Publications by authors named "Jinghua Yang"

145 Publications

Aluminum impairs cognitive function by activating DDX3X-NLRP3-mediated pyroptosis signaling pathway.

Food Chem Toxicol 2021 Oct 3;157:112591. Epub 2021 Oct 3.

Department of Toxicology, School of Public Health, China Medical University, Shenyang, 110122, PR China. Electronic address:

Introduction: Aluminum is a kind of chemical contaminants in food which can induce neurotoxicity. Aluminum exposure is closely related to neurodegenerative diseases (ND), in which neuroinflammation might involve. However, the molecular mechanism of aluminum-induced neuroinflammation through pyroptosis is not fully clarified yet.

Material And Methods: The mice model of subacute exposure to aluminum chloride (AlCl) was established. BV2 microglia cells was treated with AlCl in vitro. Resveratrol (Rsv) was adopted as intervention agent.

Results: Our results showed that aluminum induced cognitive impairment, destroying blood brain barrier (BBB), and causing nerve injury in mice. Meanwhile, aluminum could stimulate nucleotide oligomerization domain-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome assembly and activate caspase-1 (CASP1), inducing gasdermin D (GSDMD)-mediated pyroptosis signaling, releasing cytokines IL-1β and IL-18, further promoting the activation of glial cells to magnify neuroinflammatory response. Moreover, DEAD-box helicase 3 X-linked (DDX3X) and stress granule RasGAP SH3-domain-binding protein 1 (G3BP1) both participated in neuroinflammation induced by aluminum. When co-treated with Rsv, these injuries were alleviated to some extent.

Conclusion: Aluminum exposure could induce nerve cell pyroptosis and neuroinflammation by DDX3X-NLRP3 inflammasome signaling pathway, which could be rescued via Rsv activating sirtuin 1 (SIRT1).
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http://dx.doi.org/10.1016/j.fct.2021.112591DOI Listing
October 2021

Postural Stability Change Under Sleep Deprivation and Mental Fatigue Status.

Aerosp Med Hum Perform 2021 Aug;92(8):627-632

From the Department of Aerospace Medical Equipment, School of Aerospace Medicine, Air Force Medical University, and the Fundamentals Department, Air Force Engineering University, Xian, Peoples Republic of China.

Based on posturography parameters during sleep deprivation (SD), a mental fatigue index (MFI) was constructed for healthy male cadets. There were 37 young male subjects who volunteered for two successive days of SD. Their posturography balance, profile of mood status (POMS), and heart rate variability (HRV) were measured at four different times (10:00 and 22:00 of day 1, 10:00 and 22:00 of day 2). According to the methods used in our previous research, similar MFIs based on posturography parameters were computed. Then, correlations of MFIs with POMS scores and HRV values were evaluated by linear and nonlinear methods including quadratic, S-curve, growth, and exponential analyses. MFI continued to increase during SD and MFI as the independent variable had quadratic relationships with fluster (R² 0.057), depression (R² 0.067), and anger (R² 0.05) scores of POMS. A linear correlation was found between MFI and the depression score (R² 0.045) and MFI correlated linearly (R² 0.029) and nonlinearly (R² 0.03) with heart rate. Similarly, MFI reflected changes in the time and frequency domain parameters of HRV, with linear (R²range: 0.0290.082) or nonlinear (R²range: 0.0300.082) relationships. The increase of MFI was linked with amplification of personal negative moods and an imbalance of autonomic nervous system activity. The findings suggest that MFI might be a potential indicator of mental fatigue and provide a method to prevent driving fatigue and human errors.
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http://dx.doi.org/10.3357/AMHP.5755.2021DOI Listing
August 2021

Genomic signatures of vegetable and oilseed allopolyploid Brassica juncea and genetic loci controlling the accumulation of glucosinolates.

Plant Biotechnol J 2021 Aug 27. Epub 2021 Aug 27.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou, China.

Allopolyploid Brassica juncea crops in Brassicaceae are becoming increasingly revitalized as vegetables and oilseeds owing to wide adaptability and significant economic values. However, the genomic differentiation of diversified vegetables and oilseed B. juncea and the genetic basis underlying glucosinolates accumulation have yet to be elucidated. To address this knowledge gap, we report the sequencing of pairwise genomes of vegetable and oilseed B. juncea at chromosome scale. Comparative genomics analysis unveils panoramic structural variation footprints, particularly the genetic loci of HSP20 and TGA1 associated with abiotic and biotic stresses responses between oilseed and vegetable subgroups. We anchored two major loci of MYB28 (HAG1) orthologues caused by copy number variations on A02 and A09 chromosomes using scored genomic SNPs-based GWAS that are responsible for seed oil quality-determining glucosinolates biosynthesis. These findings will provide valuable repertories of polyploidy genomic information enabling polyploidy genome evolution studies and precise genomic selections for crucial traits like functional components of glucosinolates in B. juncea crops and beyond.
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http://dx.doi.org/10.1111/pbi.13687DOI Listing
August 2021

Permissive action of HO mediated ClUGT75 expression for auxin glycosylation and Al- tolerance in watermelon.

Plant Physiol Biochem 2021 Oct 24;167:77-90. Epub 2021 Jul 24.

Laboratory of Germplasm Innovation and Molecular Breeding, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 310058, PR China; Hainan Institute of Zhejiang University, Yazhou District, Sanya, 572025, PR China; Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou, 310058, PR China.

Although Al-toxicity is one of the limiting factors for crop production in acidic soils, little is known about the Al-tolerance mechanism in watermelon, a fairly acid-tolerant crop. This work aimed to identify the interaction between the HO scavenging pathway and auxin glycosylation relevant to watermelon Al-tolerance. By analyzing expressions of hormone-related ClUGTs and antioxidant enzyme genes in Al-tolerant (ZJ) and Al-sensitive (NBT) cultivars, we identified ClUGT75s (B1, B2, and D1) and ClSOD1-2-ClCAT as crucial components associated with Al-tolerance. Al-stress significantly increased HO content by 92.7% in NBT and 42.3% in ZJ, accompanied by less Al-, auxin (IAA and IBA), and MDA contents in ZJ than NBT. These findings coincided with significant ClSOD1-2 expression and stable dismutation activity in NBT than ZJ. Hence, higher HO content in the root apex of NBT than ZJ correlated with a significant increase in auxin content and ClSOD1-2 up-regulation. Moreover, Al-activated ClUGT75D1 and ClUGT75B2 in ZJ coincided with no considerable change in IBA content, suggesting that glycosylation-mediated changes in IBA content might be relevant to Al-tolerance in watermelon. Furthermore, exogenous HO and IBA indicated ClUGT75D1 modulating IBA is likely dependent on HO background. We hypothesize that a higher HO level in NBT represses ClUGT75, resulting in increased auxin than those in ZJ roots. Thus, excess in both HO and auxin aggravated the inhibition of root elongation under Al-stress. Our findings provide insights on the permissive action of HO in the mediation of auxin glycosylation by ClUGT75 in root apex for Al-tolerance in watermelon.
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http://dx.doi.org/10.1016/j.plaphy.2021.07.022DOI Listing
October 2021

Benzo[a]pyrene diol epoxide-induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1-derived circular RNA in pulmonary squamous cell carcinoma.

