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1.
Blood ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33197925

RESUMO

A number of clinically validated drugs have been developed by repurposing the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex with molecular glue degraders to eliminate disease-driving proteins. Here, we present the identification of a first-in-class GSPT1-selective cereblon E3 ligase modulator, CC-90009. Biochemical, structural and molecular characterization demonstrates that CC-90009 co-opts the CRL4CRBN to selectively target GSPT1 for ubiquitination and proteasomal degradation. Depletion of GSPT1 by CC-90009 rapidly induces AML apoptosis, reducing leukemia engraftment and leukemia stem cells (LSC) in large scale primary patient xenografting of 35 independent AML samples, including those with adverse risk features. Using a genome-wide CRISPR-Cas9 screen for effectors of CC-90009 response, we uncovered the ILF2 and ILF3 heterodimeric complex as a novel regulator of cereblon expression. Knockout of ILF2/ILF3 decreases the production of full-length cereblon protein via modulating CRBN mRNA alternative splicing, leading to diminished response to CC-90009. The screen also revealed that the mTOR signaling and the integrated stress response (ISR) specifically regulate the response to CC-90009 in contrast to other cereblon modulators. Hyperactivation of the mTOR pathway by inactivation of TSC1 and TSC2 protected against the growth inhibitory effect of CC-90009 by reducing CC-90009 induced binding of GSPT1 to cereblon and subsequent GSPT1 degradation. On the other hand, GSPT1 degradation promoted the activation of the GCN1/GCN2/ATF4 pathway and subsequent apoptosis in AML cells. Collectively, CC-90009 activity is mediated by multiple layers of signaling networks and pathways within AML blasts and LSC, whose elucidation gives insight into further assessment of CC-90009's clinical utility.

2.
Chemosphere ; : 128929, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33199111

RESUMO

The wide use and distribution of sulpiride (SP) has caused potential threats to the water environment and human health. In this study, ultrathin S-doped graphitic carbon nitride nanosheets (US-CN) was successfully synthesized and characterized, and its SP removal efficiency was evaluated under various conditions via the visible-light-assisted peroxydisulfate (PDS) activation method. The degradation pathways and mechanism were also discussed through quenching experiments, density functional theory (DFT) calculations, and intermediate products detection. After sulfur doping and ultrasonic treatment, graphitic carbon nitride (CN) possessed an ultra-thin and porous structure, which facilitated the electronic distribution and more photocurrent, thus resulting in the excellent stability and removal efficiency for SP via PDS activation upon visible light irradiation. The singlet oxygen (1O2) generated by the US-CN/PDS/VL system played a significant role in SP degradation. Based on the bonds of electron-rich atoms fracturing and the SO2 extrusion, the SP degradation pathway was proposed. This work provides a useful information for the SP photocatalytic degradation via PDS activation.

3.
ACS Chem Biol ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206504

RESUMO

There is a growing interest in using targeted protein degradation as a therapeutic modality in view of its potential to expand the druggable proteome. One avenue to using this modality is via molecular glue based Cereblon E3 Ligase Modulating Drug compounds. Here, we report the identification of the transcription factor ZBTB16 as a Cereblon neosubstrate. We also report two new Cereblon modulators, CC-3060 and CC-647, that promote ZBTB16 degradation. Unexpectedly, CC-3060 and CC-647 target ZBTB16 for degradation by primarily engaging distinct structural degrons on different zinc finger domains. The reciprocal fusion proteins, ZBTB16-RARα and RARα-ZBTB16, which cause a rare acute promyelocytic leukemia, contain these same structural degrons and can be targeted for proteasomal degradation with Cereblon modulator treatment. Thus, a targeted protein degradation approach via Cereblon modulators may represent a novel therapeutic strategy in acute promyelocytic leukemia where ZBTB16/RARA rearrangements are critical disease drivers.

