Publications by authors named "Chunhai Chen"

74 Publications

NAC antagonizes arsenic-induced neurotoxicity through TMEM179 by inhibiting oxidative stress in Oli-neu cells.

Ecotoxicol Environ Saf 2021 Oct 28;223:112554. Epub 2021 Jul 28.

Department of Occupational Health, Army Medical University, 400038, Chongqing, People's Republic of China. Electronic address:

Arsenic is one of the most common environmental pollutants. Neurotoxicity induced by arsenic has become a major public health concern. However, the effects of arsenic-induced neurotoxicity in the brain and the underlying molecular mechanisms are not well understood. N-acetyl-cysteine (NAC) is a thiol-based antioxidant that can antagonize heavy metal-induced neurotoxicity by scavenging reactive oxygen species (ROS). Here, we used the mouse oligodendrocyte precursor cell (OPC) line Oli-neu to explore the neurotoxic effects of arsenic and the protective effects of NAC. We found that arsenic exposure decreased cell viability, increased oxidative stress, caused mitochondrial dysfunction, and led to apoptosis of Oli-neu cells. Furthermore, we revealed that NAC treatment reversed these neurotoxic effects of arsenic. TMEM179, a key membrane protein, was found highly expressed in OPCs and to be an important factor in maintaining mitochondrial functions. We found that TMEM179 played a critical role in mediating the neurotoxic effects of arsenic and the protective role of NAC. PKCβ is a downstream factor through which TMEM179 regulates the expression of apoptosis-related proteins. This study improves our understanding of the neurotoxic effects and mechanisms of arsenic exposure and the protective effects of NAC. It also identifies a potential molecular target, TMEM179, for the treatment of arsenic-induced neurotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112554DOI Listing
October 2021

Histone hypoacetylation contributes to neurotoxicity induced by chronic nickel exposure in vivo and in vitro.

Sci Total Environ 2021 Aug 10;783:147014. Epub 2021 Apr 10.

Department of Occupational Health, Army Medical University, 400038 Chongqing, People's Republic of China. Electronic address:

Nickel (Ni) is a heavy metal that is both an environmental pollutant and a threat to human health. However, the effects of Ni on the central nervous system in susceptible populations have not been well established. In the present study, the neurotoxicity of Ni and its underlying mechanism were investigated in vivo and in vitro. Ni exposure through drinking water (10 mg Ni/L, 12 weeks) caused learning and memory impairment in mice. Reduced dendrite complexity was observed in both Ni-exposed mouse hippocampi and Ni-treated (200 μM, 72 h) primary cultured hippocampal neurons. The levels of histone acetylation, especially at histone H3 lysine 9 (H3K9ac), were reduced in Ni-exposed mouse hippocampi and cultured neurons. RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing analyses revealed that H3K9ac-modulated gene expression were downregulated. Treatment with sodium butyrate, a histone deacetylase inhibitor, attenuated Ni-induced H3K9 hypoacetylation, neural gene downregulation and dendrite complexity reduction in cultured neurons. Sodium butyrate also restored Ni-induced memory impairment in mice. These results indicate that Ni-induced H3K9 hypoacetylation may be a contributor to the neurotoxicity of Ni. The finding that Ni disturbs histone acetylation in the nervous system may provide new insight into the health risk of chronic Ni exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147014DOI Listing
August 2021

Acupuncture therapy and cognitive dysfunction in patients with type 2 diabetes: A protocol for systematic review.

Medicine (Baltimore) 2021 May;100(21):e26115

Department of Acupuncture and Tuina, Changchun University of Chinese Medicine.

Background: With the aging of society, the incidence of type 2 diabetes (T2DM) is increasing every year, and there is a clear correlation between T2DM and cognitive dysfunction. Acupuncture therapy has been widely used in the treatment of T2DM, but there is no systematic review on the treatment of T2DM associated with cognitive impairment. Therefore, this study aimed to conduct a meta-analysis of acupuncture in the treatment of T2DM with cognitive impairment to clarify its efficacy.

Methods: A structured and systematic literature search will be conducted in the following databases up to April 26, 2021: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (WOS), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific and Journal Database (VIP), and Wan Fang database (Wanfang). We will use the Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures.

Results: This meta-analysis further determined the beneficial effects of acupuncture on T2DM with cognitive impairment.

Conclusion: The purpose of this meta-analysis was to explore the effect of acupuncture on patients T2DM with and cognitive impairment patients, and provide more options for clinicians and patients to treat T2DM with cognitive impairment.

Ethics And Dissemination: This systematics review will evaluate the efficacy and safety of acupuncture in the treatment of T2DM with cognitive impairment. Since all the data included were published, the systematic review did not require ethical approval.

Registration Number: CRD42021245681.
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http://dx.doi.org/10.1097/MD.0000000000026115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154404PMC
May 2021

A Chromosome-Level Assembly of Blunt Snout Bream (Megalobrama amblycephala) Genome Reveals an Expansion of Olfactory Receptor Genes in Freshwater Fish.

Mol Biol Evol 2021 Sep;38(10):4238-4251

College of Fisheries, Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, China.

The number of olfactory receptor genes (ORs), which are responsible for detecting diverse odor molecules varies extensively among mammals as a result of frequent gene gains and losses that contribute to olfactory specialization. However, how OR expansions/contractions in fish are influenced by habitat and feeding habit and which OR subfamilies are important in each ecological niche is unknown. Here, we report a major OR expansion in a freshwater herbivorous fish, Megalobrama amblycephala, using a highly contiguous, chromosome-level assembly. We evaluate the possible contribution of OR expansion to habitat and feeding specialization by comparing the OR repertoire in 28 phylogenetically and ecologically diverse teleosts. In total, we analyzed > 4,000 ORs including 3,253 intact, 122 truncated, and 913 pseudogenes. The number of intact ORs is highly variable ranging from 20 to 279. We estimate that the most recent common ancestor of Osteichthyes had 62 intact ORs, which declined in most lineages except the freshwater Otophysa clade that has a substantial expansion in subfamily β and ε ORs. Across teleosts, we found a strong association between duplications of β and ε ORs and freshwater habitat. Nearly, all ORs were expressed in the olfactory epithelium (OE) in three tested fish species. Specifically, all the expanded β and ε ORs were highly expressed in OE of M. amblycephala. Together, we provide molecular and functional evidence for how OR repertoires in fish have undergone gain and loss with respect to ecological factors and highlight the role of β and ε OR in freshwater adaptation.
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http://dx.doi.org/10.1093/molbev/msab152DOI Listing
September 2021

1800 MHz Radiofrequency Electromagnetic Field Impairs Neurite Outgrowth Through Inhibiting EPHA5 Signaling.

Front Cell Dev Biol 2021 12;9:657623. Epub 2021 Apr 12.