Mol Carcinog 2021 10 28;60(10):684-701. Epub 2021 Jul 28.

Department of Toxicology, School of Public Health, China Medical University, Shenyang, Liaoning, China.

ERCC1 is a gene for repairing DNA damage whose function is related to carcinogenic-induced tumorigenesis and the effectiveness of platinum therapies. Circular RNAs (circRNAs) are products of posttranscriptional regulation with pleiotropic effects on the pathogenesis of lung cancer. We aim to identify that specific circRNAs derived from ERCC1 can regulate key biological processes involved in the development of lung cancer. We performed bioinformatics analysis, in vitro experiments, and analyzed clinical samples, to determine the biological features of a certain ERCC1-derived circRNA termed as hsa_circ_0051488 in benzo[a]pyrene diol epoxide-induced malignant transformed cell and lung cancer cell. The well-established model of transformed cells provided an ideal platform for analyzing the molecular characteristics of this circRNA in the malignant transformation of lung epithelial cell, which supports that hsa_circ_0051488 functions in the onset and growth of lung squamous cell carcinoma (LUSC). Further analysis indicates that the absence of hsa_circ_0051488 promoted the proliferation of cells with the malignant phenotype. Extensive experiments confirm that hsa_circ_0051488 is present in the cytoplasm and functioned as a competing endogenous RNA. In particular, hsa_circ_0051488 binds to mir-6717-5p, thereby modulating the expression of SATB2 gene, a lung cancer suppressor. Furthermore, our in silico experiments indicate that SATB2 can inhibit multiple tumor pathways and its expression positively correlated with the tumor suppressor gene CRMP1. These findings suggest a possible regulatory mechanism of hsa_circ_0051488 in LUSC, and that the newly discovered hsa_circ_0051488/miR-6717-5p/SATB2 axis may be a potential route for therapeutic intervention of LUSC.
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http://dx.doi.org/10.1002/mc.23335DOI Listing
October 2021

Synthesis of POMOFs with 8-fold helix and its composite with carboxyl functionalized SWCNTs for the voltammetric determination of dopamine.

Anal Bioanal Chem 2021 Sep 15;413(21):5309-5320. Epub 2021 Jul 15.

The Talent Culturing Plan for Leading Disciplines of Shandong Province, Department of Chemistry and Chemical Engineering, Jining University, Qufu, Shandong, 273155, People's Republic of China.

Although many satisfactory studies have been developed for biomolecule detection, the complexity of biofluids still poses a major challenge to improve the performance of nanomaterials as electrochemical sensors. Herein, unprecedented polyoxometalate-based metal-organic frameworks (POMOFs) with 8-fold meso-helical feature, [Ag(trz)][PMoO] (PAZ), were synthesized and explored as electrochemical sensors to detect dopamine (DA). To improve the conductivity of PAZ and the binding ability with single-walled carbon nanotubes (SWCNTs), the nanocomposite of carboxyl functionalized SWCNTs (SWCNTs-COOH) with nano-PAZ (NPAZ), [email protected], was fabricated, and transmission electron microscopy (TEM) shows that NPAZ can interact stably and uniformly with SWCNTs-COOH, owing to more defect sites on the surface of SWCNTs-COOH. The electrochemical result of [email protected]/GCE towards detecting DA shows that the linear range was from 0.05 to 100 μM with a detection limit (LOD) of 8.6 nM (S/N = 3). A new electrochemical biosensing platform by combining 8-fold helical POMOFs with SWCNTs-COOH was developed for enhancing detection of dopamine for the first time, exhibiting the lowest detection limit to date.
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http://dx.doi.org/10.1007/s00216-021-03504-3DOI Listing
September 2021

Genome structural evolution in Brassica crops.

Nat Plants 2021 06 27;7(6):757-765. Epub 2021 May 27.

Department of Biology, University of York, York, UK.

The cultivated Brassica species include numerous vegetable and oil crops of global importance. Three genomes (designated A, B and C) share mesohexapolyploid ancestry and occur both singly and in each pairwise combination to define the Brassica species. With organizational errors (such as misplaced genome segments) corrected, we showed that the fundamental structure of each of the genomes is the same, irrespective of the species in which it occurs. This enabled us to clarify genome evolutionary pathways, including updating the Ancestral Crucifer Karyotype (ACK) block organization and providing support for the Brassica mesohexaploidy having occurred via a two-step process. We then constructed genus-wide pan-genomes, drawing from genes present in any species in which the respective genome occurs, which enabled us to provide a global gene nomenclature system for the cultivated Brassica species and develop a methodology to cost-effectively elucidate the genomic impacts of alien introgressions. Our advances not only underpin knowledge-based approaches to the more efficient breeding of Brassica crops but also provide an exemplar for the study of other polyploids.
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http://dx.doi.org/10.1038/s41477-021-00928-8DOI Listing
June 2021

Cathodal Transcranial Direct Current Stimulation Over the Right Temporoparietal Junction Suppresses Its Functional Connectivity and Reduces Contralateral Spatial and Temporal Perception.

Front Neurosci 2021 17;15:629331. Epub 2021 Feb 17.

Air Force Medical Center, Air Force Medical University, Beijing, China.