4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(10): 1194-1198, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33198862

RESUMO

OBJECTIVE: To investigate the c-Jun N-terminal kinase (JNK), CCAAT/enhancer-binding protein homologous protein (CHOP) pathway apoptosis and the changes of cytokine levels in immune-related organs and tissues of sepsis mice at different time points. METHODS: Twenty-seven male BALB/c mice were divided into normal group, sepsis 6 hours group and sepsis 12 hours group by the block randomization method, with 9 mice in each group. The sepsis model was made by cecal ligation and puncture (CLP). Blood sample was collected from each group at the corresponding time point, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1ß, IL-10) were measured by enzyme linked immunosorbent assay (ELISA). The spleen, thymus and appendix tissues were taken from the mice to detect the expressions of phosphorylation-JNK (p-JNK), JNK1, CHOP and cleaved caspase-3 protein by Western Blot. RESULTS: The level of cytokines, p-JNK/JNK1 ratio, CHOP and caspase-3 in spleen tissues, and the CHOP, caspase-3 in thymus and appendix tissue in the sepsis 6 hours group were significantly higher than those in the normal group [serum TNF-α (ng/L): 24.29±3.09 vs. 2.93±2.09, serum IL-1ß (ng/L): 5.00±3.19 vs. 3.54±1.53, serum IL-10 (ng/L): 1 963.93±270.20 vs. 275.09±45.21, spleen p-JNK/JNK1 ratio: 0.257±0.126 vs. 0.154±0.068, spleen CHOP/ß-actin: 0.201±0.131 vs. 0.142±0.068, spleen caspase-3/ß-actin: 0.215±0.126 vs. 0.098±0.088, thymus CHOP/ß-actin: 0.122±0.071 vs. 0.089±0.067, thymus caspase-3/ß-actin: 0.258±0.145 vs. 0.108±0.045, appendix CHOP/ß-actin: 0.361±0.134 vs. 0.215±0.112, appendix caspase-3/ß-actin: 0.439±0.211 vs. 0.321±0.145, all P < 0.05]. However, there were no significant difference in the p-JNK/JNK1 ratio in thymus and appendix (thymus p-JNK/JNK1 ratio: 1.221±0.776 vs. 1.168±0.475, appendix p-JNK/JNK1 ratio: 2.014±1.227 vs. 1.828±0.915, both P > 0.05). Cytokine levels and the p-JNK/JNK1 ratio, CHOP, caspase-3 in spleen, thymus, and appendix in the sepsis 12 hours group were further increased when compared with those in the sepsis 6 hours group, except for a significant decrease in IL-10 level [serum IL-10 (ng/L): 1 698.98±210.52 vs. 1 963.93±270.20, serum TNF-α (ng/L): 41.66±6.57 vs. 24.29±3.09, serum IL-1ß (ng/L): 10.37±4.14 vs. 5.00±3.19, spleen p-JNK/JNK1 ratio: 0.399±0.135 vs. 0.257±0.126, spleen CHOP/ß-actin: 0.298±0.145 vs. 0.201±0.131, spleen caspase-3/ß-actin: 0.353±0.145 vs. 0.215±0.126, thymus p-JNK/JNK1 ratio: 1.667±0.891 vs. 1.221±0.776, thymus CHOP/ß-actin: 0.207±0.133 vs. 0.122±0.071, thymus caspase-3/ß-actin: 0.416±0.179 vs. 0.258±0.145, appendix p-JNK/JNK1 ratio: 2.425±1.361 vs. 2.014±1.227, appendix CHOP/ß-actin: 0.456±0.189 vs. 0.361±0.134, appendix caspase-3/ß-actin: 0.635±0.289 vs. 0.439±0.211, all P < 0.05]. CONCLUSIONS: The endoplasmic reticulum pathway JNK and CHOP pathways are involved in immune-related cell apoptosis and cytokine expression in mice with sepsis. Apoptosis is more obvious at 12 hours than at 6 hours, and the inflammatory response is stronger.