Department of Occupational Health, Third Military Medical University, Chongqing, China.

The increasing intensity of environmental radiofrequency electromagnetic fields (RF-EMF) has increased public concern about its health effects. Of particular concern are the influences of RF-EMF exposure on the development of the brain. The mechanisms of how RF-EMF acts on the developing brain are not fully understood. Here, based on high-throughput RNA sequencing techniques, we revealed that transcripts related to neurite development were significantly influenced by 1800 MHz RF-EMF exposure during neuronal differentiation. Exposure to RF-EMF remarkably decreased the total length of neurite and the number of branch points in neural stem cells-derived neurons and retinoic acid-induced Neuro-2A cells. The expression of Eph receptors 5 (EPHA5), which is required for neurite outgrowth, was inhibited remarkably after RF-EMF exposure. Enhancing EPHA5 signaling rescued the inhibitory effects of RF-EMF on neurite outgrowth. Besides, we identified that cAMP-response element-binding protein (CREB) and RhoA were critical downstream factors of EPHA5 signaling in mediating the inhibitory effects of RF-EMF on neurite outgrowth. Together, our finding revealed that RF-EMF exposure impaired neurite outgrowth through EPHA5 signaling. This finding explored the effects and key mechanisms of how RF-EMF exposure impaired neurite outgrowth and also provided a new clue to understanding the influences of RF-EMF on brain development.
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http://dx.doi.org/10.3389/fcell.2021.657623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075058PMC
April 2021

The evolution of ancestral and species-specific adaptations in snowfinches at the Qinghai-Tibet Plateau.

Proc Natl Acad Sci U S A 2021 Mar;118(13)

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China;

Species in a shared environment tend to evolve similar adaptations under the influence of their phylogenetic context. Using snowfinches, a monophyletic group of passerine birds (Passeridae), we study the relative roles of ancestral and species-specific adaptations to an extreme high-elevation environment, the Qinghai-Tibet Plateau. Our ancestral trait reconstruction shows that the ancestral snowfinch occupied high elevations and had a larger body mass than most nonsnowfinches in Passeridae. Subsequently, this phenotypic adaptation diversified in the descendant species. By comparing high-quality genomes from representatives of the three phylogenetic lineages, we find that about 95% of genes under positive selection in the descendant species are different from those in the ancestor. Consistently, the biological functions enriched for these species differ from those of their ancestor to various degrees (semantic similarity values ranging from 0.27 to 0.5), suggesting that the three descendant species have evolved divergently from the initial adaptation in their common ancestor. Using a functional assay to a highly selective gene, , we demonstrate that the nonsynonymous substitutions in the ancestor and descendant species have improved the repair capacity of ultraviolet-induced DNA damage. The repair kinetics of the gene shows a twofold to fourfold variation across the ancestor and the descendants. Collectively, this study reveals an exceptional case of adaptive evolution to high-elevation environments, an evolutionary process with an initial adaptation in the common ancestor followed by adaptive diversification of the descendant species.
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http://dx.doi.org/10.1073/pnas.2012398118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020664PMC
March 2021

3D Printing of Lightweight Polyimide Honeycombs with the High Specific Strength and Temperature Resistance.

ACS Appl Mater Interfaces 2021 Apr 10;13(13):15690-15700. Epub 2021 Mar 10.

Key Laboratory of High Performance Plastics (Jilin University), Ministry of Education, National & Local Joint Engineering Laboratory for Synthesis Technology of High Performance Polymer, College of Chemistry, Jilin University, Changchun 130012, China.

Lightweight structures are often used for applications requiring higher strength-to-weight ratios and lower densities, such as in aircraft, vehicles, and various engine components. Three-dimensional (3D) printing technology has been widely used for lightweight polymer structures because of the superior flexibility, personalized design, and ease of operation offered by it. However, synthesis of lightweight polymeric structures that possess both high specific strength and glass transfer temperature () remains an elusive goal, because 3D printed polymers with these properties are still very few in the market. For example, 3,3',4,4'-biphenyl tetracarboxylic dianhydride (BPDA) and -phenylenediamine (PDA)-type (UPILEX-S type) polyimides show exceptional thermal stability ( up to ≈400 °C) and mechanical properties (tensile strength exceeding 500 MPa) and are the first choice if extremely high temperatures of 400 °C or even higher (depending on the duration) are required, which hampers their processing using existing 3D printing techniques. However, their processing using existing 3D printing techniques is hampered due to their thermal resistance. Herein, a 3D printing approach was demonstrated for generating complex lightweight BPDA-PDA polyimide geometries with unprecedented specific strength and thermal resistance. The simple aqueous polymerization reaction of BPDA with water-soluble PDA and triethylamine (TEA) afforded the poly(amic acid) ammonium salt (PAAS) hydrogels. These PAAS solutions showed clear shear thinning and thermo-reversibility, along with high ' gel-state moduli, which ensured self-supporting features and shape fidelity in the gel state. Postprinting thermal treatment transformed the PAAS precursor to BPDA-PDA polyimide (UPILEX-S type). The resulting layer-by-layer deposition onto lightweight polyimide honeycombs in the form of triangular, square, and hexagonal structures showed tailorable mechanical strength, exceptional compressive strength-to-weight ratio (highest up to 0.127 MPa (kg m)), and remarkable thermoresistance ( approximately 380 °C). These high-performance 3D printed polyimide honeycombs and unique synthetic techniques with general structures are potentially useful in fields ranging from automotive to aerospace technologies.
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http://dx.doi.org/10.1021/acsami.1c01992DOI Listing
April 2021

In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury.

Cell Stem Cell 2021 05 5;28(5):923-937.e4. Epub 2021 Mar 5.

Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

Adult neurogenesis plays critical roles in maintaining brain homeostasis and responding to neurogenic insults. However, the adult mammalian spinal cord lacks an intrinsic capacity for neurogenesis. Here we show that spinal cord injury (SCI) unveils a latent neurogenic potential of NG2+ glial cells, which can be exploited to produce new neurons and promote functional recovery after SCI. Although endogenous SOX2 is required for SCI-induced transient reprogramming, ectopic SOX2 expression is necessary and sufficient to unleash the full neurogenic potential of NG2 glia. Ectopic SOX2-induced neurogenesis proceeds through an expandable ASCL1+ progenitor stage and generates excitatory and inhibitory propriospinal neurons, which make synaptic connections with ascending and descending spinal pathways. Importantly, SOX2-mediated reprogramming of NG2 glia reduces glial scarring and promotes functional recovery after SCI. These results reveal a latent neurogenic potential of somatic glial cells, which can be leveraged for regenerative medicine.
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http://dx.doi.org/10.1016/j.stem.2021.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106641PMC
May 2021

Novel TiO Nanoparticles/Polysulfone Composite Hollow Microspheres for Photocatalytic Degradation.

