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1.
Artigo em Inglês | MEDLINE | ID: mdl-33442859

RESUMO

Recently, the same fish diseases, which have been found in pond farming, have been found in the newly tested largemouth bass (Micropterus salmoides) system. Bacterial septicemia caused by Aeromonas hydrophila occurs frequently in largemouth bass culture leading to significant economic losses. To investigate the role miRNA in the largemouth bass disease resistance, twelve (2 tissues (spleen and head kidney) × 2 experimental groups (infected and control) × three biological replicates) small RNA libraries were constructed and sequenced with miRNA-seq. A total of 26 differentially expressed miRNAs, 8 upregulated and 18 downregulated, were identified in the spleen, and 19 differentially expressed miRNAs, 9 upregulated and 10 downregulated, were identified in head kidney (fold change ≥ 2 or ≤ 0.5 and P ≤ 0.05). The differentially expressed miRNAs with the largest fold change were selected for target gene prediction using GO and KEGG analysis. Six miRNAs in the spleen and 5 miRNAs in the head kidney were selected. Analysis showed that, of all the immune and metabolic pathways, the FoxO signaling pathway was enriched in both the spleen and head kidney groups. Common target genes of the pathway included AMP-activated catalytic subunit alpha 1 (prkaa1), phosphatidylinositol 3-kinase (pik3r3b), serine/threonine-protein kinase (plk2), and forkhead box protein G1 (foxg1a). MiRNAs (such as miR-126-5P, miR-126-3P) are involved in immune response and cell cycle functions as they regulate targeted genes in the FoxO pathway. These results will enhance our understanding of the molecular mechanisms underlying immune responses to bacterial septicemia and facilitate molecular-assisted selection of resistant strains of largemouth bass.

2.
Ecotoxicol Environ Saf ; 208: 111654, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396168

RESUMO

Salicylic acid (SA) is an important signal molecule, regulating oxidative stress response in plants. In this study, we evaluated the influences of SA (1 mg L-1, 10 mg L-1 and 50 mg L-1) on the accumulation of clothianidin (CLO), dinotefuran (DFN) and difenoconazole (DFZ) (5 mg L-1) and pesticide-induced (CLO-10 mg L-1, DFN-20 mg L-1, and DFZ-10 mg L-1) oxidative stress in cucumber plants. Exogenous SA at 10 mg L-1 significantly reduced the half-lives of three pesticides in nutrient solution and prevented the accumulation of pesticides in roots and leaves. And the role of SA in reducing residues was related to the major accumulation sites of pesticides. By calculating the root concentration factor (RCF) and translocation factor (TF), we found that SA at 10 mg L-1 reduced the ability of roots to absorb pesticides and enhanced the translocation ability from roots to leaves. Roots exposed to high concentrations of three pesticides could reduce biomass, low chlorophyll content, increase the accumulation of reactive oxygen species (ROS) and proline, promote lipid peroxidation, and alter the activities of a range of antioxidant enzymes, respectively. Exogenous SA at low concentrations (1 mg L-1 and 10 mg L-1) significantly mitigated these negative effects. Hence, application of exogenous SA at 10 mg L-1 could effectively alleviate the accumulation of pesticides and induce stress tolerance in cucumber planting systems.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33410070

RESUMO

Cd, Cr, Cu, Pb, and Zn concentrations were measured in oysters (C. gigas), plankton, and seawater during spring, summer, and autumn in Liaodong Bay (Bohai Sea, China) to elucidate the effects of season, region, and oyster size on metal bioaccumulation in oysters. Metal concentrations were quantified via atomic absorption spectrophotometry. Our study determined that metal concentrations in oysters, plankton, and seawater were the highest in summer, whereas the lowest levels occurred in autumn. Regarding oyster sizes, the highest Pb levels occurred in C3-sized oysters (> 5-cm length), whereas the highest Cd, Cr, Cu, and Zn levels occurred in C2 (3-5-cm length) oysters. In contrast, the lowest Cu and Pb levels occurred in C1 (< 3-cm length) oysters, whereas the lowest mean Cd, Cr, and Zn concentrations were observed in C3 oysters. Significant differences in trace metal concentrations in the three sample types were observed in all sampling sites.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33400109