Assuntos
Sepse , Animais , Apoptose , Citocinas , MAP Quinase Quinase 4 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais , Fator de Necrose Tumoral alfa
5.
Environ Sci Technol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33186032

RESUMO

An "event-based" approach to characterize complex air pollutant mixtures was applied in the Oil Sands region of northern Alberta, Canada. This approach was developed to better-inform source characterization and attribution of the air pollution in the Indigenous community of Fort McKay, within the context of the lived experience of residents. Principal component analysis was used to identify the characteristics of primary pollutant mixtures, which were related to hydrocarbon emissions, fossil fuel combustion, dust, and oxidized and reduced sulfur compounds. Concentration distributions of indicator compounds were used to isolate sustained air pollution "events". Diesel-powered vehicles operating in the mines were found to be an important source during NOx events. Industry-specific volatile organic compound (VOC) profiles were used in a chemical mass balance model for source apportionment, which revealed that nearby oil sands operations contribute to 86% of the total mass of nine VOC species (2-methylpentane, hexane, heptane, octane, benzene, toluene, m,p-xylene, o-xylene, and ethylbenzene) during VOC events. Analyses of the frequency distribution of air pollution events indicate that Fort McKay is regularly impacted by multiple mixtures simultaneously, underscoring the limitations of an exceedance-based approach relying on a small number of air quality standards as the only tool to assess risk.

6.
Parasite ; 27: 65, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33231548

RESUMO

Enterocytozoon bieneusi is an intestinal pathogen that infects a wide range of species, including humans. Cattle constitute an important host for E. bieneusi; however, there is a scarcity of information on the prevalence and genotyping of E. bieneusi in cattle in the Hainan Province of China. In this study, PCR analysis of 314 fecal samples from cattle in six cities of Hainan was performed for genotype identification. The average prevalence of E. bieneusi in these animals was 9.9% (31/314), and ranged from 0.0% (0/12) to 20.5% (8/39). Five known genotypes - EbpC (n = 14), BEB4 (n = 12), J (n = 2), I (n = 1), and CHG5 (n = 1) - and a novel genotype: HNC-I (n = 1) - were identified. Genotypes EbpC and HNC-I were placed in zoonotic Group 1, and the remaining four genotypes (BEB4, J, I, and CHG5) were placed in Group 2. Since 93.5% of the genotypes found in the cattle (29/31) (EbpC, BEB4, J, and I) have previously been found in humans, these genotypes are probably involved in the transmission of microsporidiosis to humans.

7.
Viral Immunol ; 33(9): 573-584, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33030418

RESUMO

Virus replication and host cell growth require host cell metabolic networks to provide energy and precursors for the synthesis of macromolecules. The aim of this study was to investigate the most direct changes in energy metabolism and small-molecule metabolism of Madin-Darby canine kidney (MDCK) cells infected with H3N2 canine influenza virus (CIV) and to determine whether small metabolites contribute to the pathogenesis of CIV. To study the metabolomics of MDCK cells infected with H3N2 CIV, we used liquid chromatography-tandem mass spectrometry combined with multivariate statistical analysis. The results showed that 798 positive ions were detected, among which 33 were upregulated and 11 were downregulated, and 406 negative ions were detected, among which 33 were upregulated and 9 were downregulated. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we found that these differentially expressed molecules were mainly concentrated in the steroid hormone biosynthesis, amino sugar and nucleotide sugar metabolism, sphingolipid metabolism, vitamin B6 metabolism, cysteine and methionine metabolism, vitamin digestion and absorption, arginine and proline metabolism, biosynthesis of amino acids, and folate biosynthesis metabolic pathways. These pathways are involved in energy metabolism and nucleic acid and protein synthesis, which are essential for virus replication. Our experimental data suggest that H3N2 CIV infection reconstitutes/influences cellular metabolic processes, which in turn may contribute to viral replication. These findings are important for the development of enzyme inhibitors or metabolites for the identification of antiviral drugs. In addition, understanding the metabolic interaction between CIV and host cells is also very important for the complex pathogenicity of CIV, providing certain guidance for the treatment of canine influenza.