Polymers (Basel) 2021 Jan 21;13(3). Epub 2021 Jan 21.

Center for Advanced Low-Dimension Materials, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.

Nanosized titanium oxide (TiO) material is a promising photocatalyst for the degradation of organic pollutants, whereas the difficulty of its recycling hinders its practical application. Herein, we reported the preparation of a novel titanium oxide/polysulfone (TiNPs/PSF) composite hollow microspheres by the combination of Pickering emulsification and the solvent evaporation technique and their application for the photodegradation of methyl blue (MB). P25 TiO nanoparticles dispersed on the surface of PSF microspheres. The porosity, density and photoactivity of the TiNPs/PSF composite microsphere are influenced by the TiO loading amount. The composite microsphere showed good methyl blue (MB) removal ability. Compared with TiO P25, and PSF, a much higher MB adsorption speed was observed for TiNPs/PSF microspheres benefited from their porous structure and the electrostatic attractions between the MB+ and the negatively charged PSF materials, and showed good degradation efficiency. For TiNPs/PSF composite microsphere with density close to 1, a 100% MB removal (10 mg L) within 120 min at a catalyst loading of 2.5 g L can be obtained under both stirring and static condition, due to well dispersing of TiO particles on the microsphere surface and its stable suspending in water. For the non-suspended TiNPs/PSF composite microsphere with density bigger than 1, the 100% MB removal can be only obtained under stirring condition. The removal efficiency of MB for the composite microspheres retained 96.5%, even after 20 cycles. Moreover, this composite microsphere also showed high MB removal ability at acidic condition. The high catalysis efficiency, excellent reusability and good stability make this kind of TiNPs/PSF composite microsphere a promising photocatalyst for the water organic pollution treatment.
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http://dx.doi.org/10.3390/polym13030336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865213PMC
January 2021

BIX-01294, a G9a inhibitor, suppresses cell proliferation by inhibiting autophagic flux in nasopharyngeal carcinoma cells.

Invest New Drugs 2021 Jun 2;39(3):686-696. Epub 2021 Jan 2.

Department of Otolaryngology Head and Neck Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

G9a, a histone methyltransferase, has been found to be upregulated in a range of tumor tissues, and contributes to tumor growth and metastasis. However, the impact of G9a inhibition as a potential therapeutic target in nasopharyngeal carcinoma (NPC) is unclear. In the present study we aimed to investigate the anti-proliferative effect of G9a inhibition in the NPC cell lines CNE1 and CNE2, and to further elucidate the molecular mechanisms underlying these effects. The expression of G9a in NPC tumor tissues was significantly higher than that in normal nasopharyngeal tissues. The pharmacological inhibition of G9a by BIX-01294 (BIX) inhibited proliferation and induced caspase-independent apoptosis in NPC cells in vitro. Treatment with BIX induced autophagosome accumulation, which exacerbated the cytotoxic activity of BIX in NPC cells. Mechanistic studies have found that BIX impairs autophagosomes by initiating autophagy in a Beclin-1-independent way, and impairs autophagic degradation by inhibiting lysosomal cathepsin D activation, leading to lysosomal dysfunction. BIX was able to suppress tumor growth, possibly by inhibiting autophagic flux; it might therefore constitute a promising candidate for NPC therapy.
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http://dx.doi.org/10.1007/s10637-020-01053-7DOI Listing
June 2021

Bisphenol A promotes breast cancer cell proliferation by driving miR-381-3p-PTTG1-dependent cell cycle progression.

Chemosphere 2021 Apr 15;268:129221. Epub 2020 Dec 15.

Department of Environmental Medicine, School of Public Health, and Department of Emergency Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, China. Electronic address:

Bisphenol A (BPA) is a high-production-volume industrial chemical that facilitates the development of breast cancer. However, the molecular mechanism associated with BPA-induced breast cancer cell proliferation and migration remains elusive. In our study, we exposed MCF-7 cells to different concentrations of BPA (0.1, 1 and 10 μM) for 24, 48, or 72 h. We found that BPA exposure significantly promoted MCF-7 cell proliferation and migration but not invasion. To elucidate the mechanisms, the differentially expressed genes between the BPA and control groups were investigated with the Gene Expression Omnibus (GEO) database through GEO2R. Kyoto Encyclopedia of Genes and Genomes (KEGG) and pathway action network analyses demonstrated the important role of the cell cycle pathway in the effects of BPA exposure on MCF-7 cells. Importantly, analysis with the cytoHubba plugin of Cytoscape software coupled with analysis of enriched genes in the cell cycle pathway identified PTTG1 and CDC20 (two hub genes) as key targets associated with BPA-induced MCF-7 cell proliferation and migration. Interestingly, BPA significantly increased the protein expression levels of PTTG1 but not CDC20. Knockdown of PTTG1 inhibited the BPA-induced increase in proliferation and maintained cell cycle progression. In addition, we confirmed that the increased expression of PTTG1 upon BPA exposure was caused by miR-381-3p inhibition. Moreover, we verified that miR-381-3p expression was low and inversely correlated with PTTG1 expression in breast cancer tissues. Together, these findings demonstrate that BPA promotes high PTTG1 expression and alters the cell cycle to enhance MCF-7 cell proliferation by inhibiting miR-381-3p expression.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129221DOI Listing
April 2021

Fabrication of ultrafiltration membranes by poly (aryl ether nitrile) with poly (ethylene glycol) as additives.

Water Sci Technol 2020 Dec;82(12):2847-2856

Center for Advanced Low-Dimension Materials, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Material Science and Engineering, Donghua University, Shanghai 201620, China E-mail:

A new kind of flat sheet ultrafiltration membrane was prepared by a promising membrane material, poly (aryl ether nitrile) (PEN), via non-solvent induced phase separation. The effect of solvents, N-methyl-2-pyrrolidone (NMP) and dimethyl acetamide (DMAc), as well as additive of poly (ethylene glycol) (PEG) with different molecular weights on the structure and permeation performance of synthesized membranes were investigated. Comparing with NMP, DMAc is more suitable for the casting solution preparation due to better solubility. A gradually changing pore from sponge-like to finger-like can be observed when PEG was added with DMAc as solvent, while a finger-like pore structure always appears in the NMP system with or without PEG. In both systems, the formation of macrovoids is effectively promoted by the addition of PEG, and higher porosity membranes can be obtained by PEG with higher molecular weight. With the increase of PEG molecular weight from 400 to 10,000 Da, the permeate flux increases from 74.5 to 114.3 L·m·h and from 102.0 to 130.8 L·m·h under a 100 kPa pressure-driven when NMP and DMAc were used as solvents, respectively. The membranes prepared by DMAc exhibit outstanding rejection of BSA with rejections all above 96.5%.
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http://dx.doi.org/10.2166/wst.2020.529DOI Listing
December 2020

Long-term bisphenol A exposure exacerbates diet-induced prediabetes via TLR4-dependent hypothalamic inflammation.

