Publications by authors named "Zhen Chen"

1,312 Publications

  • Page 1 of 1

Oxygen-Containing Functional Groups Regulating the Carbon/Electrolyte Interfacial Properties Toward Enhanced K Storage.

Nanomicro Lett 2021 Sep 13;13(1):192. Epub 2021 Sep 13.

College of Materials Science and Engineering, Hunan Joint International Laboratory of Advanced Materials and Technology of Clean Energy, Hunan Province Key Laboratory for Advanced Carbon Materials and Applied Technology, Hunan University, Changsha, 410082, People's Republic of China.

Oxygen-containing functional groups were found to effectively boost the K storage performance of carbonaceous materials, however, the mechanism behind the performance enhancement remains unclear. Herein, we report higher rate capability and better long-term cycle performance employing oxygen-doped graphite oxide (GO) as the anode material for potassium ion batteries (PIBs), compared to the raw graphite. The in situ Raman spectroscopy elucidates the adsorption-intercalation hybrid K storage mechanism, assigning the capacity enhancement to be mainly correlated with reversible K adsorption/desorption at the newly introduced oxygen sites. It is unraveled that the C=O and COOH rather than C-O-C and OH groups contribute to the capacity enhancement. Based on in situ Fourier transform infrared (FT-IR) spectra and in situ electrochemical impedance spectroscopy (EIS), it is found that the oxygen-containing functional groups regulate the components of solid electrolyte interphase (SEI), leading to the formation of highly conductive, intact and robust SEI. Through the systematic investigations, we hereby uncover the K storage mechanism of GO-based PIB, and establish a clear relationship between the types/contents of oxygen functional groups and the regulated composition of SEI.
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http://dx.doi.org/10.1007/s40820-021-00722-3DOI Listing
September 2021

Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway.

Front Physiol 2021 27;12:703281. Epub 2021 Aug 27.

Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aims: Obstructive sleep apnea (OSA) is a risk factor for steroid-resistant (SR) asthma. However, the underlying mechanism is not well defined. This study aimed to investigate how chronic intermittent hypoxia (CIH), the main pathophysiology of OSA, influenced the effects of glucocorticoids (GCs) on asthma.

Main Methods: The effects of dexamethasone (Dex) were determined using the ovalbumin (OVA)-challenged mouse model of asthma and transforming growth factor (TGF)-β treated airway smooth muscle cells (ASMCs), with or without CIH. The p38 MAPK signaling pathway activity was then detected in the mouse ( = 6) and ASMCs models ( = 6), which were both treated with the p38 MAPK inhibitor SB239063.

Key Findings: Under CIH, mouse pulmonary resistance value, inflammatory cells in bronchoalveolar lavage fluid (BALF), and inflammation scores increased in OVA-challenged combined with CIH exposure mice compared with OVA-challenged mice ( < 0.05). These indicators were similarly raised in the OVA + CIH + Dex group compared with the OVA + Dex group ( < 0.05). CIH exposure enhanced the activation of the p38 MAPK pathway, oxidative stress injury, and the expression of NF-κB both in lung tissue and ASMCs, which were reversed by treatment with Dex and SB239063. In the study, treatment with Dex and SB239063 decreased ASMCs proliferation induced by TGF-β combined with CIH and suppressed activation of the p38 MAPK pathway, oxidative stress injury, and NF-κB nuclear transcription ( < 0.05).

Significance: These results indicated that CIH decreased GC sensitivity by activating the p38 MAPK signaling pathway.
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http://dx.doi.org/10.3389/fphys.2021.703281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430218PMC
August 2021

Therapeutic Targeting of Hepatic ACSL4 Ameliorates Non-alcoholic Steatohepatitis in Mice.

Hepatology 2021 Sep 12. Epub 2021 Sep 12.

Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, China.

Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women, and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. In this study, we showed that compared to healthy controls, hepatic ACSL4 levels in NAFLD patients were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β-oxidation of fatty acids and to minimize lipid accumulation by up-regulating PGC1α. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, low-dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.
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http://dx.doi.org/10.1002/hep.32148DOI Listing
September 2021

Circ-PGC increases the expression of FOXR2 by targeting miR-532-3p to promote the development of non-small cell lung cancer.

Cell Cycle 2021 Sep 8:1-15. Epub 2021 Sep 8.

Department of Cardiothoracic Surgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China.

This study was to explore the function of circular progastricsin (circ-PGC) in NSCLC. The histological morphology of tumor tissues was observed by hematoxylin and eosin (HE) staining. The expression of circ-PGC, miR-532-3p and forkhead box R2 (FOXR2) mRNA was measured by real-time quantitative polymerase chain reaction (RT-qPCR). The protein level of FOXR2 was checked by western blot. In functional analyses, cell viability, colony formation, cell apoptosis, cell migration and cell invasion were investigated using cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry assay, wound healing assay and transwell assay. Besides, glycolysis metabolism was assessed by the levels of glucose consumption, lactate production and adenosine triphosphate (ATP) production. The predicted relationship between miR-532-3p and circ-PGC and FOXR2 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The results showed that circ-PGC and FOXR2 were upregulated in NSCLC tissues and cells. Circ-PGC knockdown or FOXR2 knockdown inhibited NSCLC cell viability, colony formation, cell migration, invasion and glycolysis metabolism, and FOXR2 overexpression rescued these inhibitory effects caused by circ-PGC knockdown. MiR-532-3p harbored the same binding site with circ-PGC and FOXR2, and circ-PGC positively regulated FOXR2 expression by targeting miR-532-3p. The expression of β-catenin and c-Myc was decreased in cells after circ-PGC knockdown but recovered with miR-532-3p inhibition or FOXR2 overexpression. Circ-PGC downregulation also inhibited tumor growth . In conclusion, circ-PGC positively regulated FOXR2 expression by competitively binding to miR-532-3p, thereby promoting the development of NSCLC, and the Wnt/β-catenin signaling pathway might be activated by the circ-PGC/miR-532-3p/FOXR2 network.
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http://dx.doi.org/10.1080/15384101.2021.1974788DOI Listing
September 2021

PSPC1 regulates CHK1 phosphorylation through phase separation and participates in mouse oocyte maturation.