8.
Life Sci ; 262: 118543, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038381

RESUMO

AIMS: Premature ovarian failure (POF) is a phenomenon in which the ovaries fail before the age of 40 years. Prior research has used a wide range of mouse models designed to reflect different causes of POF, including genetic factors, iatrogenic factors, and immune factors. The current study employed a mouse model of POF induced by 4-vinylcyclohexene diepoxide (VCD). VCD can specifically kill primordial and primary ovarian follicles, which destroys the follicular reserve and causes POF. The current study sought to specify and extend the applications of this model by examining the effect of timing and VCD dose and by exploring the effect of the model on systems outside of the ovaries. MATERIALS AND METHODS: A VCD-induced mouse model of POF was constructed using established methods (VCD injected continuously at a concentration of 160 mg/kg for 15 days). Evidence for a graded effect of VCD was observed using a range of concentrations, and the best windows for examining VCD's effects on follicles and associated tissues were identified. KEY FINDINGS: The mouse model used here successfully simulated two common complications of POF - emotional changes and decreased bone density. The model's application was then extended to examine the links between disease and intestinal microorganisms, and evidence was found linking POF to the reproductively relevant composition of the gut microbiota. SIGNIFICANCE: These findings provide novel methodological guidance for future research, and they significantly extend the applications and scope of VCD-induced POF mouse models.

9.
Sci Adv ; 6(42)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33067234

RESUMO

Moiré superlattices in van der Waals (vdW) heterostructures could trap long-lived interlayer excitons. These moiré excitons could form ordered quantum dot arrays, paving the way for unprecedented optoelectronic and quantum information applications. Here, we perform first-principles simulations to shed light on moiré excitons in twisted MoS2/WS2 heterostructures. We provide direct evidence of localized interlayer moiré excitons in vdW heterostructures. The interlayer and intralayer moiré potentials are mapped out based on spatial modulations of energy gaps. Nearly flat valence bands are observed in the heterostructures. The dependence of spatial localization and binding energy of the moiré excitons on the twist angle of the heterostructures is examined. We explore how vertical electric field can be tuned to control the position, polarity, emission energy, and hybridization strength of the moiré excitons. We predict that alternating electric fields could modulate the dipole moments of hybridized moiré excitons and suppress their diffusion in moiré lattices.

10.
Transbound Emerg Dis ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33119963

RESUMO

Lumpy skin disease (LSD) is a viral disease of cattle caused by LSD virus (LSDV). This disease poses a significant threat to stockbreeding and is listed as one of bovine notifiable diseases by OIE. Before 2019, LSD has not been reported in China. The first LSD outbreak was determined in China on August 3, 2019. Since then, a total of 7 LSD outbreaks have been reported in other 6 provinces in China, infecting 91 and killing 7 cattle. As of now, LSDV was detected in western and eastern China and also in Taiwan Island outside Mainland China. LSD is undoubtedly an emerging threat to the cattle industry in China.