The temporoparietal junction plays key roles in vestibular function, motor-sensory ability, and attitude stability. Conventional approaches to studying the temporoparietal junction have drawbacks, and previous studies have focused on self-motion rather than on vestibular spatial perception. Using transcranial direct current stimulation, we explored the temporoparietal junction's effects on vestibular-guided orientation for self-motion and vestibular spatial perception. Twenty participants underwent position, motion, and time tasks, as well as functional magnetic resonance imaging scans. In the position task, cathodal transcranial direct current stimulation yielded a significantly lower response in the -6, -7, -8, -9, -10, -11, and -12 stimulus conditions for leftward rotations ( < 0.05). In the time task, the temporal bias for real transcranial direct current stimulation significantly differed from that for sham stimulation ( < 0.01). Functional magnetic resonance imaging showed that cathodal transcranial direct current stimulation suppressed functional connectivity between the temporoparietal junction, right insular cortex, and right supplementary motor area. Moreover, the change in connectivity between the right temporoparietal junction seed and the right insular cortex was positively correlated with temporal bias under stimulation. The above mentioned results show that cathodal transcranial direct current stimulation induces immediate and extended vestibular effects, which could suppress the functional connectivity of the temporoparietal junction and in turn reduce contralateral spatial and temporal perception. The consistent variation in temporal and spatial bias suggested that the temporoparietal junction may be the cortical temporal integrator for the internal model. Moreover, transcranial direct current stimulation could modulate the integration process and may thus have potential clinical applications in vestibular disorders caused by temporoparietal junction dysfunction.
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http://dx.doi.org/10.3389/fnins.2021.629331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925883PMC
February 2021

Brassica carinata genome characterization clarifies U's triangle model of evolution and polyploidy in Brassica.

Plant Physiol 2021 May;186(1):388-406

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou 310058, China.

Ethiopian mustard (Brassica carinata) in the Brassicaceae family possesses many excellent agronomic traits. Here, the high-quality genome sequence of B. carinata is reported. Characterization revealed a genome anchored to 17 chromosomes with a total length of 1.087 Gb and an N50 scaffold length of 60 Mb. Repetitive sequences account for approximately 634 Mb or 58.34% of the B. carinata genome. Notably, 51.91% of 97,149 genes are confined to the terminal 20% of chromosomes as a result of the expansion of repeats in pericentromeric regions. Brassica carinata shares one whole-genome triplication event with the five other species in U's triangle, a classic model of evolution and polyploidy in Brassica. Brassica carinata was deduced to have formed ∼0.047 Mya, which is slightly earlier than B. napus but later than B. juncea. Our analysis indicated that the relationship between the two subgenomes (BcaB and BcaC) is greater than that between other two tetraploid subgenomes (BjuB and BnaC) and their respective diploid parents. RNA-seq datasets and comparative genomic analysis were used to identify several key genes in pathways regulating disease resistance and glucosinolate metabolism. Further analyses revealed that genome triplication and tandem duplication played important roles in the expansion of those genes in Brassica species. With the genome sequencing of B. carinata completed, the genomes of all six Brassica species in U's triangle are now resolved. The data obtained from genome sequencing, transcriptome analysis, and comparative genomic efforts in this study provide valuable insights into the genome evolution of the six Brassica species in U's triangle.
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http://dx.doi.org/10.1093/plphys/kiab048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154070PMC
May 2021

Identification and characterization of a natural SNP variant in ALTERNATIVE OXIDASE gene associated with cold stress tolerance in watermelon.

Plant Sci 2021 Mar 2;304:110735. Epub 2020 Nov 2.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou 310058, PR China; Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou 310058, PR China.

Alternative oxidase (AOX) is a mitochondrial enzyme encoded by a small nuclear gene family, which contains the two subfamilies, AOX1 and AOX2. In the present study on watermelon (Citrullus lanatus), only one ClAOX gene, belonging to AOX2 subfamily but having a similar gene structure to AtAOX1a, was found in the watermelon genome. The expression analysis suggested that ClAOX had the constitutive expression feature of AOX2 subfamily, but was cold inducible, which is normally considered an AOX1 subfamily feature. Moreover, one single nucleotide polymorphism (SNP) in ClAOX sequence, which led to the change from Lys (N) to Asn (K) in the 96 amino acids, was found among watermelon subspecies. Ectopic expression of two ClAOX alleles in the Arabidopsis aox1a knock-out mutant indicated that ClAOX-expressing plants had stronger cold tolerance than aox1a mutant and ClAOX-expressing plants. Our findings suggested watermelon genome contained a single ClAOX that possessed the expression features of both AOX1 and AOX2 subfamilies. A naturally existing SNP in ClAOX differentiated the cold tolerance of transgenic Arabidopsis plants, impling a possibility this gene might be a functional marker for stress-tolerance breeding.
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http://dx.doi.org/10.1016/j.plantsci.2020.110735DOI Listing
March 2021

Brassicaceae transcriptomes reveal convergent evolution of super-accumulation of sinigrin.

Commun Biol 2020 12 16;3(1):779. Epub 2020 Dec 16.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, 310058, Hangzhou, China.

Wasabi, horseradish and mustard are popular pungent crops in which the characteristic bioactive hydrolysis of specialized glucosinolates (GSLs) occurs. Although the metabolic pathways of GSLs are well elucidated, how plants have evolved convergent mechanisms to accumulate identical GSL components remains largely unknown. In this study, we discovered that sinigrin is predominantly synthesized in wasabi, horseradish and mustard in Brassicaceae. We de novo assembled the transcriptomes of the three species, revealing the expression patterns of gene clusters associated with chain elongation, side chain modification and transport. Our analysis further revealed that several gene clusters were convergently selected during evolution, exhibiting convergent shifts in amino acid preferences in mustard, wasabi and horseradish. Collectively, our findings provide insights into how unrelated crop species evolve the capacity for sinigrin super-accumulation and thus promise a potent strategy for engineering metabolic pathways at multiple checkpoints to fortify bioactive compounds for condiment or pharmaceutical purposes.
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http://dx.doi.org/10.1038/s42003-020-01523-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745032PMC
December 2020

Lanthanum chloride causes blood-brain barrier disruption through intracellular calcium-mediated RhoA/Rho kinase signaling and myosin light chain kinase.

Metallomics 2020 12;12(12):2075-2083

Department of Occupational and Environmental Health, School of Public Health, Jinzhou Medical University, #40 Section Three Songpo Road, Jinzhou 121001, P. R. China.

Rare earth elements (REEs) have caused bioaccumulation and adverse health effects attributed to extensive application. The penetrability of REEs across the blood-brain barrier (BBB) contributes to their neurotoxicity process, but potential mechanisms affecting BBB integrity are still obscure. The present study was designed to investigate the effects of lanthanum on BBB adheren junctions and the actin cytoskeleton in vitro using bEnd.3 cells. After lanthanum chloride (LaCl3, 0.125, 0.25 and 0.5 mM) treatment, cytotoxicity against bEnd.3 cells was observed accompanied by increased intracellular Ca2+. Higher paracellular permeability presented as decreased TEER (transendothelial electrical resistance) and increased HRP (horse radish peroxidase) permeation, and simultaneously reduced VE-cadherin expression and F-actin stress fiber formation caused by LaCl3 were reversed by inhibition of ROCK (Rho-kinase) and MLCK (myosin light chain kinase) using inhibitor Y27632 (10 μM) and ML-7 (10 μM). Moreover, chelating overloaded intracellular Ca2+ by BAPTA-AM (25 μM) remarkably abrogated RhoA/ROCK and MLCK activation and downstream phosphorylation of MYPT1 (myosin phosphatase target subunit 1) and MLC2 (myosin light chain 2), therefore alleviating LaCl3-induced BBB disruption and dysfunction. In conclusion, this study indicated that lanthanum caused endothelial barrier hyperpermeability accompanied by loss of VE-cadherin and rearrangement of the actin cytoskeleton though intracellular Ca2+-mediated RhoA/ROCK and MLCK pathways.
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http://dx.doi.org/10.1039/d0mt00187bDOI Listing
December 2020

Identification and characterization of Arabidopsis thaliana mitochondrial FF-ATPase inhibitor factor 1.