Acta Biochim Biophys Sin (Shanghai) 2021 Sep 7. Epub 2021 Sep 7.

Hubei Provincial Key Laboratory of Developmentally Originated Disease, Department of Tissue and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan 430062, China.

Liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in mammal cells. However, there are few reports that focus on the correlation of mouse oocyte maturation with LLPS. Previous studies have reported that paraspeckle component 1 (PSPC1) is related to the occurrence and development of tumors, but whether PSPC1 functions in mouse oocyte maturation is still unclear. Sequence analysis of PSPC1 protein showed that it contains a prion-like domain (PrLD) that is required for phase separation of proteins. In this study, we found that PSPC1 could undergo phase separation. Moreover, the loss of PrLD domain of PSPC1 could greatly weaken its phase separation ability. The immunofluorescence assays showed that PSPC1 is present in mouse oocytes in the germinal vesicle (GV) stage. Knockdown of PSPC1 significantly impeded the maturation of mouse oocytes in vitro. CHK1 has been reported to play important roles in the GV stage of mouse oocytes. Co-IP experiment revealed that PSPC1 could interact with phosphatase serine/threonine-protein phosphatase 5 (PPP5C), which regulates CHK1 phosphorylation. Western blot analysis revealed that PSPC1 could regulate the phosphorylation of CHK1 through PPP5C; however, PSPC1 without PrLD domain was inactive, suggesting that the lack of phase separation ability led to the abnormal function of PSPC1 in regulating CHK1 phosphorylation. Thus, we conclude that PSPC1 may undergo phase separation to regulate the phosphorylation level of CHK1 via PPP5C and participate in mouse oocyte maturation. Our study provides new insights into the mechanism of mouse oocyte maturation.
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http://dx.doi.org/10.1093/abbs/gmab123DOI Listing
September 2021

Development of fruit color in Rubus chingii Hu (Chinese raspberry): A story about novel offshoots of anthocyanin and carotenoid biosynthesis.

Plant Sci 2021 Oct 21;311:110996. Epub 2021 Jul 21.

South Oak, Stuttgart, AR, 72160, USA.

Rubus chingii, is widely distributed in many Asian countries and well known for its medicinal and dietary properties. Diversity of fruit color in raspberry has been attributed to the presence of either anthocyanins or carotenoids. In this study, we investigated anthocyanins and carotenoids, and their biosynthesis by LC-MS/MS. Six anthocyanins mainly consisted of flavanol-anthocyanins while five carotenoids mainly consisted of β-citraurin esters. Flavanol-anthocyanins were produced from an offshoot of the anthocyanin biosynthesis, which started with biosynthesis of flavanols and anthocyanidin by leucoanthocyanidin reductase (LAR)/anthocyanidin reductase (ANR) and anthocyanidin synthase (ANS/LDOX) respectively. β-citraurin esters were produced from cleavage of zeaxanthin and esterification by organic acid, which was an offshoot of the carotenoid biosynthesis. The offshoot started with biosynthesis of zeaxanthin and β-citraurin by carotene β-hydroxylase (CHYB/LUT5) and carotenoid cleavage dioxygenase (CCD) respectively. During fruit ripening, biosynthesis of flavanols and anthocyanins was down-regulated by genes/proteins involved in phenylpropanoid and flavonoid biosynthesis, while biosynthesis of β-citraurin esters was up-regulated by imbalanced expression of genes/proteins involved in β,β-ring and β, ε-ring hydroxylation. Thus, β-citraurin esters, instead of anthocyanins imparted reddish color to the ripe fruit. These pigments and their biosynthesis in R. chingii are totally different from what occurs in other raspberry species.
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http://dx.doi.org/10.1016/j.plantsci.2021.110996DOI Listing
October 2021

Differential metabolism-associated gene expression of duck pancreatic cells in response to two strains of duck hepatitis A virus type 1.

Arch Virol 2021 Sep 5. Epub 2021 Sep 5.

Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou, 350013, Fujian, People's Republic of China.

Several outbreaks of duck hepatitis A virus type 1 (DHAV-1), which were characterized by yellow coloration and hemorrhage in pancreatic tissues, have occurred in China. The causative agent is called pancreatitis-associated DHAV-1. The mechanisms involved in pancreatitis-associated DHAV-1 infection are still unclear. Transcriptome analysis of duck pancreas infected with classical-type DHAV-1 and pancreatitis-associated DHAV-1 was carried out. Deep sequencing with Illumina-Solexa resulted in a total of 53.9 Gb of clean data from the cDNA library of the pancreas, and a total of 29,597 unigenes with an average length of 993.43 bp were generated by de novo sequence assembly. The expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase, which are involved in glycine, serine, and threonine metabolism pathways, were significantly downregulated in ducks infected with pancreatitis-associated DHAV-1 compared with those infected with classical-type DHAV-1. These findings provide information regarding differences in expression levels of metabolism-associated genes between ducks infected with pancreatitis-associated DHAV-1 and those infected with classical-type DHAV-1, indicating that intensive metabolism disorders may contribute to the different phenotypes of DHAV-1-infection.
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http://dx.doi.org/10.1007/s00705-021-05199-4DOI Listing
September 2021

The Current Role of Clevidipine in the Management of Hypertension.