11.
Parasit Vectors ; 13(1): 438, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878633

RESUMO

BACKGROUND: Rodents, globally overpopulated, are an important source for zoonotic disease transmission to humans, including Enterocytozoon bieneusi (one of the most prevalent zoonotic pathogens). Here, we studied the prevalence and performed genetic analyses of E. bieneusi in rodents from the Hainan Province of China. METHODS: A total of 603 fresh fecal samples were gathered from 369 wild rats, 117 bamboo rats, 93 Asiatic brush-tailed porcupine and 24 red-bellied squirrels. The wild rats were identified to the species level by amplification of a 421-bp region of the cytb gene from fecal DNA using PCR. Genotype analysis was performed by amplification of the internal transcribed spacer (ITS) region of rDNA of E. bieneusi using PCR. RESULTS: Seven wild rat species were identified. The average rate of infection with E. bieneusi was 15.8% (95/603) with 18.7% (69/369) in wild rats, 11.9% (25/210) in farmed rodents and 4.2% (1/24) in red-bellied squirrels. Sixteen E. bieneusi genotypes were identified, including 9 known genotypes (D, Type IV, PigEBITS7, Peru8, Peru11, ESH02, S7, EbpA and CHG5), and 7 novel genotypes (HNR-I to HNR-VII). Genotype D (44.2%, 42/95) predominated, followed by PigEBITS7 (20.0%, 19/95), HNR-VII (15.8%, 15/95), Type IV (5.3%, 5/95), HNR-III (2.1%, 2/95), HNR-VI (2.1%, 2/95) and each of the remaining 10 genotypes (1.1%, 1/95). The phylogenetic analysis of the ITS region of E. bieneusi divided the identified genotypes into the following four groups: Group 1 (n = 13), Group 2 (n = 1), Group 12 (n = 1), and the novel Group 13 (n = 1). CONCLUSIONS: To our knowledge, this is the first report on the identification of E. bieneusi in rodents from Hainan, China. The zoonotic potential of the identified E. bieneusi genotypes suggested that the rodents poses a serious threat to the local inhabitants. Thus, measures need to be taken to control the population of wild rats in the areas investigated in this study, along with identification of safe methods for disposal of farmed rodent feces. Additionally, the local people should be made aware of the risk of disease transmission from rodents to humans.

12.
Int J Mol Sci ; 21(18)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927746

RESUMO

Anthracnose caused by Colletotrichum acutatum is one of the most devastating fungal diseases of pepper (Capsicum annuum L.). The utilization of chitin-binding proteins or chitinase genes is the best option to control this disease. A chitin-binding domain (CBD) has been shown to be crucial for the innate immunity of plants and activates the hypersensitive response (HR). The CaChiIII7 chitinase gene has been identified and isolated from pepper plants. CaChiIII7 has repeated CBDs that encode a chitinase enzyme that is transcriptionally stimulated by C. acutatum infection. The knockdown of CaChiIII7 in pepper plants confers increased hypersensitivity to C. acutatum, resulting in its proliferation in infected leaves and an attenuation of the defense response genes CaPR1, CaPR5, and SAR8.2 in the CaChiIII7-silenced pepper plants. Additionally, H2O2 accumulation, conductivity, proline biosynthesis, and root activity were distinctly reduced in CaChiIII7-silenced plants. Subcellular localization analyses indicated that the CaChiIII7 protein is located in the plasma membrane and cytoplasm of plant cells. The transient expression of CaChiIII7 increases the basal resistance to C. acutatum by significantly expressing several defense response genes and the HR in pepper leaves, accompanied by an induction of H2O2 biosynthesis. These findings demonstrate that CaChiIII7 plays a prominent role in plant defense in response to pathogen infection.

13.
Materials (Basel) ; 13(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977515

RESUMO

The effect of ultrasonic temperature on density, microstructure and mechanical properties of vacuum counter-pressure casting ZL114A alloy during solidification was investigated by optical microscopy (OM), scanning electron microscope (SEM) and a tensile test. The results show that compared with the traditional vacuum counter-pressure casting aluminum alloy, the primary phase and eutectic silicon of the alloy with ultrasonic treatment has been greatly refined due to the dendrites broken by ultrasonic vibration. However, the refining effect of ultrasonic treatment on vacuum counter-pressure casting aluminum alloy will be significantly affected by ultrasonic temperature. When the ultrasonic temperature increases from 680 °C to 720 °C, the primary phase is gradually refined, and the morphology of eutectic silicon also changes from coarse needle-like flakes to fine short rods. With a further increase in the ultrasonic temperature, the microstructure will coarse again. The tensile strength and elongation of vacuum counter-pressure casting ZL114A alloy increases first and then decreases with the increase of ultrasonic temperature. The optimal mechanical properties were achieved with tensile strength of 327 MPa and the elongation of 5.57% at ultrasonic temperature of 720 °C, which is 6.3% and 8.2%, respectively, higher than that of alloy without ultrasonic treatment.