RESUMO

Pyraclostrobin (PYR), a fungicide of the strobilurin class, is used to control many different kinds of fungal diseases in greenhouses and on agricultural fields. In the present study, an efficient method was established for simultaneously determining PYR and its metabolite BF 500-3 in cucumber fruits, leaves, and soil matrices using QuEChERS pretreatment coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The residue levels and dissipation kinetics of PYR were determined under greenhouse conditions. The recoveries ranged from 89.8 to 103.6% with relative standard deviations (RSDs) of 3.6-7.5% at three spiking levels. The results demonstrated that PYR dissipated quickly in the cucumber field with half-lives (DT50) of 2.14-4.17 days on different sites and in different matrices. The residue of its metabolite BF 500-3 was very low and showed a trend of first increasing and then decreasing. The degradation rate of PYR in soil was the fastest, followed by that on cucumber fruits and leaves. The terminal residue of PYR at an application rate of 150 g a.i. ha-1 (the maximum recommended rate) in cucumber fruits was below the maximum residue limit (MRL) of 0.5 mg/kg established in China. However, the application of the fungicide at 225 g a.i. ha-1 (1.5× the maximum recommended rate) resulted in residues that were above the MRL 1 day after the final application, which is an unacceptable risk. Therefore, the application dosage of PYR at the recommended rates was safe to human beings and animals.

5.
Hum Cell ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33387362

RESUMO

Hepatocellular Carcinoma (HCC) is the second leading cause of cancer-related deaths. Neuroblastoma associated transcript 1 (NBAT1) is a newly identified long noncoding RNA (lncRNA), which has been reported to play an important role in human cancers. However, the functional role and underlying mechanism of NBAT1 in HCC remains unclear. Here, we found that the expression of NBAT1 was decreased in HCC tissues and cells; as well, the decreased expression of NBAT1 was also associated with tumor size and clinical TNM stages. NBAT1 overexpression, both in vitro and in vivo studies, inhibited tumorigenesis through apoptosis augmentation and cell cycle blockade. Mechanistically, NBAT1 bound to IGF2BP1 and inhibited the interaction between IGF2BP1 and c-Myc mRNA, thus suppressing the stability of c-Myc mRNA. Collectively, NBAT1 is associated with HCC tumorigenesis and could be a therapeutic target for HCC treatment.

6.
Int J Nanomedicine ; 16: 239-248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33469284

RESUMO

Background: Radiotherapy occupies an essential position as one of the most significant approaches for the clinical treatment of cancer. However, we cannot overcome the shortcoming of X-rays which is the high value of the oxygen enhancement ratio (OER). Radiosensitizers with the ability to enhance the radiosensitivity of tumor cells provide an alternative to changing X-rays to protons and heavy ion radiotherapy. Materials and Methods: We prepared the Au-Pt nanoparticles (Au-Pt NPs) using a one-step method. The characteristics of the Au-Pt NPs were determined using TEM, HAADF-STEM, elemental mapping images, and DLS. The enhanced radiotherapy was demonstrated in vitro using MTT assays, colony formation assays, fluorescence imaging, and flow cytometric analyses of the apoptosis. The biodistribution of the Au-Pt NPs was analyzed using ICP-OES, and thermal images. The enhanced radiotherapy was demonstrated in vitro using immunofluorescence images, tumor volume and weigh, and hematoxylin & eosin (H&E) staining. Results: Polyethylene glycol (PEG) functionalized nanoparticles composed of the metallic elements Au and Pt were designed to increase synergistic radiosensitivity. The mechanism demonstrated that heavy metal NPs possess a high X-ray photon capture cross-section and Compton scattering effect which increased DNA damage. Furthermore, the Au-Pt NPs exhibited enzyme-mimicking activities by catalyzing the decomposition of endogenous H2O2 to O2 in the solid tumor microenvironment (TME). Conclusion: Our work provides a systematically administered radiosensitizer that can selectively reside in a tumor via the EPR effect and enhances the efficiency of treating cancer with radiotherapy.

