs, the relatively high DDI index values (maximal unbound plasma concentration over IC, I/IC) were found for piperacillin, linezolid and benzylpenicillin, which were 2.84, 1.7 and 0.62, respectively. Although probenecid had the highest DDI index (27.1) in vitro, no significant impact of it on the pharmacokinetics of biapenem was observed in the rats. Our results indicated that biapenem was primarily eliminated by the glomerular filtration, while OAT3-mediated renal tubular secretion was a minor route. Biapenem is not a clinically relevant substrate or inhibitor because of its low affinity to OAT3. According to current results, it would be safe to use biapenem with other antibiotics and antiviral drugs that acted as substrates or inhibitors of OAT3.
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http://dx.doi.org/10.1016/j.ejps.2021.105814DOI Listing
March 2021

A composite single-nucleotide polymorphism prediction signature for extranodal natural killer/T-cell lymphoma.

Blood 2021 Mar 16. Epub 2021 Mar 16.

Sun Yat-Sen University Cancer Center, Guangzhou, China.

Current prognostic scoring systems based on clinicopathologic variables are inadequate in predicting the survival and treatment response of extranodal natural killer/T-cell lymphoma (ENKTL) patients undergoing non-anthracyline-based treatment. We aimed to construct a classifier based on single-nucleotide polymorphisms (SNPs) for improving predictive accuracy and guiding clinical decision-making. The data of 722 patients with ENKTL from international multicenters were analyzed. A 7-SNP-based classifier was constructed using LASSO Cox regression in the training cohort (n=336) and further validated in the internal testing (n=144) and two external validation cohorts (n=142; n=100). The 7-SNP-based classifier showed good prognostic predictive efficacy in the training cohort and the three validation cohorts. Patients with high and low risk scores calculated by the classifier exhibited significantly different progression-free survival (PFS) and overall survival (OS) (all p<0.001). The 7-SNP-based classifier was further proved to be an independent prognostic factor by multivariate analysis, and its predictive accuracy was significantly better than clinicopathological risk variables. The application of the 7-SNP-based classifier was not affected by sample types. Notably, chemotherapy combined with radiotherapy significnalty improved PFS and OS versus radiotherapy alone in high risk Ann Anbor stage I patients, while there was no statistical difference between the two therapeutic modalities among low risk patients. A nomogram was constructed comprised of the classifier and clinicopathological variables, and showed remarkably better predictive accuracy than that of each variable alone. The 7-SNP-based classifier is a complement to existing risk stratification systems in ENKTL, which could have significant implications for clinical decision-making for ENKTL patients.
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http://dx.doi.org/10.1182/blood.2020010637DOI Listing
March 2021

Rheb mediates neuronal-activity-induced mitochondrial energetics through mTORC1-independent PDH activation.

Dev Cell 2021 Mar 15;56(6):811-825.e6. Epub 2021 Mar 15.

Department of Biology, School of Life Sciences, Brain Research Center, Southern University of Science and Technology, Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Shenzhen 518055, People's Republic of China. Electronic address:

Neuronal activity increases energy consumption and requires balanced production to maintain neuronal function. How activity is coupled to energy production remains incompletely understood. Here, we report that Rheb regulates mitochondrial tricarboxylic acid cycle flux of acetyl-CoA by activating pyruvate dehydrogenase (PDH) to increase ATP production. Rheb is induced by synaptic activity and lactate and dynamically trafficked to the mitochondrial matrix through its interaction with Tom20. Mitochondria-localized Rheb protein is required for activity-induced PDH activation and ATP production. Cell-type-specific gain- and loss-of-function genetic models for Rheb reveal reciprocal changes in PDH phosphorylation/activity, acetyl-CoA, and ATP that are not evident with genetic or pharmacological manipulations of mTORC1. Mechanistically, Rheb physically associates with PDH phosphatase (PDP), enhancing its activity and association with the catalytic E1α-subunit of PDH to reduce PDH phosphorylation and increase its activity. Findings identify Rheb as a nodal point that balances neuronal activity and neuroenergetics via Rheb-PDH axis.
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http://dx.doi.org/10.1016/j.devcel.2021.02.022DOI Listing
March 2021

Quantify the combined effects of temperature and force on the stability of DNA hairpin.

J Phys Condens Matter 2021 Mar 12. Epub 2021 Mar 12.

College of Physics, Guizhou University, Huaxi District, Guiyang City, Guizhou Province,, Guiyang, Guizhou, 550025, CHINA.