J Hazard Mater 2021 01 14;402:123926. Epub 2020 Sep 14.

Department of Environmental Medicine, and Department of Emergency Medicine of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China. Electronic address:

Bisphenol A (BPA), an environmental endocrine-disrupting compound, has been revealed associated with metabolic disorders such as obesity, prediabetes, and type 2 diabetes (T2D). However, its underlying mechanisms are still not fully understood. Here, we provide new evidence that BPA is a risk factor for T2D from a case-control study. To explore the detailed mechanisms, we used two types of diet models, standard diet (SD) and high-fat diet (HFD), to study the effects of long-term BPA exposure on prediabetes in 4-week-old mice. We found that BPA exposure for 12 weeks exacerbated HFD-induced prediabetic symptoms. Female mice showed increased body mass, serum insulin level, and impaired glucose tolerance, while male mice only exhibited impaired glucose tolerance. No change was found in SD-fed mice. Besides, BPA exposure enhanced astrocyte-dependent hypothalamic inflammation in both male and female mice, which impaired proopiomelanocortin (POMC) neuron functions. Moreover, eliminating inflammation by toll-like receptor 4 (TLR4) knockout significantly abolished the effects of BPA on the hypothalamus and diet-induced prediabetes. Taken together, our data establish a key role for TLR4-dependent hypothalamic inflammation in regulating the effects of BPA on prediabetes.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123926DOI Listing
January 2021

Dual-Switching Electrochromism and Electrofluorochromism Derived from Diphenylamine-Based Polyamides with Spirobifluorene/Pyrene as Bridged Fluorescence Units.

ACS Appl Mater Interfaces 2020 May 4;12(19):22099-22107. Epub 2020 May 4.

Center for Advanced Low-Dimension Materials, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201600, China.

Electrochromic (EC)/electrofluorochromic (EFC) bifunctional materials are receiving great attention because of their promising applications in optoelectronic devices. However, the development of ideal EC/EFC bifunctional materials is still a great challenge because of the poor integration of EC/EFC performances (optical contrast, response speed, and switching stability). Herein, we reported two novel diphenylamine-based mixed valence (MV) polyamides (S-HPA and P-HPA) with spirobifluorene (2,7-positions) and pyrene (1,6-positions) as bridged fluorescence units, respectively, showing impressive cyclability and fluorescence contrast with rapid switching. Through the formation of an effective electronic coupling between the two nitrogen centers using spirobifluorene/pyrene bridges, we demonstrated that different bridges have significant effects on the thermal and electrooptical characteristics of polyamides. In addition to lower fluorescence quantum yield and glass transition temperature, the S-HPA exhibited superior cyclability (contrast change <3.4%/14% over 500/300 cycles for EC/EFC switching), higher color/fluorescence contrast (64%/304%), and faster switching time (<2.6 s), mainly owing to the shorter conjugated length and more twisted configuration of the spirobifluorene bridge. The design principle of MV polymers with fluorophore bridges proposed here will be a promising way to realize high-performance EC/EFC devices and will also provide new insights into their future development and applications.
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http://dx.doi.org/10.1021/acsami.0c01021DOI Listing
May 2020

KIF5A-dependent axonal transport deficiency disrupts autophagic flux in trimethyltin chloride-induced neurotoxicity.

Autophagy 2021 04 30;17(4):903-924. Epub 2020 Mar 30.

Department of Environmental Medicine, and Department of Emergency Medicine of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Trimethyltin chloride (TMT) is widely used as a constituent of fungicides and plastic stabilizers in the industrial and agricultural fields, and is generally acknowledged to have potent neurotoxicity, especially in the hippocampus; however, the mechanism of induction of neurotoxicity by TMT remains elusive. Herein, we exposed Neuro-2a cells to different concentrations of TMT (2, 4, and 8 μM) for 24 h. Proteomic analysis, coupled with bioinformatics analysis, revealed the important role of macroautophagy/autophagy-lysosome machinery in TMT-induced neurotoxicity. Further analysis indicated significant impairment of autophagic flux by TMT via suppressed lysosomal function, such as by inhibiting lysosomal proteolysis and changing the lysosomal pH, thereby contributing to defects in autophagic clearance and subsequently leading to nerve cell death. Mechanistically, molecular interaction networks of Ingenuity Pathway Analysis identified a downregulated molecule, KIF5A (kinesin family member 5A), as a key target in TMT-impaired autophagic flux. TMT decreased KIF5A protein expression, disrupted the interaction between KIF5A and lysosome, and impaired lysosomal axonal transport. Moreover, overexpression restored axonal transport, increased lysosomal dysfunction, and antagonized TMT-induced neurotoxicity . Importantly, in TMT-administered mice with seizure symptoms and histomorphological injury in the hippocampus, TMT inhibited KIF5A expression in the hippocampus. Gene transfer of enhanced autophagic clearance in the hippocampus and alleviated TMT-induced neurotoxicity . Our results are the first to demonstrate KIF5A-dependent axonal transport deficiency to cause autophagic flux impairment via disturbance of lysosomal function in TMT-induced neurotoxicity; manipulation of KIF5A may be a therapeutic approach for antagonizing TMT-induced neurotoxicity.: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTB: actin beta; AGC: automatic gain control; ATG: autophagy-related; ATP6V0D1: ATPase H transporting lysosomal V0 subunit D1; ATP6V1E1: ATPase H transporting lysosomal V1 subunit E1; CA: cornu ammonis; CQ: chloroquine; CTSB: cathepsin B; CTSD: cathepsin D; DCTN1: dynactin subunit 1; DG: dentate gyrus; DYNLL1: dynein light chain LC8-type 1; FBS: fetal bovine serum; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor associated protein like 1; GABARAPL2: GABA type A receptor associated protein like 2; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; IPA: Ingenuity Pathway Analysis; KEGG: Kyoto Encyclopedia of Genes and Genomes; KIF5A: kinesin family member 5A; LAMP: lysosomal-associated membrane protein; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; PBS: phosphate-buffered saline; PFA: paraformaldehyde; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PRM: parallel reaction monitoring; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; SYP: synaptophysin; TAX1BP1: Tax1 binding protein 1; TMT: trimethyltin chloride; TUB: tubulin.
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http://dx.doi.org/10.1080/15548627.2020.1739444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078766PMC
April 2021

Synthesis of Superheat-Resistant Polyimides with Enhanced Dielectric Constant by Introduction of Cu(ΙΙ)-Coordination.

