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1.
J Phys Chem Lett ; : 9011-9019, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515494

RESUMO

The cubic-phase antimony trioxide (α-Sb2O3) is a room-temperature stable molecular crystal, composed of cage-like tetraantimony hexoxide (Sb4O6) molecules. Despite its versatile functionality, the van der Waals (vdW) bond-dominated nanomechanics is still unclear. Here, the bending plate-like linear behaviors of high-quality α-Sb2O3 nanoflakes were observed using the nanoindentation method. It is found that the cage-molecular crystal owns a very low in-plane Young's modulus of 14.9 ± 0.8 GPa and a remarkable maximum tensile strain of 6.0-8.8%, corresponding to a rupture strength of 0.89-1.31 GPa. Elucidated by the atomistic simulations, the compliant elastic modulus and the unexpectedly strong rupture strain are associated with the high-symmetry vdW bonding structure. The vdW nanomechanics is of fundamental and technological relevance to nanoelectronics.

2.
Neurosci Bull ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34523068

RESUMO

A large number of putative risk genes for autism spectrum disorder (ASD) have been reported. The functions of most of these susceptibility genes in developing brains remain unknown, and causal relationships between their variation and autism traits have not been established. The aim of this study was to predict putative risk genes at the whole-genome level based on the analysis of gene co-expression with a group of high-confidence ASD risk genes (hcASDs). The results showed that three gene features - gene size, mRNA abundance, and guanine-cytosine content - affect the genome-wide co-expression profiles of hcASDs. To circumvent the interference of these features in gene co-expression analysis, we developed a method to determine whether a gene is significantly co-expressed with hcASDs by statistically comparing the co-expression profile of this gene with hcASDs to that of this gene with permuted gene sets of feature-matched genes. This method is referred to as "matched-gene co-expression analysis" (MGCA). With MGCA, we demonstrated the convergence in developmental expression profiles of hcASDs and improved the efficacy of risk gene prediction. The results of analysis of two recently-reported ASD candidate genes, CDH11 and CDH9, suggested the involvement of CDH11, but not CDH9, in ASD. Consistent with this prediction, behavioral studies showed that Cdh11-null mice, but not Cdh9-null mice, have multiple autism-like behavioral alterations. This study highlights the power of MGCA in revealing ASD-associated genes and the potential role of CDH11 in ASD.

3.
Biomacromolecules ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516089

RESUMO

In this work, we establish a quantitative correlation between molecular release and material degradation. We characterize a radical-initiated photopolymerized hydrogel and base-initiated Michael addition-polymerized hydrogel, which form gels through distinct crosslinking reactions. Both scaffolds use the same degradable peptide crosslinker, which enables them to be degraded through the same enzymatic degradation reaction. A fluorescently labeled poly(ethylene glycol) molecule is chemically conjugated into the scaffold and is released during enzymatic degradation. Real-time changes in scaffold rheological properties during degradation are measured using bulk rheology. Molecular release is measured by quantifying the change in fluorescence in the incubation liquid and the hydrogel scaffold. A complicating factor, previously described in the literature, is that shear may cause increased crosslinking, resulting in an increase in the storage modulus after initiation of degradation, which changes release profiles by limiting the initial release of molecules. Therefore, we also test the hypothesis that shear induces additional crosslinking in degrading hydrogel scaffolds. To determine whether shear changes rheological properties during scaffold degradation, enzymatic degradation is characterized using bulk rheology as materials undergo continuous or minimal shear. To determine the effect of shear on molecular release, shear is induced by shaking the material during incubation. Release is characterized from scaffolds that are incubated with continuous or without shaking. We determine that shear does not make a difference in scaffold degradation or release regardless of the gelation reaction. Instead, we determine that the type of hydrogel crosslinking reaction greatly affects both material degradation and molecular release. A hydrogel crosslinking by base-initiated Michael addition does undergo further crosslinking at the start of degradation. We correlate release with enzymatic degradation for both scaffolds. We determine that the material storage modulus is indirectly correlated with release during degradation. These results indicate that rheological characterization is a useful tool to characterize and predict the release of molecules from degrading hydrogels.

5.
Mol Ther ; 29(9): 2754-2768, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34365033

RESUMO

Circular RNAs (circRNAs) represent a large group of non-coding RNAs that are widely detected in mammalian cells. Although most circRNAs are generated in a sense orientation, there is a group of circRNAs that are synthesized in an antisense orientation. High-throughput analysis of breast cancer specimens revealed a significant enrichment of 209 antisense circRNAs. The tumor suppressor SCRIB was shown to potentially produce thirteen circRNAs, three of which are in an antisense orientation. Among these three circRNAs, circSCRIB (hsa_circ_0001831) was the most enriched in the breast cancer panel. This antisense SCRIB circRNA was shown to span one intron and two exons. We hypothesized that this circRNA could decrease pre-mRNA splicing and mRNA translation. To test this, we generated a hsa_circ_0001831 expression construct. We found that there was decreased SCRIB mRNA production but increased cancer cell proliferation, migration, and invasion. In comparison, an exonic sequence construct did not affect mRNA splicing but decreased protein translation, leading to increased E-cadherin expression and decreased expression of N-cadherin and vimentin. Thus, there was increased cell migration, invasion, proliferation, colony formation, and tumorigenesis. Our study suggests a novel modulatory role of antisense circRNAs on their parental transcripts. This may represent a promising approach for developing circRNA-directed therapy.