J Plant Physiol 2020 Nov 22;254:153264. Epub 2020 Sep 22.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou, 310058, China.

Mitochondrial FF-ATP synthase (FF-ATPase) inhibitor factor 1 (IF1) has been extensively characterized as an endogenous inhibitor that prevents the hydrolysis of adenosine-5'-triphosphate (ATP) by mitochondrial ATPases in mammals and yeasts; however, IF1's functions in plants remain unclear. Here, a comprehensive bioinformatic analysis was performed to identify plant mitochondrial FF-ATPase IF1 orthologs. Plant IF1s contain a conserved FF-ATPase inhibitory domain, but lack the antiparallel α-helical coiled-coil structure compared with mammalian IF1s. A subcellular localization analysis in Arabidopsis thaliana revealed that AtIF1-green fluorescent protein was present only in mitochondria. Additionally, AtIF1 was widely expressed in diverse organs and intense β-glucuronidase staining was observed in reproductive tissues and germinating seeds. Compared with the wild-type and p35S:AtIF1-if1 etiolated seedlings, the ATP/ADP ratio was significantly lower in the AtIF1 T-DNA knockout seedlings (if1 mutant) growing under dark conditions, suggesting that AtIF1 can influence the energy state of cells. A significant reduction in seed yield and strong growth retardation under dark conditions were observed in the if1 mutant line. Furthermore, if1 plants exhibited a substantially decreased sensitivity to abscisic acid. Thus, the A. thaliana mitochondrial IF1, which is a conserved FF-ATPase inhibitor, is crucial for plant growth and responses to abscisic acid.
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http://dx.doi.org/10.1016/j.jplph.2020.153264DOI Listing
November 2020

MutS HOMOLOG1 mediates fertility reversion from cytoplasmic male sterile Brassica juncea in response to environment.

Plant Cell Environ 2021 01 31;44(1):234-246. Epub 2020 Oct 31.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou, China.

Spontaneous fertility reversion has been documented in cytoplasmic male sterile (CMS) plants of several species, influenced in frequency by nuclear genetic background. In this study, we found that MutS HOMOLOG1 (MSH1) mediates fertility reversion via substoichiometric shifting (SSS) of the CMS-associated mitochondrial Open Reading Frame 220 (ORF220), a process that may be regulated by pollination signalling in Brassica juncea. We show that plants adjust their growth and development in response to unsuccessful pollination. Measurable decrease in MSH1 transcript levels and evidence of ORF220 SSS under non-pollination conditions suggest that this nuclear-mitochondrial interplay influences fertility reversion in CMS plants in response to physiological signals. Suppression of MSH1 expression induced higher frequency SSS in CMS plants than occurs normally. Transcriptional analysis of floral buds under pollination and non-pollination conditions, and the response of MSH1 expression to different sugars, supports the hypothesis that carbon flux is involved in the pollination signalling of fertility reversion in CMS plants. Our findings suggest that facultative gynodioecy as a reproductive strategy may incorporate environmentally responsive genes like MSH1 as an "on-off" switch for sterility-fertility transition under ecological conditions of reproductive isolation.
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http://dx.doi.org/10.1111/pce.13895DOI Listing
January 2021

Subcellular distribution of aluminum associated with differential cell ultra-structure, mineral uptake, and antioxidant enzymes in root of two different Al-resistance watermelon cultivars.

Plant Physiol Biochem 2020 Oct 28;155:613-625. Epub 2020 Jul 28.

Laboratory of Germplasm Innovation and Molecular Breeding, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 310058, PR China; Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agriculture, Hangzhou, 310058, PR China.

Crop plants, such as watermelon, suffer from severe Aluminum (Al)-toxicity in acidic soils with their primary root elongation being first arrested. However, the significance of apoplastic or symplastic Al-toxicity in watermelon root is scarcely reported. In this work, we identified a medium fruit type (ZJ) and a small fruit type (NBT) as Al-tolerant and sensitive based on their differential primary root elongation rate respectively, and used them to show the effects of symplastic besides apoplastic Al distribution in the watermelon's root. Although the Al content was higher in the root of NBT than ZJ, Al allocated in their apoplast, vacuole and plastid fractions were not significantly different between the two cultivars. Thus, only a few proportion of Al differentially distributed in the nucleus and mitochondria corresponded to interesting differential morphological and physiological disorders recorded in the root under Al-stress. The symplastic amount of Al substantially induced the energy efficient catalase pathway in ZJ, and the energy consuming ascorbate peroxidase pathway in NBT. These findings coincided with obvious starch granule visibility in the root ultra-structure of ZJ than NBT, suggesting a differential energy was used in supporting the root elongation and nutrient uptake for Al-tolerance in the two cultivars. This work provides clues that could be further investigated in the identification of genetic components and molecular mechanisms associated with Al-tolerance in watermelon.
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http://dx.doi.org/10.1016/j.plaphy.2020.06.045DOI Listing
October 2020

The Chromosome-Scale Genome of Melon Dissects Genetic Architecture of Important Agronomic Traits.

iScience 2020 Aug 29;23(8):101422. Epub 2020 Jul 29.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Horticultural Plant Growth and Development, Ministry of Agriculture and Rural Affairs, Hangzhou 310058, China. Electronic address:

Comparative and evolutionary genomics analyses are the powerful tools to provide mechanistic insights into important agronomic traits. Here, we completed a chromosome-scale assembly of the "neglected" but vital melon subspecies Cucumis melo ssp. agrestis using single-molecule real-time sequencing, Hi-C, and an ultra-dense genetic map. Comparative genomics analyses identified two targeted genes, UDP-sugar pyrophosphorylase and α-galactosidase, that were selected during evolution for specific phloem transport of oligosaccharides in Cucurbitaceae. Association analysis of transcriptome and the DNA methylation patterns revealed the epigenetic regulation of sucrose accumulation in developing fruits. We constructed the melon recombinant inbred lines to uncover Alkaline/Neutral Invertase (CINV), Sucrose-Phosphatase 2 (SPP2), α-galactosidase, and β-galactosidase loci related to sucrose accumulation and an LRR receptor-like serine/threonine-protein kinase associated with gummy stem blight resistance. This study provides essential genomic resources enabling functional genomics studies and the genomics-informed breeding pipelines for improving the fruit quality and disease resistance traits.
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http://dx.doi.org/10.1016/j.isci.2020.101422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452659PMC
August 2020

The casein kinase 2 β subunit CK2B1 is required for swollen stem formation via cell cycle control in vegetable Brassica juncea.