Polymers (Basel) 2020 Feb 13;12(2). Epub 2020 Feb 13.

Center for Advanced Low-Dimension Materials, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Material Science and Engineering, Donghua University, Shanghai 201620, China.

To achieve polyimide-metal complexes with enhanced properties, 5-amine-2-(5-aminopyridin-2-yl)-1-methyl-benzimidazole (PyMePABZ) that contains stiff 2-(2'-pyridyl)benzimidazole (PyBI) was synthesized and exploited to construct the Cu(ΙΙ)-crosslinked polyimides (Cu-PIs). These Cu-PIs exhibited higher dielectric, thermal, and mechanical properties with an increase in Cu content. Among them, their dielectric constants (ε) were up to 43% superior to that of the neat PI, glass transition temperatures (Ts) were all over 400 °C, and 5% weight loss temperature (T) maintained beyond 500 °C. These data indicate that the metal coordination crosslinking provided a useful guide to develop high performance PIs which possess potential application as useful high temperature capacitors.
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http://dx.doi.org/10.3390/polym12020442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077670PMC
February 2020

Transcriptomic insight into cadmium-induced neurotoxicity in embryonic neural stem/progenitor cells.

Toxicol In Vitro 2020 Feb 12;62:104686. Epub 2019 Oct 12.

Department of Environmental Medicine, School of Public Health, and Department of Emergency Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, China. Electronic address:

Cadmium exposure has raised great public concern. Extensive studies have revealed the neurotoxic effects of cadmium exposure during brain development. However, more evidence is still needed to reach a consistent conclusion and uncover the underlying mechanisms. Here, we used primary mouse embryonic neural stem/progenitor cells (NSPCs) as a cell model and exposed the cells to 0, 1, 2 or 4 μM cadmium. High-throughput mRNA-seq technology was used to explore the global transcriptome changes in NSPCs after exposure to 2 μM cadmium. We found that cadmium exposure remarkably influenced the expression of genes involved in cell growth, proliferation, cell cycle and survival. Pathway-Act-Network analysis revealed that these altered genes were targeted to the P53, PI3K-AKT, MAPK, calcium, and NF-kappa B signaling pathways. In vitro experiments using cultured NSPCs verified that cadmium exposure reduced cell viability, proliferation, neurosphere formation and caused cell cycle arrest at low concentrations (≤ 2 μM), while induced cell apoptosis at high concentrations (≥ 4 μM). Real-time PCR results confirmed the concentration-dependent effects of cadmium exposure on the expression of critical genes in the above signaling pathways. Together, our results provide transcriptomic insight into cadmium-induced developmental neurotoxic effects and the underlying mechanisms.
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http://dx.doi.org/10.1016/j.tiv.2019.104686DOI Listing
February 2020

Inhibition of SERPINA3N-dependent neuroinflammation is essential for melatonin to ameliorate trimethyltin chloride-induced neurotoxicity.

J Pineal Res 2019 Oct 6;67(3):e12596. Epub 2019 Aug 6.

Department of Environmental Medicine, and Department of Emergency Medicine of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Trimethyltin chloride (TMT) is a potent neurotoxin that causes neuroinflammation and neuronal cell death. Melatonin is a well-known anti-inflammatory agent with significant neuroprotective activity. Male C57BL/6J mice were intraperitoneally injected with a single dose of melatonin (10 mg/kg) before exposure to TMT (2.8 mg/kg, ip). Thereafter, the mice received melatonin (10 mg/kg, ip) once a day for another three consecutive days. Melatonin dramatically alleviated TMT-induced neurotoxicity in mice by attenuating hippocampal neuron loss, inhibiting epilepsy-like seizures, and ameliorating memory deficits. Moreover, melatonin markedly suppressed TMT-induced neuroinflammatory responses and astrocyte activation, as shown by a decrease in inflammatory cytokine production as well as the downregulation of neurotoxic reactive astrocyte phenotype markers. Mechanistically, serine peptidase inhibitor clade A member 3N (SERPINA3N) was identified as playing a central role in the protective effects of melatonin based on quantitative proteome and bioinformatics analysis. Most importantly, melatonin significantly suppressed TMT-induced SERPINA3N upregulation at both the mRNA and protein levels. The overexpression of Serpina3n in the mouse hippocampus abolished the protective effects of melatonin on TMT-induced neuroinflammation and neurotoxicity. Melatonin protected cells against TMT-induced neurotoxicity by inhibiting SERPINA3N-mediated neuroinflammation. Melatonin may be a promising and practical agent for reducing TMT-induced neurotoxicity in clinical practice.
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http://dx.doi.org/10.1111/jpi.12596DOI Listing
October 2019

Soluble Polyimides Bearing ()-Hydrogenated Bisphenol A and ()-Hydrogenated Bisphenol A Moieties: Synthesis, Properties and the Conformational Effect.

Polymers (Basel) 2019 May 10;11(5). Epub 2019 May 10.

Key Laboratory of High Performance Plastics (Jilin University), Ministry of Education. National & Local Joint Engineering Laboratory for Synthesis Technology of High Performance Polymer. College of Chemistry, Jilin University, Changchun 130012, China.

In this work, hydrogenated bisphenol A (HBPA) based dinitro mixed isomers (1a' and 1a) were synthesized and separated via vacuum distillation under the monitor of DSC and H NMR. Corresponding diamines (2a' and 2a) were separately polycondensed with five commercial dianhydrides via a two-step thermal imidization to obtain PI-(1'-5') and PI-(1-5). All the polyimides could afford flexible, tough, and transparent films, and most of them were readily soluble not only in common polar solvents like DMAc, but also in low boiling point solvents such as chloroform. H NMR spectra of the polyimides demonstrated that HBPA moiety showed no conformation changes during the preparation of polymers. For a given dianhydride, PI-(1-5) exhibited better thermal stability than that of PI-(1'-5'), this can be attributed that the C-O in PI-(1-5) promoted denser and more regular molecular chain stacking, as can be evidenced by the WAXD and geometric optimization results. Additionally, when the dianhydride was ODPA, BPADA or 6FDA, no apparent difference was found in either the transmittance or solubility between two series of polyimides, which could be attributed that twisted and flexible ether linkages, as well as bulky substituents, led to the "already weakened" inter- and intramolecular CT interaction and cohesive force. However, when it came to rigid and stiff dianhydride, e.g., BPDA, PI-3' took an obvious advantage over PI-3 in transmittance and solubility, which was possibly owed to the larger molecular chain d-spacing imparted by C-O. An overall investigation of PI-(1'-5') and PI-(1-5) on aspects of thermal, mechanical, morphological, soluble and optical performance values was carried out, and the conformation effects of HBPA isomers on the properties of two series of polyimides were discussed in detail.
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http://dx.doi.org/10.3390/polym11050854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571896PMC
May 2019

Draft genome of the river water buffalo.