Am J Cardiovasc Drugs 2021 Sep 2. Epub 2021 Sep 2.

College of Pharmacy, University of South China, No. 28, Changsheng West Road, Zhengxiang District, Hengyang, 421001, Hunan, China.

Acute hypertension, which may damage blood vessels, causes irreversible organ damage to the vasculature, central nervous system, kidney, and heart. Clevidipine, the first third-generation calcium channel antagonist approved by the Food and Drug Administration (FDA) in the past 20 years, is an ultra-short-acting calcium channel blocker that inhibits L-type calcium channels with high clearance and low distribution, can be rapidly metabolized into the corresponding inactive acid, and is rapidly hydrolyzed into inactive metabolites by esterase in arterial blood. Clevidipine is the same as nicardipine in that the main physiological effect is vasodilation and the main target is the arterial system, which has a limited effect on capacitor vessels. Unlike nitroglycerin, clevidipine has a limited effect on preload. In contrast to other direct-acting vasodilators, clevidipine has an ultra-short half-life due to metabolism by nonspecific blood and tissue esterases. Clevidipine trials conducted in adult populations have proven that it can rapidly control blood pressure in cardiac surgery situations and that adverse reactions to clevidipine are similar to those with other antihypertensive agents. In recent years, clinical trials have shown that clevidipine has excellent blood pressure-lowering capability in patients with acute neurological injury (hemorrhage, stroke, and subarachnoid and acute intracerebral hemorrhage), those  undergoing coronary artery bypass graft or spinal surgery, and in those with cerebral aneurysm/pheochromocytoma, acute heart failure, acute aortic syndromes, or renal insufficiency with severe hypertension, and it is equivalent to commonly used blood pressure-lowering medicines such as nicardipine or nitroglycerin. However, there is a lack of large-scale clinical trial data on the efficacy and safety of clevidipine in children during the perioperative period.
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http://dx.doi.org/10.1007/s40256-021-00494-6DOI Listing
September 2021

Chemiluminescence Immunoassay Based Serological Immunoassays for Detection of SARS-CoV-2 Neutralizing Antibodies in COVID-19 Convalescent Patients and Vaccinated Population.

Viruses 2021 07 30;13(8). Epub 2021 Jul 30.

State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

The development of rapid serological detection methods re urgently needed for determination of neutralizing antibodies in sera. In this study, four rapid methods (ACE2-RBD inhibition assay, S1-IgG detection, RBD-IgG detection, and N-IgG detection) were established and evaluated based on chemiluminescence technology. For the first time, a broadly neutralizing antibody with high affinity was used as a standard for the quantitative detection of SARS-CoV-2 specific neutralizing antibodies in human sera. Sera from COVID-19 convalescent patients (N = 119), vaccinated donors (N = 86), and healthy donors (N = 299) confirmed by microneutralization test (MNT) were used to evaluate the above methods. The result showed that the ACE2-RBD inhibition assay calculated with either ACE2-RBD binding inhibition percentage rate or ACE2-RBD inhibiting antibody concentration were strongly correlated with MNT (r ≥ 0.78, < 0.0001) and also highly consistent with MNT (Kappa Value ≥ 0.94, < 0.01). There was also a strong correlation between the two evaluation indices (r ≥ 0.99, < 0.0001). Meanwhile, S1-IgG and RBD-IgG quantitative detection were also significantly correlated with MNT (r ≥ 0.73, < 0.0001), and both methods were highly correlated with each other (r ≥ 0.95, < 0.0001). However, the concentration of N-IgG antibodies showed a lower correlation with the MNT results (r < 0.49, < 0.0001). The diagnostic assays presented here could be used for the evaluation of SARS-CoV-2 vaccine immunization effect and serological diagnosis of COVID-19 patients, and could also have guiding significance for establishing other rapid serological methods to surrogate neutralization tests for SARS-CoV-2.
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http://dx.doi.org/10.3390/v13081508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402865PMC
July 2021

Transcriptomic, Proteomic and Metabolomic Analysis of Flavonoid Biosynthesis During Fruit Maturation in .

Front Plant Sci 2021 10;12:706667. Epub 2021 Aug 10.

Independent Researcher, Stuttgart, AR, United States.

HU, is a medicinal and nutritious fruit, which is very rich in flavonoids. However, the biosynthesis of its flavonoids is poorly understood. This study examined flavonoids and the genes/proteins at four fruit ripening phases using LC-MS/MS and qPCR. Six major kinds of anthocyanins, primarily consisted of flavanol-anthocyanins, which differed in form or concentration from other species. In contrast to other known raspberries species, had a decline in flavonoids during fruit ripening, which was due to down-regulation of genes and proteins involved in phenylpropanoid and flavonoid biosynthesis. Unexpectedly, anthocyanin also continuously decreased during fruit maturation. This suggests that anthocyanins are not responsible for the fruit's reddish coloration. Flavanol-anthocyanins were derived from the proanthocyanidin pathway, which consumed two flavonoid units both produced through the same upstream pathway. Their presence indicates a reduction in the potential biosynthesis of anthocyanin production. Also, the constantly low expression of RchANS gene resulted in low levels of anthocyanin biosynthesis. The lack of RchF3'5'H gene/protein hindered the production of delphinidin glycosides. Flavonoids primarily comprising of quercetin/kaempferol-glycosides were predominately located at fruit epidermal-hair and placentae. The proportion of receptacle/drupelets changes with the maturity of the fruit and may be related to a decrease in the content of flavonoids per unit mass as the fruit matures. The profile and biosynthesis of flavonoids are unique to . The unique flavonol pathways of could be used to broaden the genetic diversity of raspberry cultivars and to improve their fruit quality.
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http://dx.doi.org/10.3389/fpls.2021.706667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384110PMC
August 2021

SYMPK Is Required for Meiosis and Involved in Alternative Splicing in Male Germ Cells.