Plant J 2020 11 3;104(3):706-717. Epub 2020 Sep 3.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou, 310058, China.

The swollen stem is a determinant of yield for the stem-type vegetable Brassica juncea that is representative of vegetative organ formation. However, the genetic mechanism underlying swollen stem formation and its regulation remains unknown. In this study, we identified a casein kinase 2 β subunit 1 (CK2B1) and revealed its role in swollen stem formation. Genotyping analysis revealed that a homozygous variation in the CK2B1 promoter is responsible for swollen stem formation, and the promoter activity of CK2B1 was significantly associated with the variations between swollen stem and non-swollen stem types. CK2B1 was exclusively located in the nucleus and expressed in the stem nodes of the plant. Swollen stem formation was blocked when CK2B1 expression was silenced, and induced in a backcross population carrying a swollen stem genotype, which indicates that CK2B1 is required for swollen stem formation. Cell numbers were increased during swollen stem formation and decreased in CK2B1-silenced expression plant, indicating that CK2B1 regulates swollen stem formation via cell division. CK2B1 directly interacted with E2Fa, a regulator of G1/S transition in the cell cycle, in which CK2 phosphorylates E2Fa. Our results revealed that CK2B1 affects swollen stem formation via the control of the cell cycle. These findings help to elucidate the signals that control swollen stem formation and provide a promising molecular target to enhance the yield of vegetative organ formation.
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http://dx.doi.org/10.1111/tpj.14958DOI Listing
November 2020

Protein O-mannosylation affects protein secretion, cell wall integrity and morphogenesis in Trichoderma reesei.

Fungal Genet Biol 2020 11 3;144:103440. Epub 2020 Aug 3.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing, China; National Engineering Research Center for Non-food Bio-refinery, Guangxi Academy of Sciences, Nanning 530007, Guangxi, China. Electronic address:

Protein O-mannosyltransferases (PMTs) initiate O-mannosylation of proteins in the ER. Trichoderma reesei strains displayed a single representative of each PMT subfamily, Trpmt1, Trpmt2 and Trpmt4. In this work, two knockout strains ΔTrpmt1and ΔTrpmt4were obtained. Both mutants showed retarded growth, defective cell walls, reduced conidiation and decreased protein secretion. Additionally, the ΔTrpmt1strain displayed a thermosensitive growth phenotype, while the ΔTrpmt4 strain showed abnormal polarity. Meanwhile, OETrpmt2 strain, in which the Trpmt2 was over-expressed, exhibited increased conidiation, enhanced protein secretion and abnormal polarity. Using a lectin enrichment method and MS/MS analysis, 173 O-glycoproteins, 295 O-glycopeptides and 649 O-mannosylation sites were identified as the targets of PMTs in T. reesei. These identified O-mannoproteins are involved in various physiological processes such as protein folding, sorting, transport, quality control and secretion, as well as cell wall integrity and polarity. By comparing proteins identified in the mutants and its parent strain, the potential specific protein substrates of PMTs were identified. Based on our results, TrPMT1 is specifically involved inO-mannosylation of intracellular soluble proteins and secreted proteins, specially glycosidases. TrPMT2 is involved inO-mannosylation of secreted proteins and GPI-anchor proteins, and TrPMT4 mainly modifies multiple transmembrane proteins. The TrPMT1-TrPMT4 complex is responsible for O-mannosylation of proteins involved in cell wall integrity. Overexpression of TrPMT2 enhances protein secretion, which might be a new strategy to improve expression efficiency in T. reesei.
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http://dx.doi.org/10.1016/j.fgb.2020.103440DOI Listing
November 2020

Comprehensive profiling of Stephania tetrandra (Fangji) by stepwise DFI and NL-dependent structure annotation algorithm-based UHPLC-Q-TOF-MS and direct authentication by LMJ-HRMS.

J Pharm Biomed Anal 2020 Jun 3;185:113225. Epub 2020 Mar 3.

Research Center for Clinical Systems Biology, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. Electronic address:

Stephania tetrandra S. Moore, a widely used traditional antirheumatic herbal medicine (HM), is a rich source of isoquinoline alkaloids. With the exception of the two recognized isoquinolines, viz. tetrandrine and fangchinoline, the other isoquinoline alkaloids present in S. tetrandra have not been clearly clarified. In addition, due to their similar names and morphological similarities, S. tetrandra is often mistakenly substituted and adulterated with the nephrotoxic Aristolochia fangchi. In this study, ultra-high-performance liquid chromatography-triple time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was initially employed to comprehensively profile the isoquinolines from S. tetrandra. To overcome the complexities arising due to the similar mass behaviors of the isoquinolines, a stepwise diagnostic fragment ion (DFI) and neutral loss (NL)-dependent structure annotation algorithm was proposed, and this accelerated the identification of 393 isoquinolines distributed over twenty classes. Consequently, liquid microjunction surface sampling-high-resolution mass spectrometry (LMJ-HRMS) was deployed in an attempt to directly authenticate S. tetrandra by the chemical profiling of its crude slice. By matching the 393 isoquinolines, the 87 peaks detected by LMJ-HRMS were assigned to 270 isoquinolines, including the recognized tetrandrine and fangchinoline. The absence of aristolochic acid-related mass signals confirmed the authentication of S. tetrandra. In summary, LMJ-HRMS can be considered a direct, nondestructive, high-throughput, and environment-friendly analytical method for the authentication of HMs. Moreover, the stepwise DFI- and NL-dependent structure annotation algorithm-based UHPLC-Q-TOF-MS method allowed high-coverage detection and high-quality data processing of the inherent structural similarity and complexity of isoquinolines or other phytochemical compounds.
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http://dx.doi.org/10.1016/j.jpba.2020.113225DOI Listing
June 2020

Lanthanum chloride impairs spatial learning and memory by inducing [Ca] overload, mitochondrial fission-fusion disorder and excessive mitophagy in hippocampal nerve cells of rats.