Ecol Evol 2019 Mar 18;9(6):3378-3388. Epub 2019 Feb 18.

Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Buffalo Research Institute Chinese Academy of Agricultural Sciences Nanning China.

Water buffalo (), a large-sized member of the Bovidae family, is considered as an important livestock species throughout Southeast Asia. In order to better understand the molecular basis of buffalo improvement and breeding, we sequenced and assembled the genome (2n=50) of a river buffalo species from Bangladesh. Its genome size is 2.77 Gb, with a contig N50 of 25 kb and the scaffold N50 of 6.9 Mbp. Based on the assembled genome, we annotated 24,613 genes for future functional genomics studies. Phylogenetic tree analysis of cattle and water buffalo lineages showed that they diverged about 5.8-9.8 million years ago. Our findings provide an insight into the water buffalo genome which will contribute in further research on buffalo such as molecular breeding, understanding complex traits, conservation, and biodiversity.
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http://dx.doi.org/10.1002/ece3.4965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434576PMC
March 2019

Genome structure and evolution of Antirrhinum majus L.

Nat Plants 2019 02 28;5(2):174-183. Epub 2019 Jan 28.

National Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Snapdragon (Antirrhinum majus L.), a member of the Plantaginaceae family, is an important model for plant genetics and molecular studies on plant growth and development, transposon biology and self-incompatibility. Here we report a near-complete genome assembly of A. majus cultivar JI7 (A. majus cv.JI7) comprising 510 Megabases (Mb) of genomic sequence and containing 37,714 annotated protein-coding genes. Scaffolds covering 97.12% of the assembled genome were anchored on eight chromosomes. Comparative and evolutionary analyses revealed that a whole-genome duplication event occurred in the Plantaginaceae around 46-49 million years ago (Ma). We also uncovered the genetic architectures associated with complex traits such as flower asymmetry and self-incompatibility, identifying a unique duplication of TCP family genes dated to around 46-49 Ma and reconstructing a near-complete ψS-locus of roughly 2 Mb. The genome sequence obtained in this study not only provides a representative genome sequenced from the Plantaginaceae but also brings the popular plant model system of Antirrhinum into the genomic age.
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http://dx.doi.org/10.1038/s41477-018-0349-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784882PMC
February 2019

AKT inhibition-mediated dephosphorylation of TFE3 promotes overactive autophagy independent of MTORC1 in cadmium-exposed bone mesenchymal stem cells.

Autophagy 2019 04 20;15(4):565-582. Epub 2018 Oct 20.

a Department of Environmental Medicine, and Department of Critical Care Medicine of the First Affiliated Hospital , Zhejiang University School of Medicine , Hangzhou , China.

Cadmium (Cd) is a toxic metal that is widely found in numerous environmental matrices and induces serious adverse effects in various organs and tissues. Bone tissue seems to be a crucial target of Cd contamination. Macroautophagy/autophagy has been proposed to play a pivotal role in Cd-mediated bone toxicity. However, the mechanisms that underlie Cd-induced autophagy are not yet completely understood. We demonstrated that Cd treatment increased autophagic flux and inhibition of the autophagic process using Atg7 gene silencing blocked the Cd-induced mesenchymal stem cell death. Mechanistically, Cd activated nuclear translocation of TFE3 but not that of TFEB or MITF, which contributed to the expression of autophagy-related genes and lysosomal biogenesis. Specifically, Cd decreased expression of phospho-AKT (Ser473). The reduction in AKT activity led to dephosphorylation of cytosolic TFE3 at Ser565 and promoted TFE3 nuclear translocation independently of MTORC1. Notably, Cd treatment increased the activity of PPP3/calcineurin, and pharmacological inhibition of PPP3/calcineurin with FK506 suppressed AKT dephosphorylation and TFE3 activity. These results suggest that PPP3/calcineurin negatively regulates AKT phosphorylation and is involved in Cd-induced TFE3-dependent autophagy. Modulation of the PPP3/calcineurin-AKT-TFE3 autophagic-lysosomal machinery may offer novel therapeutic approaches for the treatment of Cd-induced bone damage. Abbreviations: ACTB: actin: beta; AKT: thymoma viral proto-oncogene; AMPK: AMP-activated protein kinase; ATG: autophagy related; Baf A1: bafilomycin A; Cd: cadmium; FOXO3: forkhead box O3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MITF: melanogenesis associated transcription factor; MSC: mesenchymal stem sell; MTORC1: mechanistic target of rapamycin kinase complex 1; RPS6KB1: ribosomal protein S6 kinase: polypeptide 1; SGK1: serum/glucocorticoid regulated kinase 1; SQSTM1/p62: sequestosome 1;TFE3: transcription factor E3; TFEB: transcription factor EB; TFEC: transcription factor EC.
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http://dx.doi.org/10.1080/15548627.2018.1531198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526814PMC
April 2019

Chromosome-level reference genome and alternative splicing atlas of moso bamboo (Phyllostachys edulis).

Gigascience 2018 10 1;7(10). Epub 2018 Oct 1.

State Forestry Administration Key Open Laboratory on the Science and Technology of Bamboo and Rattan, Institute of Gene Science for Bamboo and Rattan Resources, International Center for Bamboo and Rattan, Futongdong Rd, WangJing, Chaoyang District Beijing 100102, China.

Background: Bamboo is one of the most important nontimber forestry products worldwide. However, a chromosome-level reference genome is lacking, and an evolutionary view of alternative splicing (AS) in bamboo remains unclear despite emerging omics data and improved technologies.

Results: Here, we provide a chromosome-level de novo genome assembly of moso bamboo (Phyllostachys edulis) using additional abundance sequencing data and a Hi-C scaffolding strategy. The significantly improved genome is a scaffold N50 of 79.90 Mb, approximately 243 times longer than the previous version. A total of 51,074 high-quality protein-coding loci with intact structures were identified using single-molecule real-time sequencing and manual verification. Moreover, we provide a comprehensive AS profile based on the identification of 266,711 unique AS events in 25,225 AS genes by large-scale transcriptomic sequencing of 26 representative bamboo tissues using both the Illumina and Pacific Biosciences sequencing platforms. Through comparisons with orthologous genes in related plant species, we observed that the AS genes are concentrated among more conserved genes that tend to accumulate higher transcript levels and share less tissue specificity. Furthermore, gene family expansion, abundant AS, and positive selection were identified in crucial genes involved in the lignin biosynthetic pathway of moso bamboo.