Front Cell Dev Biol 2021 9;9:715733. Epub 2021 Aug 9.

Department of Tissue and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.

SYMPK is a scaffold protein that supports polyadenylation machinery assembly on nascent transcripts and is also involved in alternative splicing in some mammalian somatic cells. However, the role of SYMPK in germ cells remains unknown. Here, we report that SYMPK is highly expressed in male germ cells, and germ cell-specific knockout (cKO) of in mouse leads to male infertility. cKO mice showed reduced spermatogonia at P4 and almost no germ cells at P18. cKO spermatocytes exhibit defects in homologous chromosome synapsis, DNA double-strand break (DSB) repair, and meiotic recombination. RNA-Seq analyses reveal that SYMPK is associated with alternative splicing, besides regulating the expressions of many genes in spermatogenic cells. Importantly, deletion results in abnormal alternative splicing and a decreased expression of . Taken together, our results demonstrate that SYMPK is pivotal for meiotic progression by regulating pre-mRNA alternative splicing in male germ cells.
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http://dx.doi.org/10.3389/fcell.2021.715733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380814PMC
August 2021

Dupilumab Demonstrates Rapid and Consistent Improvement in Extent and Signs of Atopic Dermatitis Across All Anatomical Regions in Pediatric Patients 6 Years of Age and Older.

Dermatol Ther (Heidelb) 2021 08 24. Epub 2021 Aug 24.

Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA.

Introduction: In phase III trials in adolescents and children with atopic dermatitis (AD), dupilumab significantly decreased global disease severity. However, the effects of dupilumab on the extent and signs of AD across different anatomical regions were not reported. Here we characterize the efficacy of dupilumab in improving the extent and signs of AD across four different anatomical regions in children and adolescents.

Methods: A post hoc subset analysis was performed using data from two randomized, double-blind, placebo-controlled, international multicenter, phase III trials of dupilumab therapy in adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD and children aged ≥ 6 to < 12 years with severe AD. Endpoints included mean percentage change in Eczema Area and Severity Index (EASI) signs (erythema, edema/papulation, excoriation, lichenification) and extent of AD (measured by percentage of body surface area [% BSA] involvement) from baseline to week 16 across four anatomical regions (head and neck, trunk, upper extremities, lower extremities).

Results: Dupilumab improved both the extent and severity of AD signs across the four anatomical regions. Improvements were shown to be similar across the four anatomical regions for % BSA involvement and for reduction in EASI signs. Improvements in all signs were seen early, within the first 4 weeks of treatment, and were sustained through week 16, across all regions.

Conclusions: In pediatric patients 6 years of age and older, treatment with dupilumab resulted in rapid and consistent improvement in the extent and signs of AD across all anatomical regions. CLINICALTRIALS.

Gov Identifiers: LIBERTY AD ADOL (NCT03054428) and LIBERTY AD PEDS (NCT03345914). Does dupilumab provide improvement in atopic dermatitis across all anatomical regions in children and adolescents? (MP4 48,385 kb).
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http://dx.doi.org/10.1007/s13555-021-00568-yDOI Listing
August 2021

Puerarin Inhibits Ferroptosis and Inflammation of Lung Injury Caused by Sepsis in LPS Induced Lung Epithelial Cells.

Front Pediatr 2021 4;9:706327. Epub 2021 Aug 4.

Department of Pediatrics, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, China.

Ferroptosis is a new type of programmed cell death, which plays an important role in lung injury caused by sepsis. Studies have reported that Puerarin (Pue) can treat lung injury caused by sepsis in children, but whether it plays a role by regulating iron death has not been reported. LPS induced human alveolar epithelial cell A549 to form a model of lung injury caused by sepsis. MTT detected the effect of Pue on A549 cell viability and the effect of Pue on LPS-induced A549 cell viability. The effects of Pue on LPS-induced inflammatory cytokines TNF-α, IL-8, IL-1β in A549 cells were determined by ELISA assay. The expression level of MDA was detected by TBARS colorimetric quantitative detection kit. GSH kit was used to detect the expression of GSH in cells. The iron kit detected the total iron level and the expression level of ferric divalent ions in the cells. DCFH-DA fluorescent probe was used to detect ROS levels. Western blot was used to detect the expression of ferroptosis-related proteins in cells. Pue alleviated LPS-induced injury and inflammatory response in A549 cells, and Pue reduced the expression of ROS, MDA and GSH in LPS-induced A549 cells. In addition, Pue reduced total iron levels and ferrous ion levels in LPS-induced A549 cells, and decreased the expression of iron ferroptosis-related proteins. Puerarin inhibited ferroptosis and inflammation of lung injury caused by sepsis in children in LPS induced lung epithelial cells.
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http://dx.doi.org/10.3389/fped.2021.706327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371381PMC
August 2021

Retraction Note to: Deoxynivalenol-induced alterations in the redox status of HepG2 cells: identification of lipid hydroperoxides, the role of Nrf2-Keap1 signaling, and protective effects of zinc.

Mycotoxin Res 2021 Aug 20. Epub 2021 Aug 20.

Laboratory for Advanced Lipid Analysis, Faculty of Health Sciences, Hokkaido University, Kita 12, Nishi 5, Sapporo, Japan.

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http://dx.doi.org/10.1007/s12550-021-00440-0DOI Listing
August 2021

Application of Pet-CT Fusion Deep Learning Imaging in Precise Radiotherapy of Thyroid Cancer.