Metallomics 2020 04 12;12(4):592-606. Epub 2020 Mar 12.

Department of Toxicology, School of Public Health, China Medical University, No. 77 Puhe road, Shenyang North New Area, Shenyang 110112, Liaoning Province, People's Republic of China.

Lanthanum (La) is a kind of rare earth element (REE) widely found in nature. La has neurotoxicity and can impair learning and memory, but the underlying mechanism is still not completely clear. The mitochondrial calcium uniporter (MCU) complex can cause the uptake of cytoplasmic calcium ([Ca]) into mitochondria and thereby resist [Ca] overload. However, the abnormal increase of calcium in the mitochondrial matrix ([Ca]) can also disturb the mitochondrial fission-fusion balance, and then induce excessive mitophagy, and disrupt mitochondrial quality control (MQC). It is unclear whether La can interfere with the function of nerve cells through the above-mentioned mechanism and thus impair learning and memory. In this study, four groups of Wistar rats were treated with 0%, 0.25%, 0.5% and 1.0% (w/v) lanthanum chloride (LaCl) from the embryonic phase to 1 month after weaning. The results showed that La could impair the spatial learning and memory of rats, promote the uptake of [Ca] by MCU, induce the abnormal increase of [Ca], up-regulate p-Drp1 Ser616 expression and inhibit Mfn1/2 expression, enhance mitochondrial fission and lead to mitochondrial fission-fusion disturbance in hippocampal nerve cells. Meanwhile, La could also activate the PINK1-Parkin signaling pathway, up-regulate LC3B-II expression and decrease p62 expression, and thereby induce excessive mitophagy. These results suggested that learning and memory impairment caused by La may be related to MQC disturbance. The present data provide some novel clues for elucidating the neurotoxic effect mechanism of La.
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http://dx.doi.org/10.1039/c9mt00291jDOI Listing
April 2020

Identification of eukaryotic translation initiation factors and the temperature-dependent nature of epidemics in allopolyploid .

3 Biotech 2020 Feb 28;10(2):75. Epub 2020 Jan 28.

1Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou, 310058 China.

Eukaryotic translation initiation factors () are essential protein complexes involved in the translation of mRNA into proteins. These initiation factors are generally used as targets in the control of plant RNA virus infections. In the present study, we identified a total 190 s, clustered phylogenetically into 40 distinct subfamilies in the allopolyploid . Extensive evolutionary duplications of the s in suggest their increased genetic diversity and wide adaptability. The induction of expressions in some of the after inoculation against (TuMV) provided candidate targets to be used in the control of viral infections. In addition, the expression profiles of under different temperatures suggested that the TuMV epidemic was temperature dependent. The expressions suggested that the systemic viral infections were more acute in plants grown between 20 °C and 28 °C. In addition, our results revealed that new subgroups of , , , , , and could be represented as targets for antiviral strategies in . In summary, our findings would be helpful in studying the complex mechanisms of -mediated, temperature-dependent RNA virus control in .
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http://dx.doi.org/10.1007/s13205-020-2058-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987279PMC
February 2020

Lanthanum Chloride Impairs Learning and Memory and Induces Dendritic Spine Abnormality by Down-Regulating Rac1/PAK Signaling Pathway in Hippocampus of Offspring Rats.

Cell Mol Neurobiol 2020 Apr 27;40(3):459-475. Epub 2019 Nov 27.

Department of Toxicology, School of Public Health, China Medical University, NO.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, People's Republic of China.

Lanthanum (La) is a natural rare earth element. It has neurotoxic effects which can impair learning and memory in humans. However, its mechanism of neurotoxicity is unclear. Learning and memory are coordinated by dendritic spines which form tiny protruding structures on the dendritic branches of neurons. This study investigated the effect of LaCl exposure to pregnant and lactating rats on the offspring rats' learning and memory ability. In this study, rats were divided into 4 groups and given distilled water solution containing 0%, 0.125%, 0.25%, 0.5% LaCl, respectively, and this was done from conception to the end of the location. The effects of LaCl on spatial learning and memory ability in offspring rats and in the development of dendritic spines in CA1 pyramidal cells were investigated. The results showed that LaCl impaired spatial learning and memory ability in offspring rats, and decreased dendritic spine density during development. In addition, LaCl can affect the expression of CaMKII, miRNA132, p250GAP, Tiam1, PARD3, and down-regulated the activation of Rac1 which led to a decrease in the expression of Rac1/PAK signaling pathway and downstream regulatory proteins Cortactin and actin-related protein 2/3 complex (Arp2/3 complex). This study indicated that the learning and memory impairment and the decrease of dendritic spine density in the offspring of LaCl exposure may be related to the down-regulation of the Rac1/PAK signaling pathway regulated by Tiam1 and p250GAP.
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http://dx.doi.org/10.1007/s10571-019-00748-7DOI Listing
April 2020

Efficacy of zoledronic acid for prevention of bone loss in early-stage breast cancer patients receiving adjuvant therapy: A meta-analysis of 13 randomized controlled trials.

Curr Probl Cancer 2020 04 1;44(2):100507. Epub 2019 Nov 1.

Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China. Electronic address:

Early-stage breast cancer (BC) patients receiving adjuvant therapy suffer from bone loss and increased fracture risk. Zoledronic acid (ZA) has been confirmed to inhibit bone metastasis and improve survival outcomes in early BC postmenopausal patients receiving adjuvant therapy. However, the efficacy of ZA for prevention of adjuvant therapy-induced bone loss from 2 different early BC groups, namely premenopausal and postmenopausal patients, still remain unclear. To obtain detailed characteristics, we performed this meta-analysis. PubMed, EMBASE, and Cochrane were searched. In premenopausal BC patients and postmenopausal BC patients, to assess bone loss, we calculated the weighted mean differences with 95% confidence intervals (CI) to evaluate lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and femoral neck (FN) BMD in ZA and non-ZA group with follow-up of 12 months. Thirteen randomized controlled trials (RCTs) encompassing 7375 patients were included. In a mixed population of early BC patients receiving adjuvant therapy, ZA significantly increased LS BMD (P < 0.00001), TH BMD (P < 0.00001), and FN BMD (P = 0.01) compared with non-ZA group. In premenopausal patient subgroup, LS BMD was greatly higher in patients with ZA compared to controls (0.06 g/cm; 95% CI: 0.05-0.08), whereas there were no differences in TH BMD and FN BMD between patients with ZA and controls. In postmenopausal patient subgroup, both LS BMD (0.06 g/cm; 95% CI: 0.05-0.07) and TH BMD (0.04 g/cm; 95% CI: 0.03-0.04) were significantly higher in patients with ZA compared to controls, but there was no difference in FN BMD between patients with ZA and controls. To sum up, ZA prevents bone loss in early-stage BC patients receiving adjuvant therapy at different skeletal sites. In premenopausal patients, effectiveness of ZA in prevention of bone loss is confirmed at LS site, but not at TH and FN site. In postmenopausal patients, ZA has a satisfying efficacy for prevention of bone loss at LS and TH site, but not at FN site.
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http://dx.doi.org/10.1016/j.currproblcancer.2019.100507DOI Listing
April 2020

Activation of Nrf2 by lead sulfide nanoparticles induces impairment of learning and memory.