Ox-DNA, as a successful coarse-grain model, has been applied to reproduce the thermodynamic and mechanical properties of both single- and double-stranded DNA. In current simulation, ox-DNA is extended to explore the combined effects of temperature and force on the stability of DNA hairpin and its free energy landscape. Simulations were carried out at different forces and temperatures, at each temperature, a 18-base-pair DNA hairpin dynamically transited between folded state and unfolded state, and the separation between two states is consistent with the full contour length of single-stranded DNA in the unfolded state. Two methods were used to identify the critical force of DNA hairpin at each temperature and the critical forces obtained from two methods were consistent with each other and gradually decreased with the increasing temperature from 300K to 326K. The critical force at 300K is reasonably consistent with the single molecule result of DNA hairpin with the same stem length. The two-state free energy landscape can be elucidated from the probability distribution of DNA hairpin extension and its dependence on the force and temperature is totally different. The increasing temperature not only reduces the free energy barrier, but also alters the position of transition point along the extension coordinate, resulting in the reduction of folding distance and the extension of unfolding distance, but their sum is not obviously dependent on the temperature. Generally, an assumption that the location of transition state in two-state energy landscape is independent of the stretching force is used to analyze the data of the single molecule experiment, but current simulation results indicate that effects of stretching forces on the location of transition state in two-state energy landscape are dependent on temperature. At relatively high temperature, stretching force can also change the location of transition state in the free energy landscape.
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http://dx.doi.org/10.1088/1361-648X/abee38DOI Listing
March 2021

A novel missense mutation in the HSF4 gene of giant pandas with senile congenital cataracts.

Sci Rep 2021 Mar 8;11(1):5411. Epub 2021 Mar 8.

Strait (Fuzhou) Giant Panda Research and Exchange Centers, Fuzhou, China.

Cataracts are a common cause of visual impairment and blindness in mammals. They are usually associated with aging, but approximately one third of cases have a significant genetic component. Cataracts are increasingly prevalent among aging populations of captive giant pandas (Ailuropoda melanoleuca) and it is therefore important to identify genetic determinants that influence the likelihood of cataract development in order to distinguish between congenital and age-related disease. Here we screened for cataract-related genetic effects using a functional candidate gene approach combined with bioinformatics to identify the underlying genetic defect in a giant panda with congenital cataracts. We identified a missense mutation in exon 10 of the HSF4 gene encoding heat shock transcription factor 4. The mutation causes the amino acid substitution R377W in a highly conserved segment of the protein between the isoform-specific and downstream hydrophobic regions. Predictive modeling revealed that the substitution is likely to increase the hydrophobicity of the protein and disrupt interactions with spatially adjacent amino acid side chains. The mutation was not found in 13 unaffected unrelated animals but was found in an unrelated animal also diagnosed with senile congenital cataract. The novel missense mutation in the HSF4 gene therefore provides a potential new genetic determinant that could help to predict the risk of cataracts in giant pandas.
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http://dx.doi.org/10.1038/s41598-021-84741-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940430PMC
March 2021

Effects of patient decision aids in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

Int J Nurs Pract 2021 Mar 3:e12914. Epub 2021 Mar 3.

School of Nursing, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Aims: This study aimed to systematically evaluate the effectiveness of patient decision aids on knowledge, decisional conflict and decisional self-efficacy outcomes in patients with diabetes.

Methods: A comprehensive database search was performed using the Web of Science, Cochrane Library, PubMed, Embase, PsycINFO (Ovid), CINAHL (EBASCO), CNKI, VIP, Wan Fang Database and the Ottawa Decision Aid Library Inventory (http://decisionaid.ohri.ca/index.html) from inception to 13 October 2019. Two reviewers independently searched databases, screened articles, extracted data and evaluated the risk bias of included studies. Then Rev Man 5.3 software was adopted for statistical analysis.

Results: Ten articles containing 1,452 people with diabetes were selected. The results of meta-analysis showed that patient decision aids had a positive effect on reducing decisional conflict and improving decisional self-efficacy among patients with type 2 diabetes. Meanwhile, this article also revealed that patient decision aids have beneficial short-term effects on improving knowledge, but there was no significant long-term effect.

Conclusion: Patient decision aids are capable of becoming support tools to improve shared decision making. Further implementation studies are required to transform patient decision aids tools into clinical practice.
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http://dx.doi.org/10.1111/ijn.12914DOI Listing
March 2021

Emodin resists to Cyprinid herpesvirus 3 replication via the pathways of Nrf2/Keap1-ARE and NF-κB in the ornamental koi carp (Cyprinus carpio haematopterus).

Comp Biochem Physiol C Toxicol Pharmacol 2021 Feb 26:109023. Epub 2021 Feb 26.

College of Animal Sciences, Jilin Agricultural University, Changchun, Jilin 130118, China. Electronic address:

Cyprinid herpesvirus 3 (CyHV-3) causes high mortality in carp. Emodin has been shown of the effects of antioxidant, anti-inflammatory and antiviral. In present study, we investigated the preventive effects and mechanism of emodin on CyHV-3 infection. The ornamental koi carp (Cyprinus carpio haematopterus) were intraperitoneally injected with emodin (10 mg/kg, 20 mg/kg, or 40 mg/kg). 72 h later, an intraperitoneal injection of CyHV-3 was administered, and collected the samples one week later to detect the antioxidant parameters, antioxidant genes, inflammatory genes and to perform histopathology assays. The results showed that emodin significantly suppressed CyHV-3 replication (P < 0.05), improved the koi survival rate and slowed the damage caused by CyHV-3. Emodin treatment increased the antioxidant activity and decreased the lipid peroxidation level of the koi. Compared to the CyHV-3 group, emodin treatment resulted in the same antioxidant parameters after CyHV-3 infection. Emodin treatment activated the Nuclear factorery throid 2-related factor 2/Kelch-like ECH-associated protein 1-antioxidatant response element (Nrf2/Keap1-ARE) pathway and upregulated the expression of heme oxygenase 1 (HO-1), superoxide dismutase (SOD), and catalase (CAT) in the hepatopancreas after CyHV-3 infection. Emodin activated the nuclear factor kappa-B (NF-κB) pathway and decreased the expression of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) in the koi induced by CyHV-3. In conclusion, emodin treatment can suppress CyHV-3 replication and reduce the mortality of koi caused by CyHV-3. Emodin improves antioxidant function, relieves oxidative stress and inflammation cytokines via Nrf2/Keap1-ARE and NF-κB pathways, and protects against the adverse effects induced by CyHV-3.
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http://dx.doi.org/10.1016/j.cbpc.2021.109023DOI Listing
February 2021

Cathepsin B-responsive and gadolinium-labeled branched glycopolymer-PTX conjugate-derived nanotheranostics for cancer treatment.

Acta Pharm Sin B 2021 Feb 14;11(2):544-559. Epub 2020 Aug 14.

Huaxi MR Research Center (HMRRC), Department of Neurosurgery, and Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.
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http://dx.doi.org/10.1016/j.apsb.2020.07.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893117PMC
February 2021

Extrusion of the Distal End of Ventriculoperitoneal Shunt through the Urethral Orifice in an Adult Male.

Neurol India 2021 Jan-Feb;69(1):230-231

Department of Neurosurgery, West China Hospital of Sichuan University, Sichuan, People's Republic of China.

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http://dx.doi.org/10.4103/0028-3886.310091DOI Listing
March 2021

Clinicopathological characteristics and treatment outcomes of epithelioid glioblastoma.

Neurosurg Rev 2021 Feb 17. Epub 2021 Feb 17.

Department of Neurosurgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, China.

Epithelioid glioblastoma is a new variant of glioblastoma that has been recently recognized in the 2016 WHO classification of brain tumors. Given the rarity of epithelioid glioblastoma, the clinical characteristics, pathological features, radiological findings, and treatment outcomes are still not well characterized. Therefore, we identified eighty-four epithelioid glioblastoma cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 55 male and 29 female patients with a mean age of 33.6 years. Headache (77.3%) was the most common clinical symptom, and other common symptoms included nausea or vomiting (34%), dizziness (20.5%), seizures (13.6%), and limb weakness (13.6%). Most lesions (88.1%) were located in cerebral lobes, especially in the frontal lobe and temporal lobe. One hundred percent of the patients were IDH1 wild-type (75/75) and INI-1 positive (58/58), and 57.3% (47/82) of patients harbored BRAF mutation. The median overall survival (OS) of all patients was 10.5 months. Patients who received chemotherapy (p = 0.006) or radiotherapy (p = 0.022) had a longer survival than patients who did not. In addition, the K-M curve showed that the BRAF mutation status was not associated with survival (p = 0.724). These findings may assist clinicians with better understanding and management of epithelioid glioblastoma.
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http://dx.doi.org/10.1007/s10143-021-01492-7DOI Listing
February 2021

Observations and modeling of OH and HO radicals in Chengdu, China in summer 2019.

Sci Total Environ 2021 Jun 27;772:144829. Epub 2021 Jan 27.

State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing, China; International Joint laboratory for Regional pollution Control (IJRC), Peking University, Beijing, China; Beijing Innovation Center for Engineering Sciences and Advanced Technology, Peking University, Beijing, China; CAS Center for Excellence in Regional Atmospheric Environment, Chinese Academy of Science, Xiamen, China. Electronic address:

This study reports on the first continuous measurements of ambient OH and HO radicals at a suburban site in Chengdu, Southwest China, which were collected during 2019 as part of a comprehensive field campaign 'CompreHensive field experiment to explOre the photochemical Ozone formation mechaniSm in summEr - 2019 (CHOOSE-2019)'. The mean concentrations (11:00-15:00) of the observed OH and HO radicals were 9.5 × 10 and 9.0 × 10 cm, respectively. To investigate the state-of-the-art chemical mechanism of radical, closure experiments were conducted with a box model, in which the RACM2 mechanism updated with the latest isoprene chemistry (RACM2-LIM1) was used. In the base run, OH radicals were underestimated by the model for the low-NO regime, which was likely due to the missing OH recycling. However, good agreement between the observed and modeled OH concentrations was achieved when an additional species X (equivalent to 0.25 ppb of NO mixing ratio) from one new OH regeneration cycle (RO + X → HO, HO + X → OH) was added into the model. Additionally, in the base run, the model could reproduce the observed HO concentrations. Discrepancies in the observed and modeled HO concentrations were found in the sensitivity runs with HO heterogeneous uptake, indicating that the impact of the uptake may be less significant in Chengdu because of the relatively low aerosol concentrations. The ROx (= OH + HO + RO) primary source was dominated by photolysis reactions, in which HONO, O, and HCHO photolysis accounted for 34%, 19%, and 23% during the daytime, respectively. The efficiency of radical cycling was quantified by the radical chain length, which was determined by the NO to NO ratio successfully. The parameterization of the radical chain length may be very useful for the further determinations of radical recycling.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144829DOI Listing
June 2021

Regulation of CRMP2 by Cdk5 and GSK-3β participates in sevoflurane-induced dendritic development abnormalities and cognitive dysfunction in developing rats.