7.
J Surg Res ; 257: 267-277, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32862055

RESUMO

BACKGROUND: MicroRNAs have been reported to play regulatory functions in various cancers, including esophageal cancer. The aim of this study was to investigate the effects of miR-140 on the progression of esophageal cancer and the underlying regulatory mechanism. METHODS: The levels of miR-140 and zinc finger E-box-binding homeobox 2 (ZEB2) messenger RNA in esophageal cancer tissues and cell lines were measured by quantitative real-time polymerase chain reaction. The protein levels of ZEB2, ß-catenin, c-Myc, and cyclinD1 were determined by Western blot. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. Cell migration and invasion were assessed by transwell assay. In addition, the relationship between miR-140 and ZEB2 was predicted by TargetScan online database and confirmed by dual-luciferase reporter assay. The tumor xenograft model was used to verify the role of miR-140 in esophageal cancer progression in vivo. RESULTS: The expression of miR-140 was downregulated whereas ZEB2 expression was upregulated in esophageal cancer tissues compared with paracancerous normal tissues. Functionally, both miR-140 overexpression and ZEB2 knockdown inhibited proliferation, migration, and invasion and induced apoptosis in esophageal cancer cells. ZEB2 overexpression reversed the effects of miR-140 on proliferation, apoptosis, migration, and invasion of esophageal cancer cells. Mechanistically, ZEB2 was identified as a target of miR-140. Furthermore, miR-140 suppressed Wnt/ß-catenin pathway by regulating ZEB2 expression in esophageal cancer cells. MiR-140 inhibited tumor growth of esophageal cancer through repressing ZEB2 expression in vivo. CONCLUSIONS: Our results demonstrated that miR-140 inhibited esophageal cancer development by targeting ZEB2 through inactivating Wnt/ß-catenin pathway.


Assuntos
Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Via de Sinalização Wnt/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Esôfago/patologia , Esôfago/cirurgia , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Estudos Retrospectivos , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
8.
Life Sci ; 265: 118739, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33186567

RESUMO

AIMS: The therapeutic effects of spermidine on preexisting obese mice have been not fully elucidated. In this study, we assessed the anti-obesity impact of spermidine on high-fat diet (HFD)-induced obese mice. MAIN METHODS: C57BL/6J mice were fed a HFD for 16 weeks to induce obesity, and then treated with or without spermidine via drinking water for additional 8 weeks. The contributions of spermidine in regulating obesity phenotypes and metabolic syndrome were further evaluated. KEY FINDINGS: Spermidine administration lowered fat mass and plasma lipid profile in HFD-induced obese mice without affecting body weight. In addition, spermidine attenuated hepatic steatosis by regulating lipid metabolism and enhancing antioxidant capacity. Moreover, spermidine reduced adipose tissue inflammation by decreasing inflammatory cytokine and chemokines expression, and these results might contributed to the enhanced thermogenic gene expression in brown adipose tissue. Furthermore, spermidine treatment enhanced gut barrier function by up-regulating tight junction- and mucin-related gene expression. SIGNIFICANCE: Spermidine-mediated protective impacts involve the regulation of lipid metabolism, inflammation response, gut barrier function and thermogenesis. These findings demonstrate that spermidine has potentials in treating obesity.

9.
Glob Chang Biol ; 27(2): 215-217, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33098149

RESUMO

To limit global temperature rise, scientists have proposed significant potentials for climate change mitigation from protecting and managing natural systems. However, depending on the time taken for technology deployment and natural carbon gain, actual mitigation can be dramatically delayed, and total mitigation by 2030 or 2050 can be more than halved compared to the estimated potential. Delayed or lack of action on implementation would push back the timeline to reduce greenhouse gas emissions, largely undermining the Paris goals. Launching actions now and learning from past experience can help deliver climate mitigation and sustainable development goals.

10.
Front Genet ; 11: 563947, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281869

RESUMO

Doublesex and mab-3-related transcription factor (dmrt) genes are widely distributed across various biological groups and play critical roles in sex determination and neural development. Here, we applied bioinformatics methods to exam cross-species changes in the dmrt family members and evolutionary relationships of the dmrt genes based on genomes of 17 fish species. All the examined fish species have dmrt1-5 while only five species contained dmrt6. Most fish harbored two dmrt2 paralogs (dmrt2a and dmrt2b), with dmrt2b being unique to fish. In the phylogenetic tree, 147 DMRT are categorized into eight groups (DMRT1-DMRT8) and then clustered in three main groups. Selective evolutionary pressure analysis indicated purifying selections on dmrt1-3 genes and the dmrt1-3-2(2a) gene cluster. Similar genomic conservation patterns of the dmrt1-dmrt3-dmrt2(2a) gene cluster with 20-kb upstream/downstream regions in fish with various sex-determination systems were observed except for three regions with remarkable diversity. Synteny analysis revealed that dmrt1, dmrt2a, dmrt2b, and dmrt3-5 were relatively conserved in fish during the evolutionary process. While dmrt6 was lost in most species during evolution. The high conservation of the dmrt1-dmrt3-dmrt2(2a) gene cluster in various fish genomes suggests their crucial biological functions while various dmrt family members and sequences across fish species suggest different biological roles during evolution. This study provides a molecular basis for fish dmrt functional analysis and may serve as a reference for in-depth phylogenomics.