J Healthc Eng 2021 5;2021:2456429. Epub 2021 Aug 5.

Nuclear Medicine Department, The First Hospital of Jilin University, Changchun 130000, Jilin, China.

This article explores the value of wall F-FDG PET/Cr imaging in the diagnosis of thyroid cancer, studies its ability to distinguish benign and malignant thyroid lesions, and seeks ways to improve the accuracy of diagnosis. The normal control group selected 40 patients who came to our center for physical examination. In the normal control group, the average value of the standard uptake value of both sides of the thyroid was used as the SUV of the thyroid gland and the highest SUV value of the patient's lesion (SUV max) represented the SUV of the lesion. After injection of imaging agent 18F-FD1G, routine imaging was performed at 1h, time-lapse imaging was performed at 2.5 h, and the changes with conventional imaging were compared to infer the benign and malignant lesions. We used SPSS software to carry out statistical analysis, respectively, carrying out analysis of variance, paired -test, independent sample -test, and linear correlation analysis. In the thyroid cancer group, 87.5% of the delayed imaging SUV was higher than the conventional imaging SUV, while 83.33% of the benign disease group had a lower SUV than the conventional imaging SUV. 18F-FDG PET/CT imaging has higher sensitivity and specificity for the diagnosis of recurrence or metastasis in patients with Tg positive. However, it has lower sensitivity and specificity for the diagnosis of 131I-Dx-WBS negative DTC and 18F-FDG PET/CT. The specificity increases with the increase of serum Tg level. The above results confirm that 18F-FDG PET/CT imaging is of great significance for the diagnosis of recurrence or metastasis in patients; with PET/CT imaging, the results changed 16.13% of the Tg-positive and 131I-Dx-WBS negative DTC patients' later treatment decision. The decision-making and curative effect evaluation have certain value.
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http://dx.doi.org/10.1155/2021/2456429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370813PMC
August 2021

Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis.

J Immunother Cancer 2021 Aug;9(8)

Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: To provide pooled longer term data from three groups of a phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), and to determine duration of response (DOR) and impact on quality of life (QoL).

Methods: Patients received cemiplimab 3 mg/kg every 2 weeks (group 1, metastatic CSCC [mCSCC], n=59; group 2, locally advanced CSCC, n=78) or cemiplimab 350 mg every 3 weeks (group 3, mCSCC, n=56). Primary endpoint was objective response rate (ORR) per independent central review (ICR). QoL was repeatedly measured at day 1 of each treatment cycle (groups 1 and 2: 8 weeks; group 3: 9 weeks).

Results: Median duration of follow-up was 15.7 months. Overall, ORR per ICR was 46.1% (95% CI: 38.9% to 53.4%). Complete response (CR) rates were 20.3%, 12.8%, and 16.1% for groups 1, 2, and 3, respectively. Median time to CR was 11.2 months. Among patients with partial response or CR, the estimated proportion of patients with ongoing response at 12 months from the first objective response was 87.8% (95% CI: 78.5% to 93.3%), with median DOR not reached. Kaplan-Meier estimated probability of overall survival (OS) was 73.3% (95% CI: 66.1% to 79.2%) at 24 months, with median OS not reached. Global Health Status (GHS)/QoL improvements were observed as early as cycle 2 and were significantly improved and durable until last assessment. Kaplan-Meier estimate of median time to first clinically meaningful improvement for pain was 2.1 (95% CI: 2.0 to 3.7) months and was significantly improved in responders versus non-responders (p<0.0001).

Conclusions: This is the largest (n=193) clinical dataset for a programmed cell death-1 inhibitor against advanced CSCC, confirming the sustained substantial clinical activity of cemiplimab in these patients, including new findings of improved CR rates over time, increasing DOR, and durable pain control and GHS/QoL improvement.

Trial Registration Number: ClinicalTrials.gov Registry (NCT02760498), https://clinicaltrialsgov/ct2/show/NCT02760498.
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http://dx.doi.org/10.1136/jitc-2021-002757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382148PMC
August 2021

Prediction of Genetic Factors of Hyperthyroidism Based on Gene Interaction Network.

Front Cell Dev Biol 2021 2;9:700355. Epub 2021 Aug 2.

Department of Thyroid Surgery, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.

The number of hyperthyroidism patients is increasing these years. As a disease that can lead to cardiovascular disease, it brings great potential health risks to humans. Since hyperthyroidism can induce the occurrence of many diseases, studying its genetic factors will promote the early diagnosis and treatment of hyperthyroidism and its related diseases. Previous studies have used genome-wide association analysis (GWAS) to identify genes related to hyperthyroidism. However, these studies only identify significant sites related to the disease from a statistical point of view and ignore the complex regulation relationship between genes. In addition, mutation is not the only genetic factor of causing hyperthyroidism. Identifying hyperthyroidism-related genes from gene interactions would help researchers discover the disease mechanism. In this paper, we purposed a novel machine learning method for identifying hyperthyroidism-related genes based on gene interaction network. The method, which is called "RW-RVM," is a combination of Random Walk (RW) and Relevance Vector Machines (RVM). RW was implemented to encode the gene interaction network. The features of genes were the regulation relationship between genes and non-coding RNAs. Finally, multiple RVMs were applied to identify hyperthyroidism-related genes. The result of 10-cross validation shows that the area under the receiver operating characteristic curve (AUC) of our method reached 0.9, and area under the precision-recall curve (AUPR) was 0.87. Seventy-eight novel genes were found to be related to hyperthyroidism. We investigated two genes of these novel genes with existing literature, which proved the accuracy of our result and method.
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http://dx.doi.org/10.3389/fcell.2021.700355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365469PMC
August 2021

Hepatic interferon regulatory factor 8 expression mediates liver ischemia/reperfusion injury in mice.