6.
Genes (Basel) ; 12(8)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34440300

RESUMO

FGFR1 encodes a transmembrane cytokine receptor, which is involved in the early development of the human embryo and plays an important role in gastrulation, organ specification and patterning of various tissues. Pathogenic FGFR1 variants have been associated with Kallmann syndrome and hypogonadotropic hypogonadism. In our congenital scoliosis (CS) patient series of 424 sporadic CS patients under the framework of the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study, we identified four unrelated patients harboring FGFR1 variants, including one frameshift and three missense variants. These variants were predicted to be deleterious by in silico prediction and conservation analysis. Signaling activities and expression levels of the mutated protein were evaluated in vitro and compared to that of the wild type (WT) FGFR1. As a result, the overall protein expressions of c.2334dupC, c.2339T>C and c.1261A>G were reduced to 43.9%, 63.4% and 77.4%, respectively. By the reporter gene assay, we observed significantly reduced activity for c.2334dupC, c.2339T>C and c.1261A>G, indicating the diminished FGFR1 signaling pathway. In conclusion, FGFR1 variants identified in our patients led to only mild disruption to protein function, caused milder skeletal and cardiac phenotypes than those reported previously.

7.
Oxid Med Cell Longev ; 2021: 2514947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413925

RESUMO

MicroRNA-27a (miR-27a) has been implicated in myocardial ischemia-reperfusion injury (MIRI), but the underlying mechanism is not well understood. This study is aimed at determining the role of miR-27a in MIRI and at investigating upstream molecules that regulate miR-27a expression and its downstream target genes. miR-27a expression was significantly upregulated in myocardia exposed to ischemia/reperfusion (I/R) and cardiomyocytes exposed to hypoxia/reoxygenation (H/R). c-Fos could regulate miR-27a expression by binding to its promoter region. Moreover, overexpression of miR-27a led to a decrease in cell viability, an increase in LDH and CK-MB secretion, and an increase in apoptosis rates. In contrast, suppression of miR-27a expression resulted in the opposite effects. ATPase family AAA-domain-containing protein 3A (ATAD3a) was identified as a target of miR-27a. miR-27a regulated the translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and H/R-induced apoptosis via the regulation of ATAD3a. It was found that inhibiting miR-27a in vivo by injecting a miR-27a sponge could ameliorate MIRI in an isolated rat heart model. In conclusion, our study demonstrated that c-Fos functions as an upstream regulator of miR-27a and that miR-27a regulates the translocation of AIF from the mitochondria to the nucleus by targeting ATAD3a, thereby contributing to MIRI. These findings provide new insight into the role of the c-Fos/miR-27a/ATAD3a axis in MIRI.

8.
Food Chem ; 369: 130894, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34455322

RESUMO

Fast and convenient matrix purification is an important prerequisite for high-throughput analysis of drug multiresidues in food. In this study, a silanized melamine sponge was prepared and first applied in the rapid determination of multiclass veterinary drugs in eggs by ultrahigh-performance liquid chromatography-tandem mass spectrometry. Within five seconds, fast, convenient and efficient matrix separation could be achieved through simple soaking and squeezing. Compared to other matrix adsorbents, the developed material demonstrated equivalent or better purification performance. Good validation results were obtained in terms of drug recoveries (61.5%~97.0%, relative standard deviation (RSD) ≤ 10.8%), and linearities (R2 ≥ 0.999), as well as low limits of quantitation (0.3 ~ 10.9 µg·kg-1) and detection (0.1 ~ 3.8 µg·kg-1). By analyzing 52 egg samples, high concentrations of ofloxacin, trimethoprim, metronidazole, and dimetridazole were found at 542.9, 121.2, 66.1 and 58.0 µg·kg-1, respectively. The silanized melamine sponge has shown its great potential for rapid analysis of multiclass residues in food safety.

9.
J Environ Sci (China) ; 107: 150-159, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34412778

RESUMO

The black soldier fly larvae (BSFL) have been successfully applied to treat various organic wastes. However, the impacts of heavy metals on antibiotic resistance in the BSFL guts are poorly understood. Here, we investigated the effect of copper (exposure concentrations of 0, 100 and 800 mg/kg) on the antibiotic and metal resistance profiles in BSFL guts. A total of 83 antibiotic resistance genes (ARGs), 18 mobile genetic elements (MGEs) and 6 metal resistance genes (MRGs) were observed in larval gut samples. Exposure to Cu remarkably reduced the diversity of ARGs and MGEs, but significantly enhanced the abundances of gut-associated ARGs and MRGs. The levels of MRGs copA, czcA and pbrT were dramatically strengthened after Cu exposure as compared with CK (increased by 2.8-13.5 times). Genera Enterococcus acted as the most predominant potential host of multiple ARG, MGE and MRG subtypes. Meanwhile, high exposure to Cu aggravated the enrichment of potential pathogens in BSFL guts, especially for Escherichia, Enterococcus and Salmonella species. The mantel test and procrustes analysis revealed that the gut microbial communities could be a key determinant for antibiotic and metal resistance. However, no significant positive links were observed between MGEs and ARGs or MRGs, possibly suggesting that MGEs did not play a crucial role in shaping the ARGs or MRGs in BSFL guts under the stress of Cu. These findings extend our understanding on the impact of heavy metals on the gut-associated antibiotic and metal resistome of BSFL.