14.
Materials (Basel) ; 13(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977612

RESUMO

In this paper, in order to improve the performance of the ZL205A castings, continuous ultrasonic and pulsed ultrasonic treatments were applied to the melted alloy to study the effect of ultrasound propagation distance on microstructure and microhardness. The results indicated that ZL205A grains were significantly refined by ultrasonic vibration, but the refinement effect became weak gradually with the increase of sampling depth. The minimum grain sizes were 103.2 µm and 122.5 µm respectively in continuous and pulsed ultrasonic treatment. Grain boundary segregation also became more serious and coarser with the increase of vertical depth. In addition, microhardness and vertical depth are not positively correlated linearly. As the vertical depth increased, microhardness first decreased and then increased, the maximum hardnesses were 73.9 HV and 72.84 HV, respectively, in the two process modes. According to the experiment results and available studies, the mechanism of ultrasonic treatment maybe that: the cooling rate of solidification interface front increased by cavitation and streaming, thus changing the solute redistribution behavior of the ZL205A melt.

15.
J Am Chem Soc ; 142(41): 17469-17479, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32927954

RESUMO

The singlet fission (SF) channels in many systems are controlled by the thermodynamic driving force (Switch-1) and kinetic barrier (Switch-2), both of which could be modulated by chromophore structure dynamics and solvent properties. Using ab initio molecular dynamics (AIMD), we here simulate how the structural dynamics and solvent jointly govern singlet prefission energetics, taking a covalent BODIPY dimer (di-BODIPY) in solvents as an example. We report a general dual-switched dynamic channel for intramolecular SF in solvents and suggest an effective AIMD sampling method to characterize the joint effect of chromophore structure dynamics and the solvent impact on SFs. Results reveal that the joint effect not only provides di-BODIPY more chances for meeting the SF thermodynamic requirement (Switch-1 ON) but also tunes the charge-transfer state toward removing the kinetic barrier (Switch-2 ON). Two factors jointly govern each switch in the dual-switched SF channel, and any one does not open the channel alone. We suggest a general principle for dynamically dual-switching the SF channel in solvents by utilizing the joint effect to tune the pre-SF energetics for photoexcitation and the opening of the subsequent channel. AIMD sampling is used for the first time to discover explicit solvent-solute interaction and dynamics information and thus their effect on excitation energetics. This work also shows the statistical information for an ensemble of SF chromophores in solvents, which can undergo different photoexcitations and possible SFs. The high agreement of the findings here with the experiments justifies our AIMD sampling-based pre-SF energetic prediction as a reliable way for exploring novel SF systems and their controllability.

16.
J Phys Chem Lett ; : 6982-6989, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787199

RESUMO

In two-dimensional (2D) halide perovskites, four distinct types of intramolecular band alignment (Ia, Ib, IIa, and IIb) can be formed between the organic and inorganic components. Molecular design to achieve desirable band alignments is of crucial importance to the applications of 2D perovskites and their heterostructures. In this work, by means of first-principles calculations, we have developed molecular design strategies that lead to the discovery of 2D halide perovskites with favorable band alignments toward light-emitting and photovoltaic applications. The same design strategies can be extended to vertical and lateral heterostructures of 2D perovskites with selective light emissions from the organic and/or inorganic layer of constituent 2D perovskites. For each intramolecular band alignment, the charge density and binding energy of the lowest energy exciton are examined. The effect of spin-orbit coupling (SOC) on the band structures is assessed. While SOC significantly lowers the band gaps in type-Ia and type-IIa alignments, it has a negligible effect in type-Ib and type-IIb alignments.

17.
Arch Virol ; 165(11): 2699-2702, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32851431

RESUMO

Canine bufavirus (CBuV) is a novel protoparvovirus of dogs that was first reported in 2018 in Italy. The prevalence and genetic diversity of CBuV in China are not clear. In this study, a total of 115 canine fecal samples were collected from northern China in 2019, and two of the samples tested positive for CBuV DNA by PCR. These two field CBuV strains were designated Henan38 and Henan44. The complete genomic sequences of Henan38 and Henan44 were obtained by gap-filling PCR, sequenced, and assembled. Phylogenetic analysis demonstrated that the two strains clustered together in a novel group that was distant from previously reported CBuV strains. This study will strengthen our understanding of the epidemiology and genetic diversity of CBuV in China.