Conclusions: These fundamental studies provide useful information for future in-depth analyses of comparative genome and AS features. Additionally, our results highlight a global perspective of AS during evolution and diversification in bamboo.
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http://dx.doi.org/10.1093/gigascience/giy115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204424PMC
October 2018

The chromosome-level genome assemblies of two rattans (Calamus simplicifolius and Daemonorops jenkinsiana).

Gigascience 2018 09 1;7(9). Epub 2018 Sep 1.

State Forestry Administration Key Open Laboratory on the Science and Technology of Bamboo and Rattan, Institute of Gene Science for Bamboo and Rattan Resources, International Center for Bamboo and Rattan, Futongdong Rd, WangJing, Chaoyang District, Beijing 100102, China.

Background: Calamus simplicifolius and Daemonorops jenkinsiana are two representative rattans, the most significant material sources for the rattan industry. However, the lack of reference genome sequences is a major obstacle for basic and applied biology on rattan.

Findings: We produced two chromosome-level genome assemblies of C. simplicifolius and D. jenkinsiana using Illumina, Pacific Biosciences, and Hi-C sequencing data. A total of ∼730 Gb and ∼682 Gb of raw data covered the predicted genome lengths (∼1.98 Gb of C. simplicifolius and ∼1.61 Gb of D. jenkinsiana) to ∼372 × and ∼426 × read depths, respectively. The two de novo genome assemblies, ∼1.94 Gb and ∼1.58 Gb, were generated with scaffold N50s of ∼160 Mb and ∼119 Mb in C. simplicifolius and D. jenkinsiana, respectively. The C. simplicifolius and D. jenkinsiana genomes were predicted to harbor  51,235 and  53,342 intact protein-coding gene models, respectively. Benchmarking Universal Single-Copy Orthologs evaluation demonstrated that genome completeness reached 96.4% and 91.3% in the C. simplicifolius and D. jenkinsiana genomes, respectively. Genome evolution showed that four Arecaceae plants clustered together, and the divergence time between the two rattans was ∼19.3 million years ago. Additionally, we identified 193 and 172 genes involved in the lignin biosynthesis pathway in the C. simplicifolius and D. jenkinsiana genomes, respectively.

Conclusions: We present the first de novo assemblies of two rattan genomes (C. simplicifolius and D. jenkinsiana). These data will not only provide a fundamental resource for functional genomics, particularly in promoting germplasm utilization for breeding, but also serve as reference genomes for comparative studies between and among different species.
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http://dx.doi.org/10.1093/gigascience/giy097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117794PMC
September 2018

AIE-Active Polyamide Containing Diphenylamine-TPE Moiety with Superior Electrofluorochromic Performance.

ACS Appl Mater Interfaces 2018 May 24;10(18):16105-16112. Epub 2018 Apr 24.

Key Laboratory of High Performance Plastics (Jilin University), Ministry of Education, National & Local Joint Engineering Laboratory for Synthesis Technology of High Performance Polymer, College of Chemistry , Jilin University , Changchun 130012 , PR China.

Electrofluorochromism has attracted great attention due to the intelligence optoelectronic and sensing applications. The intrinsically switchable fluorophores with high solid-state fluorescence are regarded as key for ideal electrofluorochromic materials. Here, we reported an AIE-active polyamide with diphenylamine and tetraphenylethylene units, showing high fluorescence quantum yield up to 69.1% for the solid polymer film and stable electrochemical cycling stability. The polyamide exhibited reversible color and emission switching even in hundreds of cycles, and the fluorescence on/off contrast ratio was determined up to 417, which is the highest value to our knowledge. Furthermore, as the response time is vital for the real-life applications, to speed up the response of electrofluorochromism, a porous polymer film was readily prepared through a facile method, notably exhibiting high fluorescence contrast, long-term stability and obviously improved response, due to the sharply increased surface area. Therefore, the AIE-functionalization combining the porous structure strategy will synergistically and dramatically improve the electrofluorochromic performance, which will also promote their practical applications in the near future.
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http://dx.doi.org/10.1021/acsami.8b01624DOI Listing
May 2018

Highly optical transparency and thermally stable polyimides containing pyridine and phenyl pendant.

Des Monomers Polym 2017 11;20(1):449-457. Epub 2017 Jul 11.

National & Local Joint Engineering Laboratory for Synthesis Technology of High Performance Polymer, Key Laboratory of High Performance Plastics, Ministry of Education, College of Chemistry, Jilin University, Changchun, P. R. China.

In order to obtain highly optical transparency polyimides, two novel aromatic diamine monomers containing pyridine and kinky structures, 1,1-bis[4-(5-amino-2-pyridinoxy)phenyl]diphenylmethane (BAPDBP) and 1,1-bis[4-(5-amino-2-pyridinoxy)phenyl]-1-phenylethane (BAPDAP), were designed and synthesized. Polyimides based on BAPDBP, BAPDAP, 2,2-bis[4-(5-amino-2-pyridinoxy)phenyl]propane (BAPDP) with various commercial dianhydrides were prepared for comparison and structure-property relationships study. The structures of the polyimides were characterized by Fourier transform infrared (FT-IR) spectrometer, wide-angle X-ray diffractograms (XRD) and elemental analysis. Film properties including solubility, optical transparency, water uptake, thermal and mechanical properties were also evaluated. The introduction of pyridine and kinky structure into the backbones that polyimides presented good optical properties with 91-97% transparent at 500 nm and a low cut-off wavelength at 353-398 nm. Moreover, phenyl pendant groups of the polyimides showed high glass transition temperatures ( ) in the range of 257-281 °C. These results suggest that the incorporating pyridine, kinky and bulky substituents to polymer backbone can improve the optical transparency effectively without sacrificing the thermal properties.
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http://dx.doi.org/10.1080/15685551.2017.1351766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784878PMC
July 2017

The invasive MED/Q Bemisia tabaci genome: a tale of gene loss and gene gain.

BMC Genomics 2018 01 22;19(1):68. Epub 2018 Jan 22.

Department of Entomology, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Science, No. 12 Zhongguancun Nandajie, Haidian District, Beijing, 100081, China.

Background: Sweetpotato whitefly, Bemisia tabaci MED/Q and MEAM1/B, are two economically important invasive species that cause considerable damages to agriculture crops through direct feeding and indirect vectoring of plant pathogens. Recently, a draft genome of B. tabaci MED/Q has been assembled. In this study, we focus on the genomic comparison between MED/Q and MEAM1/B, with a special interest in MED/Q's genomic signatures that may contribute to the highly invasive nature of this emerging insect pest.