Toxicol Lett 2021 May 3;341:68-79. Epub 2021 Feb 3.

Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China; Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

Background: General anesthetics such as sevoflurane interfere with dendritic development and synaptogenesis, resulting in cognitive impairment. The collapsin response mediator protein2 (CRMP2) plays important roles in dendritic development and synaptic plasticity and its phosphorylation is regulated by cycline dependent kinase-5 (Cdk5) and glycogen synthase kinase-3β (GSK-3β). Here we investigated whether Cdk5/CRMP2 or GSK-3β/CRMP2 pathway is involved in sevoflurane-induced developmental neurotoxicity.

Methods: Rats at postnatal day 7 (PND7) were i.p. injected with Cdk5 inhibitor roscovitine, GSK-3β inhibitor SB415286 or saline 20 min. before exposure to 2.8% sevoflurane for 4 h. Western-blotting was applied to measure the expression of Cdk5/CRMP2 and GSK-3β/CRMP2 pathway proteins in the hippocampus 6 h after the sevoflurane exposure. When rats grew to adolescence (from PND25), they were tested for open-field and contextual fear conditioning, and then long term potentiation (LTP) from hippocampal slices was recorded, and morphology of pyramidal neuron was examined by Golgi staining and synaptic plasticity-related proteins expression in hippocampus were measured by western-blotting. In another batch of experiment, siRNA-CRMP2 or vehicle control was injected into hippocampus on PND5.

Results: Sevoflurane activated Cdk5/CRMP2 and GSK-3β/CRMP2 pathways in the hippocampus of neonatal rats, reduced dendritic length, branches and the density of dendritic spine in pyramidal neurons. It also reduced the expressions of PSD-95, drebrin and synaptophysin in hippocampus, impaired memory ability of rats and inhibited LTP in hippocampal slices. All the impairment effects by sevoflurane were attenuated by pretreatment with inhibitor of Cdk5 or GSK-3β. Furthermore, rat transfected with siRNA-CRMP2 eliminated the neuroprotective effects of Cdk5 or GSK-3β blocker in neurobehavioral and LTP tests.

Conclusion: Cdk5/CRMP2 and GSK-3β/CRMP2 pathways participate in sevoflurane-induced dendritic development abnormalities and cognitive dysfunction in developing rats.
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http://dx.doi.org/10.1016/j.toxlet.2021.01.023DOI Listing
May 2021

Effect of boiling and frying on the selenium content, speciation, and in vitro bioaccessibility of selenium-biofortified potato (Solanum tuberosum L.).

Food Chem 2021 Jun 19;348:129150. Epub 2021 Jan 19.

College of Food Science and Engineering, South China University of Technology, Wushan Road 381, Guangzhou 510640, China. Electronic address:

Selenium-enriched potato is a good supplement for selenium-deficient populations. This study evaluated the influence of two most common cooking methods, including boiling and frying, on selenium content, speciation, and in vitro bioaccessibility of selenium-biofortified potato tubers. After foliar application of 200 μg/mL sodium selenite, potato tubers with 1.33 μg Se/g were obtained. Peeling resulted in 53.4%-69.9% loss of selenium in tubers. The total selenium content decreased by approximately 43.3% after boiling, among which up to 38.5% of the lost selenium is found in the boiling water. Nearly 31.7% of selenium was lost via volatilization during frying. Both cooking methods significantly enhanced the bioaccessibility of Se(IV) in tubers. Whereas SeMeCys became less bioaccessible after boiling. SeMet and SeCys in fired tubers were not accessible after digestion. This study suggested that boiling is more appropriate for cooking selenium-enriched potatoes.
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http://dx.doi.org/10.1016/j.foodchem.2021.129150DOI Listing
June 2021

Inhibition of mitochondrial carrier homolog 2 (MTCH2) suppresses tumor invasion and enhances sensitivity to temozolomide in malignant glioma.

Mol Med 2021 01 28;27(1). Epub 2021 Jan 28.

Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

Background: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma.

Methods: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy.

Results: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling.

Conclusion: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.
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http://dx.doi.org/10.1186/s10020-020-00261-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842075PMC
January 2021

Novel PHOX2B germline mutation in childhood medulloblastoma: a case report.

Hered Cancer Clin Pract 2021 Jan 19;19(1):12. Epub 2021 Jan 19.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Background: Medulloblastoma is an aggressive brain tumor mostly found in children, few studies on pathogenic germline mutations predisposing this disease was reported.