Metallomics 2020 01;12(1):34-41

Department of Toxicology, School of Public Health, China Medical University, Shenyang 110001, China.

Lead sulfide nanoparticles (PbS NPs) are semiconductor materials that have been widely applied to light-emitting diodes (LEDs), biological fluorescent probes, infrared detection, solar receivers, ion-selective electrodes, and ion-sensitive materials. However, the effects of PbS NPs on the central nervous system are still unclear. Thus, this study aimed to determine, using rats, the mechanism of action of PbS NPs, exposure to which results in persistent alterations in nervous system function. The results of the Morris water maze test showed that PbS NPs significantly impaired learning and memory. Compared with that in the control group, the lead content in the hippocampal tissue was significantly elevated after PbS NP exposure. Exposure to PbS NPs led to increased oxidative damage in blood and hippocampal tissues, and significantly inhibited the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) while increasing the serum malondialdehyde (MDA) content. In addition, reactive oxygen species triggered the activation of Nrf2 and the antioxidant system, including HO-1, r-GCS, and GSH-Px. Moreover, we observed significant apoptosis in the hippocampi of the rats using the TUNEL assay and transmission electron microscopy. The MOD values from the TUNEL assay of the hippocampi were all significantly higher than those of the control group, which increased as the concentration of the PbS NPs increased. There were also changes in the ultrastructure of the hippocampal neurons and synapses in the PbS-treated rats, including a shorter synaptic active zone, smaller curvature of the synaptic interface, and thicker postsynaptic density. Therefore, PbS NP exposure could lead to increased brain lead content, oxidative damage, and apoptosis.
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http://dx.doi.org/10.1039/c9mt00151dDOI Listing
January 2020

Genetical and O-glycoproteomic analyses reveal the roles of three protein O-mannosyltransferases in phytopathogen Fusarium oxysporum f.sp. cucumerinum.

Fungal Genet Biol 2020 01 21;134:103285. Epub 2019 Oct 21.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; National Engineering Research Center for Non-food Bio-refinery, Guangxi Academy of Sciences, Nanning 530007, Guangxi, China. Electronic address:

Protein O-mannosyltransferases (PMTs) have been identified in fungi but not in plants and nematodes, which makes PMTs become attractive targets for developing a new strategy against phytopathogens. Three PMTs have been identified in Fusarium oxysporum, a fungal pathogen that causes vascular wilt in a broad range of economical crops. By deletion or suppression of the pmt genes, we showed that all mutants displayed retarded growth, reduced conidiation, cell wall defects, ER stress and attenuated virulence in F. oxysporum f.sp. cucumerinum. In addition, the Δpmt1 exhibited reduced thermotolerance, while the Δpmt4 and the pmt2 conditional mutant exhibited abnormal polarized growth. Comparative glycoproteome analysis of these pmt mutants revealed that PMTs preferentially modified random coils with flanking regions rich in Ser, Thr, Ala, Glu, Asp and Lys at the stem region of membrane proteins, the N-terminal region close to signal peptide of secreted proteins, or surface of soluble proteins. PMT1 specifically acted on nuclear proteins and proteins that are responsible for protein folding, which might contribute to thermotolerance. PMT4 specifically acted on the membrane and soluble proteins in secretory pathways, especially the GPI anchoring pathway, which might contribute to synthesis and transportation of GPI anchored proteins and thus polarized growth. PMT2 was responsible for modification of proteins that are required for protein folding and cell wall synthesis, which might make PMT2 essential. Our results gave an insight to understanding of the roles of each O-mannosyltransferase in F. oxysporum f.sp. cucumerinum and provide a new perspective to prevent Fusarium wilt.
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http://dx.doi.org/10.1016/j.fgb.2019.103285DOI Listing
January 2020

Ethylene-responsive factor 4 is associated with the desirable rind hardness trait conferring cracking resistance in fresh fruits of watermelon.

Plant Biotechnol J 2020 04 6;18(4):1066-1077. Epub 2019 Nov 6.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou, China.

Fruit rind plays a pivotal role in alleviating water loss and disease and particularly in cracking resistance as well as the transportability, storability and shelf-life quality of the fruit. High susceptibility to cracking due to low rind hardness is largely responsible for severe annual yield losses of fresh fruits such as watermelon in the field and during the postharvest process. However, the candidate gene controlling the rind hardness phenotype remains unclear to date. Herein, we report, for the first time, an ethylene-responsive transcription factor 4 (ClERF4) associated with variation in rind hardness via a combinatory genetic map with bulk segregant analysis (BSA). Strikingly, our fine-mapping approach revealed an InDel of 11 bp and a neighbouring SNP in the ClERF4 gene on chromosome 10, conferring cracking resistance in F populations with variable rind hardness. Furthermore, the concomitant kompetitive/competitive allele-specific PCR (KASP) genotyping data sets of 104 germplasm accessions strongly supported candidate ClERF4 as a causative gene associated with fruit rind hardness variability. In conclusion, our results provide new insight into the underlying mechanism controlling rind hardness, a desirable trait in fresh fruit. Moreover, the findings will further enable the molecular improvement of fruit cracking resistance in watermelon via precisely targeting the causative gene relevant to rind hardness, ClERF4.
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http://dx.doi.org/10.1111/pbi.13276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061880PMC
April 2020

Characterization of watermelon anther and its programmed cell death-associated events during dehiscence under cold stress.

Plant Cell Rep 2019 Dec 28;38(12):1551-1561. Epub 2019 Aug 28.

Laboratory of Germplasm Innovation and Molecular Breeding, College of Agriculture and Biotechnology, Zhejiang University, No. 866 Yuhang Road, Hangzhou, 310058, People's Republic of China.