Results: The genomes of both species share similarity in syntenic blocks, but have significant divergence in the gene coding sequence. Expansion of cytochrome P450 monooxygenases and UDP glycosyltransferases in MED/Q and MEAM1/B genome is functionally validated for mediating insecticide resistance in MED/Q using in vivo RNAi. The amino acid biosynthesis pathways in MED/Q genome are partitioned among the host and endosymbiont genomes in a manner distinct from other hemipterans. Evidence of horizontal gene transfer to the host genome may explain their obligate relationship. Putative loss-of-function in the immune deficiency-signaling pathway due to the gene loss is a shared ancestral trait among hemipteran insects.

Conclusions: The expansion of detoxification genes families, such as P450s, may contribute to the development of insecticide resistance traits and a broad host range in MED/Q and MEAM1/B, and facilitate species' invasions into intensively managed cropping systems. Numerical and compositional changes in multiple gene families (gene loss and gene gain) in the MED/Q genome sets a foundation for future hypothesis testing that will advance our understanding of adaptation, viral transmission, symbiosis, and plant-insect-pathogen tritrophic interactions.
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http://dx.doi.org/10.1186/s12864-018-4448-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778671PMC
January 2018

Astrocyte-Specific Deletion of Sox2 Promotes Functional Recovery After Traumatic Brain Injury.

Cereb Cortex 2019 01;29(1):54-69

Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX, USA.

Injury to the adult brain induces activation of local astrocytes, which serves as a compensatory response that modulates tissue damage and recovery. However, the mechanism governing astrocyte activation during brain injury remains largely unknown. Here we provide in vivo evidence that SOX2, a transcription factor critical for stem cells and brain development, is also required for injury-induced activation of adult cortical astrocytes. Genome-wide chromatin immunoprecipitation-seq analysis of mouse cortical tissues reveals that SOX2 binds to regulatory regions of genes associated with signaling pathways that control glial cell activation, such as Nr2e1, Mmd2, Wnt7a, and Akt2. Astrocyte-specific deletion of Sox2 in adult mice greatly diminishes glial response to controlled cortical impact injury and, most unexpectedly, dampens injury-induced cortical loss and benefits behavioral recovery of mice after injury. Together, these results uncover an essential role of SOX2 in somatic cells under pathological conditions and indicate that SOX2-dependent astrocyte activation could be targeted for functional recovery after traumatic brain injury.
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http://dx.doi.org/10.1093/cercor/bhx303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659023PMC
January 2019

Critical role of TRPC1 in thyroid hormone-dependent dopaminergic neuron development.

Biochim Biophys Acta Mol Cell Res 2017 Oct 2;1864(10):1900-1912. Epub 2017 Aug 2.

Department of Occupational Health, Third Military Medical University, No.30 Gaotanyan Street, Chongqing 400038, China. Electronic address:

Thyroid hormones play a crucial role in midbrain dopaminergic (DA) neuron development. However, the underlying molecular mechanisms remain largely unknown. In this study, we revealed that thyroid hormone treatment evokes significant calcium entry through canonical transient receptor potential (TRPC) channels in ventral midbrain neural stem cells and this calcium signaling is essential for thyroid hormone-dependent DA neuronal differentiation. We also found that TRPC1 is the dominant TRPC channel expressed in ventral midbrain neural stem cells which responds to thyroid hormone. In addition, thyroid hormone increases TRPC1 expression through its receptor alpha 1 during DA neuron differentiation, and, importantly, produces calcium signals by activating TRPC1 channels. In vivo and in vitro gene silencing experiments indicate that TRPC1-mediated calcium signaling is required for thyroid hormone-dependent DA neuronal differentiation. Finally, we confirmed that the activation of OTX2, a determinant of DA neuron development and the expression of which is induced by thyroid hormone, is dependent on TRPC1-mediated calcium signaling. These data revealed the molecular mechanisms of how thyroid hormone regulates DA neuron development from ventral midbrain neural stem cells, particularly endowing a novel physiological relevance to TRPC1 channels.
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http://dx.doi.org/10.1016/j.bbamcr.2017.07.019DOI Listing
October 2017

Identification of QTL and Qualitative Trait Loci for Agronomic Traits Using SNP Markers in the Adzuki Bean.

Front Plant Sci 2017 19;8:840. Epub 2017 May 19.

Key Laboratory of New Technology in Agricultural Application, College of Plant Science and Technology, Beijing University of AgricultureBeijing, China.

The adzuki bean () is an important grain legume. Fine mapping of quantitative trait loci (QTL) and qualitative trait genes plays an important role in gene cloning, molecular-marker-assisted selection (MAS), and trait improvement. However, the genetic control of agronomic traits in the adzuki bean remains poorly understood. Single-nucleotide polymorphisms (SNPs) are invaluable in the construction of high-density genetic maps. We mapped 26 agronomic QTLs and five qualitative trait genes related to pigmentation using 1,571 polymorphic SNP markers from the adzuki bean genome via restriction-site-associated DNA sequencing of 150 members of an F population derived from a cross between cultivated and wild adzuki beans. We mapped 11 QTLs for flowering time and pod maturity on chromosomes 4, 7, and 10. Six 100-seed weight (SD100WT) QTLs were detected. Two major flowering time QTLs were located on chromosome 4, firstly (PEVs 71.3%), co-segregating with SNP marker s690-144110, and (PEVs 67.6%) at a 0.974 cM genetic distance from the SNP marker s165-116310. Three QTLs for seed number per pod (, and ) were mapped on chromosomes 3 and 4. One QTL of seed thickness (SDT) and three QTLs for branch number on the main stem were detected on chromosome 4. QTLs for maximum leaf width (LFMW) and stem internode length were mapped to chromosomes 2 and 9, respectively. Trait genes controlling the color of the seed coat, pod, stem and flower were mapped to chromosomes 3 and 1. Three candidate genes, , and , were identified for flowering time and pod maturity. encodes an agamous-like MADS-box protein of 379 amino acids. encodes a phytochrome E protein of 1,121 amino acids. Four phytochrome genes (, and ) were identified in the adzuki bean genome. We found candidate genes and of SD100WT, of SDT, and of LFMW. A candidate gene related to black seed coat color was identified. These mapped QTL and qualitative trait genes provide information helpful for future adzuki bean candidate gene cloning and MAS breeding to improve cultivars with desirable growth periods, yields, and seed coat color types.
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http://dx.doi.org/10.3389/fpls.2017.00840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437206PMC
May 2017
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