Biochem Pharmacol 2021 Aug 13;192:114728. Epub 2021 Aug 13.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. Electronic address:

Hepatic ischemia/reperfusion (I/R) injury is an inevitable complication of hepatic surgery occasioned by liver transplantation and resection. The progression from liver ischemia to reperfusion injury is accompanied by abnormal metabolism, Kupffer cell activation, neutrophil recruitment and the release of cytokines. Activation of several interferon regulatory factors (IRFs) has been reported to either enhance or restrict I/R progression, but the role of IRF8 in the regulation of I/R injury progression is still unknown. In this study, we explore the IRF8 function in the I/R-mediated liver injury using overexpressed hepatic IRF8 and knockout mice. According to our results, IRF8 knockout mice had significantly lower inflammatory cells infiltration, inflammatory cytokines release and serum aspartate aminotransferase/alanine aminotransferase levels that improved the necrotic injury after I/R, unlike the control mice. Conversely, the overexpression of IRF8 in WT mice markedly aggravated the liver structure damage and its abnormal function. We further showed that IRF8-mediated inflammatory cells infiltration were partly dependent on early autophagy and NF-κΒ signal pathway during I/R. AAV8-IRF8-I/R mice pretreated with autophagy inhibitor hydroxychloroquine and NF-κΒ signal pathway inhibitor secukinumab could drastically reverse the IRF8-mediated increase of neutrophil infiltration and chemokine release at different degrees. This work uncovered a critical role of IRF8 in the modulation of the hepatic microenvironment and as a potential target in the initial treatment of I/R injury.
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http://dx.doi.org/10.1016/j.bcp.2021.114728DOI Listing
August 2021

The potential value of microRNA-145 for predicting prognosis in patients with ovarian cancer: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Aug;100(32):e26922

Department of Gynecology, Hainan Western Central Hospital, Danzhou, Hainan Province, China.

Background: As an anticancer gene, microRNA-145 (miRNA-145) inhibits the growth, migration, and invasion of cancer cells, and inhibits tumorigenesis by targeting various genes that are abnormally expressed in tumors. However, whether miRNA-145 can be applied as a biomarker for potential prognosis of ovarian cancer still remains controversial. Therefore, this study further explored the prognostic value and mechanism of miRNA-145 in ovarian cancer through meta-analysis and bioinformatics analysis.

Methods: Eligible studies were identified by searching the China National Knowledge Infrastructure, Chinese Biomedical literature Database, Chinese Scientific and Journal Database, Wan Fang database, PubMed, EMBASE, and Web of Science up to July 2021. Pooled hazard ratios with 95% confidence intervals for patient survival were calculated to investigate the effects of miRNA-145 on the prognosis of ovarian cancer. Survival curves of differential expression of miRNA-145 were analyzed by Oncomir. The target genes of miRNA-145 were predicted by miRTARbase and Diana-Tarbase V7.0 database. Enrichr database was applied to analyze the target genes by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Protein-protein interaction network of target genes was constructed from STRING database. Cytoscape software was used to screen the hub genes to meet the requirements. The Gene Expression Profiling Interactive Analysis database was applied to analyze the survival outcomes of hub genes.

Results: The results of this meta-analysis would be submitted to peer-reviewed journals for publication.

Conclusion: This study provides high-quality evidence to support the relationship between miRNA-145 expression and ovarian cancer prognosis. Through bioinformatics analysis, we further explored the mechanism of miRNA-145 in ovarian cancer and related pathways.
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http://dx.doi.org/10.1097/MD.0000000000026922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360411PMC
August 2021

Silencing of AHNAK2 restricts thyroid carcinoma progression by inhibiting the Wnt/β-catenin pathway.

Neoplasma 2021 Aug 11. Epub 2021 Aug 11.

Nuclear Medicine Department, The First Hospital of Jilin University, Changchun, China.

AHNAK nucleoprotein 2 (AHNAK2) has been proposed to have an oncogenic role in various human cancers. However, the functional role of AHNAK2 in thyroid carcinoma (TC) progression has never been explored. In this study, quantitative real-time polymerase chain reaction and western blot were conducted to evaluate the expression of genes. The functional role of AHNAK2 was elucidated by cell count kit-8, colony-forming assay, wound healing assay, and Transwell invasion assay. We found that AHNAK2 was highly expressed in thyroid carcinoma, and it was tightly correlated with the pathological stage in TC. The mRNA and protein levels of AHNAK2 were increased in TC cells. Silencing of AHNAK2 restricted the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of TC cells. AHNAK2 silencing inhibited the protein expression of β-catenin and cyclin D1, and AHNAK2 overexpression had the opposite effects. Moreover, LiCl or ICG-001 exposure counteracted the effects of AHNAK2 silencing or upregulation on malignant phenotypes of TC cells. In conclusion, the knockdown of AHNAK2 restrained the proliferation, metastasis, and EMT of TC cells by inhibiting the Wnt/β-catenin pathway, providing a new potential mechanism of AHNAK2 in understanding the oncogenesis and progression of TC.
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http://dx.doi.org/10.4149/neo_2021_210304N276DOI Listing
August 2021

Treatment-induced arteriolar revascularization and miR-126 enhancement in bone marrow niche protect leukemic stem cells in AML.

J Hematol Oncol 2021 08 9;14(1):122. Epub 2021 Aug 9.

Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, 1500 E Duarte Road, Duarte, CA, 91010, USA.