Case Presentation: We present an 11-year-old male with medulloblastoma, who harbors a de novo PHOX2B germline mutation as detected by whole exome sequencing (WES). Family history was negative. Sanger sequencing confirmed this mutation in peripheral blood, hair bulbs, urine and saliva. Identification of novel germline mutations is beneficial for childhood cancer screening.

Conclusions: This case revealed a de novo PHOX2B germline mutation as a potential cause of medulloblastoma in a child and suggests familial germline variant screening is useful when an affected family is considering having a second child.
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http://dx.doi.org/10.1186/s13053-021-00170-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816394PMC
January 2021

Development of stretchable metallic glass electrodes.

Nanoscale 2021 Jan;13(3):1800-1806

Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

Stretchable electrodes are essential components for wearable electronics. However, the stretchability of the electrodes is often achieved with the sacrifice of electronic conductivity along with huge variation in resistance. In this work, stretchable metallic glass electrodes (MG-electrodes) that have both high electronic conductivity and excellent electronic stability are developed. The stretchability of the MG-electrode is significantly improved by shrinking MG films deposited on substrates with pre-strain. We demonstrate two types of MG-electrodes. One is a transparent MG-electrode for uniaxial stretching, and the other with better conductivity is for biaxial stretching. Compared with previous electrodes, the MG-electrodes exhibit a combination of high conductivity and negligible resistivity change (<5%), making them promising candidates for interconnections. Along with the excellent corrosion resistance of metallic glasses, the electrodes may be used in harsh environments.
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http://dx.doi.org/10.1039/d0nr07307eDOI Listing
January 2021

[Clinical and genetic analysis of a novel CHD4 gene variant in a Chinese patient with Sifrim-Hitz-Weiss syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jan;38(1):63-66

Dongguan Maternal and Child Health Care Hospital, Dongguan, Guangdong 523120, China.

Objective: To explore the genotype-phenotype correlation of a case with Sifrim-Hitz-Weiss syndrome (SIHIWES) caused by a novel CHD4 gene variant.

Methods: Genomic DNA was extracted from peripheral blood samples of the patient and her parents. Whole-exome sequencing (WES) was carried out for the patient.Suspected variant was verified by Sanger sequencing.

Results: The proband, a 2-year-old Chinese girl, presented with global developmental delay, intellectual disability, distinctive facial features and multiple congenital anomalies. Her prenatal manifestations included increased nuchal thickness, cranial and facial anomalies, and decreased fetal movement. WES has identified a novel variant in the CHD4 gene, namely NM_001273:c.2989C>G (p.Leu997Val) (GRCh37/hg19).Comparison of her phenotype with previously reported SIHIWES cases suggested that our patient's prenatal presentations were unreported before, with novel features including funduscopic anomaly, facial dysmorphisms such as asymmetrical ears, drooping eyelid, long philtrum and downturned mouth.

Conclusion: Above findings have expanded the mutational spectrum of the CHD4 gene and revealed novel phenotypes in Chinese patients with SIHIWES.
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http://dx.doi.org/10.3760/cma.j.cn511374-20191120-00594DOI Listing
January 2021

CNV profiles of Chinese pediatric patients with developmental disorders.

Genet Med 2021 Apr 5;23(4):669-678. Epub 2021 Jan 5.

Department of Genetics, Capital Institute of Pediatrics, Beijing, China.

Purpose: To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders.

Methods: De-identified chromosomal microarray (CMA) data from 10,026 pediatric patients with developmental disorders were collected for re-evaluating the pathogenic CNV (pCNV) yields of different medical conditions and for comparing the frequency and phenotypic variability of genomic disorders between the Chinese and Western patient populations.

Results: The overall yield of pCNVs in the Chinese pediatric patient cohort was 21.37%, with variable yields for different disorders. Yields of pCNVs were positively associated with phenotypic complexity and intellectual disability/developmental delay (ID/DD) comorbidity for most disorders. The genomic burden and pCNV yield in neurodevelopmental disorders supported a female protective effect. However, the stratification analysis revealed that it was seen only in nonsyndromic ID/DD, not in nonsyndromic autism spectrum disorders or seizure. Furthermore, 15 known genomic disorders showed significantly different frequencies in Chinese and Western patient cohorts, and profiles of referred clinical features for 15 known genomic disorders were also significantly different in the two cohorts.

Conclusion: We defined the pCNV yields and profiles of the Chinese pediatric patients with different medical conditions and uncovered differences in the frequency and phenotypic diversity of genomic disorders between Chinese and Western patients.
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http://dx.doi.org/10.1038/s41436-020-01048-yDOI Listing
April 2021

Multi-Omics Analysis Reveals Novel Subtypes and Driver Genes in Glioblastoma.