11.
Chin Med ; 15(1): 118, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33292331

RESUMO

BACKGROUND: Cancer cells through autophagy-mediated recycling to meet the metabolic demands of growth and proliferation. The steroidal saponin 20(S)-ginsenoside Rh2 effectively inhibits the growth and survival of a variety of tumor cell lines and animal models, but the effects of Rh2 on autophagy remain elusive. METHODS: Cell viability was measured by CCK-8 (cell counting kit-8) assays. Apoptosis, ROS generation and mitochondrial membrane potential were analyzed by flow cytometry. Western blot analyses were used to determine changes in protein levels. Morphology of apoptotic cells and autophagosome accumulation were analyzed by DAPI staining and transmission electron microscopy. Autophagy induction was monitored by acidic vesicular organelle staining, EGFP-LC3 and mRFP-GFP-LC3 transfection. Atg7 siRNA and autophagy regulator was used to assess the effect of autophagy on apoptosis induced by G-Rh2. RESULTS: In this study, we found that low concentration G-Rh2 attenuated cancer cell growth and induced apoptosis upon serum-free starvation. Caspase 3 inhibitors failed to block apoptosis in G-Rh2-treated cells, indicating a caspase-independent mechanism. G-Rh2-treated cells in serum-deprived conditions showed impaired mitochondrial function, increased release and nuclear translocation of apoptosis-inducing factor, but little changes in the mitochondrial and cytoplasmic distributions of cytochrome C. Annexin A2 overexpression in 293T cells inhibited G-Rh2-induced apoptosis under serum-starved conditions. Meanwhile, G-Rh2 reduced lysosomal activity and inhibited the fusion of autophagosome and lysosome, leading to a block of autophagic flux. Knockdown Atg7 significantly inhibited autophagy and triggered AIF-induced apoptosis in serm free condition. The autophagy inducer significantly decreased the apoptosis levels of G-Rh2-treated cells in serum-free conditions. CONCLUSIONS: Under nutrient deficient conditions, G-Rh2 represses autophagy in cervical cancer cells and enhanced apoptosis through an apoptosis-inducing factor mediated pathway.

12.
Clin Neurol Neurosurg ; 201: 106401, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33340838

RESUMO

OBJECTIVES: To study the ability of Micropure® ultrasound technique to identify microcalcifications in carotid plaques. METHODS: Forty-four carotids in 22 patients were enrolled in this study and were detected by routine ultrasound examination and Micropure® examination at the same time to identify microcalcifications in plaques. The results were compared with the tissue-background ratio (TBR) in 18F-NaF PET-CT imaging, which was performed one or two days after the ultrasound examination. RESULTS: In the 44 carotids, plaques were detected in 37 carotids. Microcalcifications were detected by the Micropure® technique in 32 carotids, which were located surrounded by macrocalcifications in 23 carotids, in the fibre cap in 12 carotids, and in the base of the plaque in 6 carotids. Microcalcifications were not detected in 12 carotids. In 18F-NaF PET-CT examination, TBR > 1.61 (range 1.62-3.99, mean 2.25 ± 0.58) was detected in 37 carotids, and TBR < 1.61 was detected in 7 carotids. There were no significant differences between the two methods in detecting microcalcifications (p = 0.180). The sensitivity of the Micropure® technique in detecting microcalcifications was 81.08 %, and the specificity was 71.43 %. CONCLUSIONS: Microcalcifications in the carotid artery detected by the Micropure® technique were well in accordance with 18F-NaF PET-CT scanning, with better sensitivity and specificity.