Assuntos
Evolução Molecular , Variação Genética , Infecções por Parvoviridae/veterinária , Parvovirus Canino/classificação , Filogenia , Animais , Sequência de Bases , China , Doenças do Cão/virologia , Cães , Fezes/virologia , Genoma Viral , Parvovirus Canino/isolamento & purificação
18.
J Phys Chem Lett ; : 7650-7656, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32820939

RESUMO

A surface plasmon can drive many photochemical reactions, in which effective charge separation and migration is a key. In analogy to the plasmon-semiconductor interface, the plasmon-molecule interface may also be used to improve the separation and migration of hot carriers. In this work, by using in situ Raman spectroscopy, molecular grafting on silver nanostructures is found essential for modulating the charge separation and p-aminothiophenol (PATP) oxidation reaction. When the LUMO of the grafted molecules match well the energy distribution of the plasmon-generated hot electrons, the PATP oxidation process accelerates significantly. Moreover, compared with symmetrical grafting, asymmetrical grafting is more effective in regulating the charge separation and plasmon-mediated chemical reaction. This work provides an effective strategy for deep understanding and fine modulation of plasmon-mediated photochemistry.

19.
Insect Sci ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32757245

RESUMO

The whitefly Bemisia tabaci is a notorious agricultural pest of many crops worldwide. Although it is thought that B. tabaci secretes saliva into the host plant to counter plant defenses, knowledge on the whitefly salivary proteome is limited. Here, we characterized the gene/protein repertoires of B. tabaci salivary glands and secreted saliva by transcriptomic and liquid chromatography tandem mass spectroscopy analyses. A total of 698 salivary gland-enriched unigenes and 171 salivary proteins were identified. Comparative analysis between the B. tabaci salivary proteins and those of different arthropod species revealed numerous similarities in proteins associated with binding, hydrolysis, and oxidation-reduction, which demonstrates a degree of conservation across herbivorous saliva. There were 74 proteins only identified in B. tabaci saliva, of which 34 were B. tabaci-specific. In addition, 13 salivary proteins, of which 11 were B. tabaci-specific, were differentially regulated when B. tabaci fed on different hosts. Our results provide a good resource for future functional studies of whitefly salivary effectors, and might be useful in pest management.

20.
Environ Sci Technol ; 54(18): 11464-11475, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32841022

RESUMO

Mounting evidence shows that organophosphate flame retardants (OPFRs), especially aryl- and halogenated-OPFRs, exert various adverse health effects on living organisms. This study evaluated the hepatotoxic effect of trihexyl phosphate (THP) as a long-chain alkyl-OPFR on human hepatocyte cells (LO2) and mouse hepatocyte cells (AML12) by performing screening of cytotoxicity in vitro. In combination with transcriptomic analysis, toxicological mechanisms in vitro were further investigated. Results showed that THP triggered hepatotoxicity in vitro by altering four signaling pathways: endoplasmic reticulum (ER) stress, apoptosis, cell cycle, and the glycolysis signaling pathway. Exposure of LO2 and AML12 liver cells to THP (25 µg/mL) significantly induced ER stress-mediated apoptosis and cell cycle arrest. Meanwhile, downregulation of glycolysis caused the blockage of energy metabolism. Furthermore, the high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) revealed that much of THP was absorbed into the cells and displayed stability in the two liver cell lines. In vivo assays using a mouse model demonstrated that exposure to THP at 400 mg/kg induced the ballooning degeneration of hepatocytes in liver tissue, whereas exposure to THP at 800 mg/kg caused acute liver injury with high alanine aminotransferase levels. This study provides novel insights into the impact of THP on hepatotoxicity in vitro and in vivo and uncovers the underlying toxicological mechanisms, which may serve as a guide for further ecological risk assessment and reasonable application of alkyl-OPFRs.

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