Front Genet 2020 26;11:565341. Epub 2020 Nov 26.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

Glioblastoma is the most lethal malignant primary brain tumor; nevertheless, there remains a lack of accurate prognostic markers and drug targets. In this study, we analyzed 117 primary glioblastoma patients' data that contained SNP, DNA copy, DNA methylation, mRNA expression, and clinical information. After the quality of control examination, we conducted the single nucleotide polymorphism (SNP) analysis, copy number variation (CNV) analysis, and infiltrated immune cells estimate. And moreover, by using the cluster of cluster analysis (CoCA) methods, we finally divided these GBM patients into two novel subtypes, HX-1 (Cluster 1) and HX-2 (Cluster 2), which could be co-characterized by 3 methylation variable positions [cg16957313(DUSP1), cg17783509(PHOX2B), cg23432345(HOXA7)] and 15 (PCDH1, CYP27B1, LPIN3, GPR32, BCL6, OR4Q3, MAGI3, SKIV2L, PCSK5, AKAP12, UBE3B, MAP4, TP53BP1, F5, RHOBTB1) gene mutations pattern. Compared to HX-1 subtype, the HX-2 subtype was identified with higher gene co-occurring events, tumor mutation burden (TBM), and poor median overall survival [231.5 days (HX-2) vs. 445 days (HX-1), -value = 0.00053]. We believe that HX-1 and HX-2 subtypes may make sense as the potential prognostic biomarkers for patients with glioblastoma.
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http://dx.doi.org/10.3389/fgene.2020.565341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726196PMC
November 2020

Pineal Region Glioblastomas: Clinical Characteristics, Treatment, and Survival Outcome.

World Neurosurg 2021 Feb 10;146:e799-e810. Epub 2020 Nov 10.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China; West China Glioma Centre, West China Hospital, Sichuan University, Chengdu, China.

Objective: Given the rarity of patients with pineal glioblastoma (GBM), clinical characteristics, treatment, and prognostic factors are not well characterized. This study aimed to investigate these characteristics and identify the prognostic factors of overall survival (OS).

Methods: A retrospective analysis of newly diagnosed patients with pineal GBM, including our 3 cases and an additional 44 cases from published articles, was conducted. Survival analysis was performed by Kaplan-Meier analysis and Cox regression analysis was used to determine the prognostic factors.

Results: A total of 47 patients (28 males and 19 females) were enrolled, with a median age of 46 years (range, 5-74 years). Forty-four patients (90.9%) had preoperative obstructive hydrocephalus. Among 38 patients, 21 (55.3%) had distal leptomeningeal dissemination. Forty-five patients (95.7%) had resection/biopsy, 6 of whom had gross total resection, 22 had subtotal resection, 7 had partial resection, and 10 had biopsy. Adjuvant therapy included radiotherapy in 36 patients and chemotherapy in 27 patients. The median OS was 10.0 months. The 6-month, 1-year, and 2-year survival was 68.0%, 42.6%, and 17.0%, respectively. Cox regression analysis showed that patients receiving biopsy (P = 0.042) or chemotherapy (P = 0.029) had the better OS and these were regarded as independent prognostic factors. Further survival analysis showed that chemoradiotherapy had better survival benefit than other regimens.

Conclusions: In this study, we summarized the characteristics of patients with pineal GBM and showed the correlation between clinical characteristics and prognosis. This study may give readers a deep understanding of these rare GBMs and provide some references for future management.
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http://dx.doi.org/10.1016/j.wneu.2020.11.016DOI Listing
February 2021

Low Mannitol Concentrations in Expressing Genes Improve Salt Tolerance.

Plants (Basel) 2020 Nov 7;9(11). Epub 2020 Nov 7.

Marine Bioproducts Research Laboratory, Department of Plant, Food and Environmental Sciences, Dalhousie University, Truro, NS B2N 5E3, Canada.

Mannitol is abundant in a wide range of organisms, playing important roles in biotic and abiotic stress responses. Nonetheless, mannitol is not produced by a vast majority of plants, including many important crop plants. Mannitol-producing transgenic plants displayed improved tolerance to salt stresses though mannitol production was rather low, in the µM range, compared to mM range found in plants that innately produce mannitol. Little is known about the molecular mechanisms underlying salt tolerance triggered by low concentrations of mannitol. Reported here is the production of mannitol in , by expressing two mannitol biosynthesis genes from the brown alga sp. strain Ec32. To date, no brown algal genes have been successfully expressed in land plants. Expression of mannitol-1-phosphate dehydrogenase and mannitol-1-phosphatase genes was associated with the production of 42.3-52.7 nmol g fresh weight of mannitol, which was sufficient to impart salinity and temperature stress tolerance. Transcriptomics revealed significant differences in the expression of numerous genes, in standard and salinity stress conditions, including genes involved in K homeostasis, ROS signaling, plant development, photosynthesis, ABA signaling and secondary metabolism. These results suggest that the improved tolerance to salinity stress observed in transgenic plants producing mannitol in µM range is achieved by the activation of a significant number of genes, many of which are involved in priming and modulating the expression of genes involved in a variety of functions including hormone signaling, osmotic and oxidative stress, and ion homeostasis.
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http://dx.doi.org/10.3390/plants9111508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695032PMC
November 2020

Recent Advances in Understandings Towards Pathogenesis and Treatment for Intrauterine Adhesion and Disruptive Insights from Single-Cell Analysis.