13.
Cell Mol Biol (Noisy-le-grand) ; 66(7): 24-30, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33287918

RESUMO

Oral tumors are malignant cancers caused by abnormal proliferation or pathological changes of soft or hard tissues in the oral cavity. Serious cases may pose a threat to life. However, its precancerous lesions remain unclear. This study is based on a comprehensive strategy to explore a multi-factor-driven oral cancer barrier module, which is an attempt to describe the pathogenesis of the disease and potential regulatory drugs from a global perspective. Functional disease modules were identified by constructing a protein-specific interaction network in patients' oral tissues. Then, comprehensive pathogenesis was explored through combination with analysis of functional and signaling pathway enrichment, prediction of key regulatory factors. It was found that these specifically expressed proteins and their interactions often play a pivotal part in oral tumors. This is reflected in the results of functional and pathway enrichment of modulating genes, which show that they are mainly involved in various immune responses, inflammatory reactions, oral plaque, and oral ulcer-related regulatory processes. This may represent the potential pathogenesis of oral tumors. On the predictive analysis of regulators, a series of ncRNAs (including miR-590, CRNDE and miR-340) and transcription factors (including E2F1, MYC and TP53) were identified that have potential important regulatory effects on oral tumors. These key regulators may manipulate a crucial part of the module sub-network and then work together to mediate the occurrence of oral tumors. On the comprehensive Multi-omics module analysis, the specific proteins and their interactions in patients' oral tissues were identified, while the prominent pivotal regulators were involved in the different pathogenic functions of oral tumors.

14.
Cryobiology ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33279510

RESUMO

Our previous study revealed that melatonin (MLT) protected the quality of cryopreserved ovarian tissues in mice. This work was carried out to examine the role of MLT in inducing HSP90 expression of ovarian tissue for achieving cryoprotection. Pieces of ovarian tissues were obtained from 50 female rats treated with MLT at 0, 0.001, 0.01, 0.1, and 1 mM, respectively. After cryopreservation-thawing, HSP90 mRNA and protein level were evaluated using qRT-PCR and western blot. The qRT-PCR results revealed that HSP90 mRNA expression was significantly (p < 0.01) upregulated in MLT-treated groups in comparison with the controls (0 mM). Western blot revealed higher HSP90 protein expression in MLT-treated groups compared to control group (0 mM), thus further confirming that MLT positively affected HSP90 expression. Moreover, 0.1 mM MLT had better effects than other concentrations of MLT. Conclusively, findings in the present work provide a feasible technology for improving cryopreserved ovarian tissue quality through the addition of MLT to elicit HSP90 expression.

15.
Biomark Med ; 14(17): 1663-1677, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33336591

RESUMO

Aim: To study the expression patterns and prognostic value of the m6A-associated regulators in prostate adenocarcinoma (PRAD). Materials & methods: The mRNA expression and clinical data were downloaded from 'The Cancer Genome Atlas database'. The m6A-associated variants were downloaded from m6AVar database, and combined with 14 common m6A regulators for subsequent analysis. One-way analysis of variance, univariate Cox regression analysis and least absolute shrinkage and selection operator algorithm were successively applied to obtain the ultimate regulators and prognostic model. Finally, consensus clustering, protein-protein interaction (PPI) and enrichment analysis were performed. Result: Nine regulators were obtained. PRAD patients could be classified into two risk groups and subclasses with significant survival differences by the prognostic model and consensus clustering, respectively. Conclusion: All these nine regulators were related to prognosis in PRAD, and could be used as clinical biomarkers.

16.
Nat Genet ; 52(12): 1333-1345, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33230299

RESUMO

Genome-wide association studies identify genomic variants associated with human traits and diseases. Most trait-associated variants are located within cell-type-specific enhancers, but the molecular mechanisms governing phenotypic variation are less well understood. Here, we show that many enhancer variants associated with red blood cell (RBC) traits map to enhancers that are co-bound by lineage-specific master transcription factors (MTFs) and signaling transcription factors (STFs) responsive to extracellular signals. The majority of enhancer variants reside on STF and not MTF motifs, perturbing DNA binding by various STFs (BMP/TGF-ß-directed SMADs or WNT-induced TCFs) and affecting target gene expression. Analyses of engineered human blood cells and expression quantitative trait loci verify that disrupted STF binding leads to altered gene expression. Our results propose that the majority of the RBC-trait-associated variants that reside on transcription-factor-binding sequences fall in STF target sequences, suggesting that the phenotypic variation of RBC traits could stem from altered responsiveness to extracellular stimuli.