Key Message: The 'neglected' thermophile fruit crop of watermelon was first used as a model crop to study the PCD associated with anther dehiscence in cold-exposed condition during anther development. Anther dehiscence ensures normal pollen release and successful fertilization at fruit-setting stages in flowering plants. However, most researches pertinent to anther dehiscence are centered on model plant and/or major field crops under optimal growth condition. Due to anther indehiscence in cold condition, crop plants of thermophile tropical or subtropical fruit crops fail to accomplish timely pollination and fertilization, resulting in a great yield loss annually. Herein, we developed an ideal model crop for studying the programmed cell death (PCD) associated with anther dehiscence under low-temperature stress using the S-shaped spiral anther in watermelon as instead. Our results revealed that, including the tapetal cell layers, both cells of the interlocular septum and the stomium were blocked in PCD associated with anther dehiscence at 15 °C. Likewise, TUNEL assays visualized the evidence that low temperature at 15 °C interferes with not only the PCD of tapetal cells, but also the PCD of interlocular septum and stomium. Furthermore, the expressions of genes correlated with PCD of tapetum and stomium were significantly inhibited at 15 °C, suggesting that low temperature affects anther dehiscence by inhibiting PCD of sporophytic tissue-related gene expressions. The findings of the current research provide mechanistic insights into anther indehiscence leading to poor fruit-setting for thermophile fruit crop such as watermelon under adverse cold condition in flowering.
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http://dx.doi.org/10.1007/s00299-019-02466-2DOI Listing
December 2019

AC138128.1 an Intronic lncRNA originating from ERCC1 Implies a Potential Application in Lung Cancer Treatment.

J Cancer 2019 9;10(16):3608-3617. Epub 2019 Jun 9.

Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, P.R. China.

Lung cancer is one of the most devastating tumors with a high incidence and mortality worldwide. Polymorphisms and expression of commonly predicted the occurrence and prognosis of lung cancer. However, few studies have focused on long non-coding RNAs related to though some studies reminded the importance of its post-transcriptional regulation. In the present study, an intronic lncRNA AC138128.1 originated from was firstly identified in microarray chip and database, and its possibility as a novel biomarker to predict lung cancer treatment was further discussed. Firstly, the qRT-PCR data showed that AC138128.1 expression was much lower in lung cancer comparing with its para-cancer tissues, which further analyzed by ROC curve. Similarly, the difference was also verified in 16HBE, A549 and LK cells. Then AC138128.1 expression was found to have an increasing trend in a dose or time-dependent manner after cisplatin treatment. Finally, the subcellular distribution of AC138128.1 reminded that AC138128.1 was mainly expressed in the nucleus. Interestingly a positive relationship between AC138128.1 and expression was only found in cancer tissues, which reminded AC138128.1 may be involved in the regulation of ERCC1. Therefore, as a preliminary exploration of the lncRNA originated from , the present study suggested AC138128.1 is of potential value in predicting platinum analogue benefit in lung cancer.
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http://dx.doi.org/10.7150/jca.31832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636308PMC
June 2019

Epidemic Situation of Brucellosis in Jinzhou City of China and Prediction Using the ARIMA Model.

Can J Infect Dis Med Microbiol 2019 13;2019:1429462. Epub 2019 Jun 13.

Department of Toxicology, School of Public Health, China Medical University, Shenyang 110122, China.

Objective: This study aimed to investigate the specific epidemiological characteristics and epidemic situation of brucellosis in Jinzhou City of China so as to establish a suitable prediction model potentially applied as a decision-supportive tool for reasonably assigning health interventions and health delivery.

Methods: Monthly morbidity data from 2004 to 2013 were selected to construct the autoregressive integrated moving average (ARIMA) model using SPSS 13.0 software. Moreover, stability analysis and sequence tranquilization, model recognition, parameter test, and model diagnostic were also carried out. Finally, the fitting and prediction accuracy of the ARIMA model were evaluated using the monthly morbidity data in 2014.

Results: A total of 3078 cases affected by brucellosis were reported from January 1998 to December 2015 in Jinzhou City. The incidence of brucellosis had shown a fluctuating growth gradually. Moreover, the ARIMA(1,1,1)(0,1,1) model was finally selected among quite a few plausible ARIMA models based upon the parameter test, correlation analysis, and Box-Ljung test. Notably, the incidence from 2005 to 2014 forecasted using this ARIMA model fitted well with the actual incidence data. Notably, the actual morbidity in 2014 fell within the scope of 95% confidence limit of values predicted by the ARIMA(1,1,1)(0,1,1) model, with the absolute error between the predicted and the actual values in 2014 ranging from 0.02 to 0.74. Meanwhile, the MAPE was 19.83%.

Conclusion: It is suitable to predict the incidence of brucellosis in Jinzhou City of China using the ARIMA(1,1,1)(0,1,1) model.
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http://dx.doi.org/10.1155/2019/1429462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595367PMC
June 2019

Lanthanum chloride induces neuron damage by activating the nuclear factor-kappa B signaling pathway in activated microglia.

Metallomics 2019 07;11(7):1277-1287

Department of Toxicology, School of Public Health, China Medical University, No. 77, Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning Province, People's Republic of China.

Lanthanum is a rare earth element which can have adverse effects on the central nervous system (CNS). However, the mechanisms of these effects are not fully understood. The activated microglia plays an important role in the pathogenesis of neurodegenerative diseases and thus could be involved in mediating the toxic effects of lanthanum on the CNS. Nuclear factor-kappa B (NF-κB) is a critical nuclear factor which regulates the expression of inflammatory mediators in the activated microglia. This study investigated the effects of lanthanum chloride (LaCl3) on the NF-κB signaling pathway and explored the relationship between the microglia activation and neuron damage induced by La in vitro. The results showed that BV2 microglial cells treated with 0, 0.05, 0.1 or 0.2 mM LaCl3 could up-regulate the expression of Iba1 protein, a marker of microglia activation, and of p-IKKαβ and p-IκBα in a dose-dependent manner. La could also increase the translocation of the NF-κB p65 subunit from the cytosol into the nucleus, and then elevate the production of NO, TNF-α, IL-1β, IL-6 and MCP-1 by BV2 microglial cells. In a neuron-microglia co-culture system, BV2 microglia treated with LaCl3 resulted in a significant increase of the rates of neuron apoptosis. Conversely, the pre-treatment with PDTC (an inhibitor of the NF-κB signaling pathway) could inhibit the release of inflammatory cytokines and reduce the number of apoptotic neurons caused by La. These findings suggested that the neuron injury induced by LaCl3 might be related to the abnormal activation of microglia, which could remarkably increase the expression and release of pro-inflammatory cytokines via activating the NF-κB signaling pathway.
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http://dx.doi.org/10.1039/c9mt00108eDOI Listing
July 2019
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