Reprod Sci 2020 Oct 30. Epub 2020 Oct 30.

Dongguan Maternal and Child Health Care Hospital, Dongguan, 523120, China.

Intrauterine adhesion is a major cause of menstrual irregularities, infertility, and recurrent pregnancy losses and the progress towards its amelioration and therapy is slow and unsatisfactory. We aim to summarize and evaluate the current treatment progress and research methods for intrauterine adhesion. We conducted literature review in January 2020 by searching articles at PubMed on prevention and treatment, pathogenesis, the repair of other tissues/organs, cell plasticity, and the stem cell-related therapies for intrauterine adhesion. A total of 110 articles were selected for review. Uterine cell heterogeneity, expression profile, and cell-cell interaction were investigated based on scRNA-seq of uterus provided by Human Cell Landscape (HCL) project. Previous knowledge on intrauterine adhesion (IUA) pathogenesis was mostly derived from correlation studies by differentially expressed genes between endometrial tissue of intrauterine adhesion patients/animal models and normal endometrial tissue. Although the TGF-β1/SMAD pathway was suggested as the key driver for IUA pathogenesis, uterine cell heterogeneity and distinct expression profile among different cell types highlighted the importance of single-cell investigations. Cell-cell interaction in the uterus revealed the central hub of endothelial cells interacting with other cells, with endothelial cells in endothelial to mesenchymal transition and fibroblasts as the strongest interaction partners. The potential of stem cell-related therapies appeared promising, yet suffers from largely animal studies and nonstandard study design. The need to dissect the roles of endometrial cells, endothelial cells, and fibroblasts and their interaction is evident in order to elucidate the molecular and cellular mechanisms in both intrauterine adhesion pathogenesis and treatment.
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http://dx.doi.org/10.1007/s43032-020-00343-yDOI Listing
October 2020

The bZIP Transcription Factor GmbZIP15 Negatively Regulates Salt- and Drought-Stress Responses in Soybean.

Int J Mol Sci 2020 Oct 21;21(20). Epub 2020 Oct 21.

Key Lab of Genetics, Breeding and Multiple Utilization of Crops, Ministry of Education, State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Center for Genomics and Biotechnology, College of Plant Protection, College of Life Sciences, College of Crop Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

Soybean (), as an important oilseed crop, is constantly threatened by abiotic stress, including that caused by salinity and drought. bZIP transcription factors (TFs) are one of the largest TF families and have been shown to be associated with various environmental-stress tolerances among species; however, their function in abiotic-stress response in soybean remains poorly understood. Here, we characterized the roles of soybean transcription factor GmbZIP15 in response to abiotic stresses. The transcript level of was suppressed under salt- and drought-stress conditions. Overexpression of in soybean resulted in hypersensitivity to abiotic stress compared with wild-type (WT) plants, which was associated with lower transcript levels of stress-responsive genes involved in both abscisic acid (ABA)-dependent and ABA-independent pathways, defective stomatal aperture regulation, and reduced antioxidant enzyme activities. Furthermore, plants expressing a functional repressor form of exhibited drought-stress resistance similar to WT. RNA-seq and qRT-PCR analyses revealed that positively regulates expression and negatively regulates and expression in response to abiotic stress. Overall, these data indicate that GmbZIP15 functions as a negative regulator in response to salt and drought stresses.
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http://dx.doi.org/10.3390/ijms21207778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589023PMC
October 2020

Transmission of SARS-CoV-2 in the Karaoke Room: An Outbreak of COVID-19 in Guangzhou, China, 2020.

J Epidemiol Glob Health 2021 03 12;11(1):6-9. Epub 2020 Oct 12.

Guangzhou Center for Disease Control and Prevention, Guanghzou, Guangdong Province, China.

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http://dx.doi.org/10.2991/jegh.k.201007.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958275PMC
March 2021

Novel Chinese Angelica Polysaccharide Biomimetic Nanomedicine to Curcumin Delivery for Hepatocellular Carcinoma Treatment and Immunomodulatory Effect.

Phytomedicine 2021 Jan 25;80:153356. Epub 2020 Sep 25.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, P.R. China; State Key Laboratory of Bio-Fibers and Eco-Textiles,Qingdao University, Qingdao, Shandong, 266071, P.R. China; Weifang Institute of Chinese Medical Sciences and Industrial Technology, Weifang 261100, P.R.China. Electronic address:

Background: Using natural polysaccharides from Traditional Chinese Medicine as nanodrug delivery systems have considerable potential for tumor diagnostics and therapeutics.

Purpose: On the basis of targeted therapy and combining the advantages of natural polysaccharides (angelica polysaccharide, APS) and natural Chinese medicine (curcumin, Cur) to design functionalized nanoparticles to improve the therapeutic through cell membrane encapsulation and immunotherapy.