17.
J Agric Food Chem ; 68(45): 12558-12568, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33140649

RESUMO

In recent years, naturally occurring tetrahydro-ß-carboline (THC) alkaloids and their derivatives have been of biological interest. However, few studies and developments have reported the use of such structures in managing plant bacterial diseases. Herein, an array of novel THC derivatives containing an attractive 1,3-diaminopropan-2-ol pattern were prepared to evaluate the antiphytopathogen activity in vitro and in vivo and explore innovative antibacterial frameworks. Notably, target compounds exhibited excellent activities against three rebellious phytopathogens, namely, Pseudomonas syringae pv. actinidiae (Psa), Xanthomonas axonopodis pv. citri, and Xanthomonas oryzae pv. oryzae, at related optimal EC50 values of 2.39 (II9), 2.06 (I23), and 1.69 (II9) µg/mL, respectively. These effects were superior to those of the parent structure 1,2,3,4-THC and positive controls. In vivo assays showed that II9 exhibited excellent control efficiencies of 51.89 and 65.45% at 200 µg/mL against rice bacterial blight and kiwifruit bacterial canker, respectively, and I23 substantially relieved the citrus canker on the leaves. Antibacterial mechanisms indicated that these THC compounds could induce the increment of reactive oxygen species and subsequently endow the tested bacteria with distinct apoptotic behavior. In addition, II9 could alleviate the hypersensitive response and pathogenicity of Psa. Overall, these simple THC derivatives can be further developed as versatile antibacterial agents.

18.
Mar Genomics ; 54: 100785, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33222891

RESUMO

Faithful analysis of transcripts represents a critical component of the gene discovery, genomic characterization and annotation process in species without a reference genome. The present study generated 28,001 full-length transcripts of Misgurnus anguillicaudatus using the Pacific Bioscience (PacBio) single-molecule real-time (SMRT) sequencing system. A total of 77,346 consensus isoforms were identified, and 18,991 complete open reading frames (ORFs) detected. In total, 1345 lncRNAs were identified with high-confidence, with additional identification of a number of well-known transcription factors. The present study may facilitate additional exploration of the genomic signatures of M. anguillicaudatus.

19.
J Cell Mol Med ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33225580

RESUMO

Adoptive immunotherapy is a new potential method of tumour therapy, among which anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T cell), is a typical treatment agent for haematological malignancies. Previous clinical trials showed that the quality and phenotype of CAR-T cells expanded ex vivo would seriously affect the tumour treatment efficacy. Although magnetic beads are currently widely used to expand CAR-T cells, the optimal expansion steps and methods have not been completely established. In this study, the differences between CAR-T cells expanded with anti-CD3/CD28 mAb-coated beads and those expanded with cell-based aAPCs expressing CD19/CD64/CD86/CD137L/mIL-15 counter-receptors were compared. The results showed that the number of CD19-specific CAR-T cells with a 4-1BB and CD28 co-stimulatory domain was much greater with stimulation by aAPCs than that with beads. In addition, the expression of memory marker CD45RO was higher, whereas expression of exhausted molecules was lower in CAR-T cells expanded with aAPCs comparing with the beads. Both CAR-T cells showed significant targeted tumoricidal effects. The CAR-T cells stimulated with aAPCs secreted apoptosis-related cytokines. Moreover, they also possessed marked anti-tumour effect on NAMALWA xenograft mouse model. The present findings provided evidence on the safety and advantage of two expansion methods for CAR-T cells genetically modified by piggyBac transposon system.

20.
J Am Chem Soc ; 142(47): 20232-20239, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33190496

RESUMO

We studied the mechanisms of activation and stereoselectivity of a monofunctional Diels-Alderase (PyrI4)-catalyzed intramolecular Diels-Alder reaction that leads to formation of the key spiro-tetramate moiety in the biosynthesis of the pyrroindomycin family of natural products. Key activation effects of PyrI4 include acid catalysis and an induced-fit mechanism that cooperate with the unique "lid" feature of PyrI4 to stabilize the Diels-Alder transition state. PyrI4 enhances the intrinsic Diels-Alder stereoselectivity of the substrate and leads to stereospecific formation of the product.

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