Background: During acute myeloid leukemia (AML) growth, the bone marrow (BM) niche acquires significant vascular changes that can be offset by therapeutic blast cytoreduction. The molecular mechanisms of this vascular plasticity remain to be fully elucidated. Herein, we report on the changes that occur in the vascular compartment of the FLT3-ITD+ AML BM niche pre and post treatment and their impact on leukemic stem cells (LSCs).

Methods: BM vasculature was evaluated in FLT3-ITD+ AML models (Mll/Flt3 mouse and patient-derived xenograft) by 3D confocal imaging of long bones, calvarium vascular permeability assays, and flow cytometry analysis. Cytokine levels were measured by Luminex assay and miR-126 levels evaluated by Q-RT-PCR and miRNA staining. Wild-type (wt) and Mll/Flt3 mice with endothelial cell (EC) miR-126 knockout or overexpression served as controls. The impact of treatment-induced BM vascular changes on LSC activity was evaluated by secondary transplantation of BM cells after administration of tyrosine kinase inhibitors (TKIs) to Mll/Flt3 mice with/without either EC miR-126 KO or co-treatment with tumor necrosis factor alpha (TNFα) or anti-miR-126 miRisten.

Results: In the normal BM niche, CD31Sca-1 ECs lining arterioles have miR-126 levels higher than CD31Sca-1 ECs lining sinusoids. We noted that during FLT3-ITD+ AML growth, the BM niche lost arterioles and gained sinusoids. These changes were mediated by TNFα, a cytokine produced by AML blasts, which induced EC miR-126 downregulation and caused depletion of CD31Sca-1 ECs and gain in CD31Sca-1 ECs. Loss of miR-126 ECs led to a decreased EC miR-126 supply to LSCs, which then entered the cell cycle and promoted leukemia growth. Accordingly, antileukemic treatment with TKI decreased the BM blast-produced TNFα and increased miR-126 ECs and the EC miR-126 supply to LSCs. High miR-126 levels safeguarded LSCs, as shown by more severe disease in secondary transplanted mice. Conversely, EC miR-126 deprivation via genetic or pharmacological EC miR-126 knock-down prevented treatment-induced BM miR-126 EC expansion and in turn LSC protection.

Conclusions: Treatment-induced CD31Sca-1 EC re-vascularization of the leukemic BM niche may represent a LSC extrinsic mechanism of treatment resistance that can be overcome with therapeutic EC miR-126 deprivation.
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http://dx.doi.org/10.1186/s13045-021-01133-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351342PMC
August 2021

miRNAomics analysis reveals the promoting effects of cigarette smoke extract-treated Beas-2B-derived exosomes on macrophage polarization.

Biochem Biophys Res Commun 2021 Oct 5;572:157-163. Epub 2021 Aug 5.

Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-marketed TCM, State Key Laboratory of Biocontrol and Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China. Electronic address:

Inhalation of cigarette smoke induces airway and parenchyma inflammation that predisposes smokers to multiple lung diseases such as COPD. Macrophage polarization, an important specifying feature of inflammation, is involved in the progression of pulmonary inflammation. Exosomes and their loaded miRNAs provide a medium for cross-talk between alveolar macrophages and lung epithelial cells to maintain lung homeostasis. In this study, we treated Beas-2B with CSE to speculate the effects of Beas-2B-derived exosomes on macrophage polarization and performed exosomal miRNAomics analysis to explore the mechanism. We found that CSE-treated Beas-2B-derived exosomes could not only increase the percentages of CD86, CD80 CD163, and CD206 cells but also induce the secretion of TNF-α, IL-6, iNOS, IL-10, Arg-1, and TGF-β, indicating both M1 and M2 polarization of RAW264.7 macrophages were promoting. We performed miRNAomics analysis to identify 27 differentially expressed exosomal miRNAs such as miR-29a-3p and miR-1307-5p. Next, we obtained 14942 target genes of these miRNAs such as SCN1A and PLEKHA1 through the prediction of TargetScan and miRanda. We utilized KEGG enrichment analysis for these targets to identify potential pathways such as the PI3K-Akt signaling pathway and the MAPK signaling pathway on the regulation of macrophage polarization. We further found that miR-21-3p or miR-27b-3p may play critical roles in the promotion of CSE-Exo on macrophage polarization by miRNA interference. Collectively, this study provided novel information for diagnostic and therapeutic tactics of cigarette smoke-related lung diseases.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.093DOI Listing
October 2021

Effect of Laser Energy Density on the Microstructure and Texture Evolution of Hastelloy-X Alloy Fabricated by Laser Powder Bed Fusion.

Materials (Basel) 2021 Jul 31;14(15). Epub 2021 Jul 31.

State key Laboratory of Manufacturing System Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

It is of great importance to study the microstructure and textural evolution of laser powder bed fusion (LPBF) formed Hastelloy-X alloys, in order to establish a close relationship between the process, microstructure, and properties through the regulation of the Hastelloy-X formation process parameters. In this paper, components of a Hastelloy-X alloy were formed with different laser energy densities (also known as the volume energy density VED). The densification mechanism of Hastelloy-X was studied, and the causes of defects, such as pores and cracks, were analyzed. The influence of different energy densities on grain size, texture, and orientation was investigated using an electron backscatter diffraction technique. The results show that the average grain size, primary dendrite arm spacing, and number of low angle grain boundaries increased with the increase of energy density. At the same time, the VED can strengthen the texture. The textural intensity increases with the increase of energy density. The best mechanical properties were obtained at the VED of 96 J·mm.
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http://dx.doi.org/10.3390/ma14154305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347165PMC
July 2021

Effects of Virtual Reality Intervention on Neural Plasticity in Stroke Rehabilitation: A Systematic Review.

Arch Phys Med Rehabil 2021 Aug 2. Epub 2021 Aug 2.