Study Design And Methods: Cur-loaded, glycyrrhetic acid (GA)-APS-disulfide bond (DTA)-Cur nanomicelle (GACS-Cur), which were prepared by the dialysis method. GACS-Cur was encapsulated with the membranes from red blood cells (RBCm) termed GACS-Cur@RBCm, which were prepared by the principle of extrusion using a miniature extruder. The developed formulations were subjected to various in vitro and in vivo evaluation tests.

Results: The resulting APS nanocarriers supported a favorable drug-loading capacity, biocompatibility, and enhanced synergistic anti-hepatoma effects both in vitro and in vivo. After administration in mice, in vivo imaging results showed that the GACS-Cur and RBCm-coated groups had an obvious stronger tumor tissue targeting ability than the control treatment groups. Additionally, the immunomodulatory effect increased IL-12, TNF-α and IFN-γ expression and CD8+ T cell infiltration (1.9-fold) than that of the saline group. Notably, in comparison with hyaluronic acid (HA) nanocarriers, APS nanocarriers possess higher anti-hepatoma efficiency and targeting capabilities and, thus, should be further studied for a wide range of anti-cancer applications.

Conclusion: Our data demonstrated that APS nanocarriers encapsulated with erythrocyte membrane mighty be a promising clinical method in the development of efficacy, safety and targeting of liver cancer therapy.
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http://dx.doi.org/10.1016/j.phymed.2020.153356DOI Listing
January 2021

Genome-wide identification and expression analysis of the ERF transcription factor family in pineapple ( (L.) Merr.).

PeerJ 2020 22;8:e10014. Epub 2020 Sep 22.

State Key Lab of Ecological Pest Control for Fujian and Taiwan Crops; Key Lab of Genetics, Breeding and Multiple Utilization of Crops, Ministry of Education; Fujian Provincial Key Lab of Haixia Applied Plant Systems Biology, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, China.

Pineapple ( (L.) Merr.) is an important tropical fruit with high economic value. The quality and yield of pineapple will be affected by various environmental conditions. Under adverse conditions, plants can produce a complex reaction mechanism to enhance their resistance. It has been reported that the member of ethylene responsive transcription factors (ERFs) plays a crucial role in plant developmental process and stress response. However, the function of these proteins in pineapple remains limited. In this study, a total of 74 genes ) were identified in pineapple genome, named from to , and divided into 13 groups based on phylogenetic analysis. We also analyzed gene structure, conserved motif and chromosomal location of , and the within the same group possess similar gene structures and motif compositions. Three genes (, and ) were present on unanchored scaffolds, so they could not be conclusively mapped on chromosome. Synteny and -elements analysis of genes provided deep insight into the evolution and function of pineapple genes. Furthermore, we analyzed the expression profiling of in different tissues and developmental stages, and 22 genes were expressed in all examined tissues, in which five genes (, , , , and ) had high expression levels. Additionally, nine genes were selected for functional verification by qRT-PCR. These results provide useful information for further investigating the evolution and functions of ERF family in pineapple.
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http://dx.doi.org/10.7717/peerj.10014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518161PMC
September 2020

Anti-CASPR2 antibody associated encephalitis with anosmia and demyelinating pseudotumor: A case report.

J Neuroimmunol 2020 11 12;348:577393. Epub 2020 Sep 12.

Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, PR China. Electronic address:

A 20-year-old female presented with fine motor deficits and visual field defect was admitted to our hospital. CSF tests for autoimmune encephalitis antibodies and onconeuronal antibodies were unremarkable. MRI showed unilateral lesion involving left basal ganglia, external capsule, insula, hippocampus, and amygdala, which was considered to be demyelinating pseudotumor after surgical intervention. The patient's symptoms relieved so she didn't consent to immunotherapy. Two years and a half later our patient reported sudden anosmia. Reexamination by MRI demonstrated a new lesion. We then detected anti-CASPR2 antibodies in the patient's serum and gave her immunotherapy.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577393DOI Listing
November 2020

Floral transcriptomes reveal gene networks in pineapple floral growth and fruit development.

Commun Biol 2020 Sep 10;3(1):500. Epub 2020 Sep 10.

Key Laboratory of Genetics, Breeding and Multiple Utilization of Crops, Ministry of Education, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, College of Life Sciences, College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

Proper flower development is essential for sexual reproductive success and the setting of fruits and seeds. The availability of a high quality genome sequence for pineapple makes it an excellent model for studying fruit and floral organ development. In this study, we sequenced 27 different pineapple floral samples and integrated nine published RNA-seq datasets to generate tissue- and stage-specific transcriptomic profiles. Pairwise comparisons and weighted gene co-expression network analysis successfully identified ovule-, stamen-, petal- and fruit-specific modules as well as hub genes involved in ovule, fruit and petal development. In situ hybridization confirmed the enriched expression of six genes in developing ovules and stamens. Mutant characterization and complementation analysis revealed the important role of the subtilase gene AcSBT1.8 in petal development. This work provides an important genomic resource for functional analysis of pineapple floral organ growth and fruit development and sheds light on molecular networks underlying pineapple reproductive organ growth.
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http://dx.doi.org/10.1038/s42003-020-01235-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483743PMC
September 2020