Division of Physical Therapy Education, College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE. Electronic address:

Objective: To systematically review and examine the current literature regarding the effects of virtual reality (VR)-based rehabilitation on neural plasticity changes in survivors of stroke.

Data Sources: We searched 6 bioscience and engineering databases, including Medline via EBSCO, Embase, PsycINFO, IEEE Explore, Cumulative Index of Nursing and Allied Health, and Scopus.

Study Selection: We selected studies reporting on the pre-post assessment of a VR intervention with neural plasticity measures published between 2000 and 2021.

Data Extraction: Two independent reviewers conducted study selection, data extraction, and quality assessment. They assessed methodological quality of controlled trials using the Physiotherapy Evidence Database scale and evaluated risk of bias of pre-post intervention and case studies using the National Institutes of Health Quality Assessment Tool.

Data Synthesis: We included 27 studies (n=232). We rated 7 randomized-controlled trials as good quality and 2 clinical-controlled trials as moderate. Based on the risk of bias assessment, we graded 1 pre-post study and 1 case study as good quality, 1 pre-post study and 1 case study as poor, and the other 14 studies as fair. After the VR intervention, main neurophysiological findings across studies include: (1) improved interhemispheric balance; (2) enhanced cortical connectivity; (3) increased cortical mapping of the affected limb muscles; (4) the improved neural plasticity measures were correlated to the enhanced behavior outcomes; (5) increased activation of regions in frontal cortex; and (6) the mirror neuron system may be involved.

Conclusions: VR-induced changes in neural plasticity for survivors of stroke. Positive correlations between the neural plasticity changes and functional recovery elucidates the mechanisms of VR-based therapeutic effects in stroke rehabilitation. This review prompts systematic understanding of the neurophysiological mechanisms of VR-based stroke rehabilitation and summarizes the emerging evidence for ongoing innovation of VR systems and application in stroke rehabilitation.
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http://dx.doi.org/10.1016/j.apmr.2021.06.024DOI Listing
August 2021

Immune-mediated uveitis and lifestyle factors: A review.

Ophthalmic Res 2021 Jul 26. Epub 2021 Jul 26.

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http://dx.doi.org/10.1159/000518496DOI Listing
July 2021

Revealing protein-protein interactions at the transcriptome scale by sequencing.

Mol Cell 2021 Jul 27. Epub 2021 Jul 27.

Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:

We describe PROPER-seq (protein-protein interaction sequencing) to map protein-protein interactions (PPIs) en masse. PROPER-seq first converts transcriptomes of input cells into RNA-barcoded protein libraries, in which all interacting protein pairs are captured through nucleotide barcode ligation, recorded as chimeric DNA sequences, and decoded at once by sequencing and mapping. We applied PROPER-seq to human embryonic kidney cells, T lymphocytes, and endothelial cells and identified 210,518 human PPIs (collected in the PROPER v.1.0 database). Among these, 1,365 and 2,480 PPIs are supported by published co-immunoprecipitation (coIP) and affinity purification-mass spectrometry (AP-MS) data, 17,638 PPIs are predicted by the prePPI algorithm without previous experimental validation, and 100 PPIs overlap human synthetic lethal gene pairs. In addition, four previously uncharacterized interaction partners with poly(ADP-ribose) polymerase 1 (PARP1) (a critical protein in DNA repair) known as XPO1, MATR3, IPO5, and LEO1 are validated in vivo. PROPER-seq presents a time-effective technology to map PPIs at the transcriptome scale, and PROPER v.1.0 provides a rich resource for studying PPIs.
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http://dx.doi.org/10.1016/j.molcel.2021.07.006DOI Listing
July 2021

Combined transcriptomic and metabolic analyses reveal potential mechanism for fruit development and quality control of Chinese raspberry (Rubus chingii Hu).

Plant Cell Rep 2021 Jul 31. Epub 2021 Jul 31.

School of Pharmaceutical, Chemical and Materials Engineering, Taizhou University, Taizhou, 318000, People's Republic of China.

Key Message: Combined transcriptomic and metabolic analyses reveal that fruit of Rubus chingii Hu launches biosynthesis of phenolic acids and flavonols at beginning of fruit set and then coordinately accumulated or converted to their derivatives. Rubus chingii Hu (Chinese raspberry) is an important dual functional food with nutraceutical and pharmaceutical values. Comprehensively understanding the mechanisms of fruit development and bioactive components synthesis and regulation could accelerate genetic analysis and molecular breeding for the unique species. Combined transcriptomic and metabolic analyses of R. chingii fruits from different developmental stages, including big green, green-to-yellow, yellow-to-orange, and red stages, were conducted. A total of 89,188 unigenes were generated and 57,545 unigenes (64.52%) were annotated. Differential expression genes (DEGs) and differentially accumulated metabolites (DAMs) were mainly involved in the biosynthesis of secondary metabolites. The fruit launched the biosynthesis of phenolic acids and flavonols at the very beginning of fruit set and then coordinately accumulated or converted to their derivatives. This was tightly regulated by expressions of the related genes and MYB and bHLH transcription factors. The core genes products participated in the biosynthesis of ellagic acid (EA) and kaempferol-3-O-rutinoside (K-3-R), such as DAHPS, DQD/SDH, PAL, 4CL, CHS, CHI, F3H, F3'H, FLS, and UGT78D2, and their corresponding metabolites were elaborately characterized. Our research reveals the molecular and chemical mechanisms of the fruit development of R. chingii. The results provide a solid foundation for the genetic analysis, functional genes isolation, fruit quality improvement and modifiable breeding of R. chingii.
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http://dx.doi.org/10.1007/s00299-021-02758-6DOI Listing
July 2021
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