Assuntos
Dípteros , Metais Pesados , Animais , Cobre/toxicidade , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Incidência , Larva , Metais Pesados/toxicidade
10.
Ecotoxicol Environ Saf ; 223: 112569, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352582

RESUMO

Transgenic-Bacillus thuringiensis (Bt) crops express insecticidal proteins, which can accumulate in plants and soil where they may influence microbial populations. The impact of Bt crops on bacterial communities has only been assessed under short-term, and results have been contradictory. Here, we analyzed the bacterial communities in three niches, rhizosphere soil (RS), root endosphere (RE) and leaf endosphere (LE), of three Bt rice and their non-Bt parental lines for three consecutive years by high-throughput sequencing. In principal coordinate analysis (PCoA) and PERMANOVA (Adonis) analysis, operational taxonomic units (OTUs) were clustered primarily by niche type and differed significantly in the RE and LE but not in the RS between each of three Bt lines compared with the non-Bt rice line, and not in each respective niche among the three Bt rice lines. The bacterial communities in the RS of different rice lines over the 3 years were clustered mainly by year rather than by lines. The differential bacterial taxa among the lines did not overlap between years, presumably because Cry proteins are rapidly degraded in the soil. A network analysis of RS bacterial communities showed that the network complexity and density for the three Bt rice lines did not decrease compared with those for the non-Bt line. In conclusion, our results demonstrated that bacterial communities differed significantly in RE and LE between Bt and non-Bt rice lines, but the differences were mild and transient, and had no adverse impact on RS over the 3 years. This study provides favorable evidence in support of the commercialization of Bt rice.


Assuntos
Bacillus thuringiensis , Oryza , Bacillus thuringiensis/genética , Proteínas de Bactérias/genética , Endotoxinas/genética , Proteínas Hemolisinas/genética , Oryza/genética , Plantas Geneticamente Modificadas , Rizosfera
11.
Toxicol Appl Pharmacol ; 427: 115668, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358556

RESUMO

Pharmacological postconditioning (PPC), drug intervention before or during the early minutes of reperfusion, could stimulate cardioprotection as ischemic postconditioning. In this study, we examined whether PPC with sappanone A (SA), a homoisoflavanone with potent antioxidant and anti-inflammatory activity, has a protective effect on myocardial ischemia reperfusion injury (MIRI), and explored the underlying mechanism. A MIRI model was established using the Langendorff method. After 30 min of ischemia, isolated rat hearts were treated with SA at the onset of reperfusion to stimulate PPC. The changes in myocardial infarct size, mitochondrial function, mitochondrial biogenesis, mitophagy, and mitochondrial fission and fusion were detected. The results showed that SA postconditioning decreased the myocardial infarct size, inhibited the release of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and cardiac troponin (cTnI), as well as improved cardiac function, enhanced myocardial ATP content and mitochondrial complex activity, and prevented the loss of mitochondrial membrane potential and opening of mitochondrial permeability transition pore (mPTP). Mechanistically, we found that SA was an AMP-activated protein kinase (AMPK) activator, and SA postconditioning could facilitate mitochondrial biogenesis by increasing mitochondrial DNA (mtDNA) copy number and the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α). In addition, it balanced mitochondrial dynamics by decreasing fission and increasing fusion, and enhanced mitophagy in an AMPK-dependent manner. Moreover, AMPK silencing abolished the cardioprotection of SA postconditioning. Collectively, our study demonstrated that SA postconditioning ameliorated MIRI and mitochondrial dysfunction by regulation of mitochondrial quality control via activating AMPK. This finding provides a new insight into pharmacological action and clinical use of SA.

12.
Intern Med J ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34405958

RESUMO

INTRODUCTION: Infliximab remains a mainstay for treatment of inflammatory bowel disease (IBD), but a long infusion duration and subsequent monitoring can be burdensome to patients and health care providers. We assessed the safety of accelerated infusions for standard and dose-intensified infliximab regimens, and the effect on patient satisfaction and potential cost savings. METHODS: Patients with IBD on a stable maintenance dose of infliximab and in clinical remission received one or more accelerated infusions; over 30 min if receiving standard-dose (5 mg/kg), or over 60 min if receiving dose-intensified infliximab (up to 10 mg/kg). Outcomes included incidence of reactions (acute or delayed), patient satisfaction, and potential cost savings. We also explored infliximab trough levels after one and three accelerated infusions. RESULTS: 52 patients who received 150 infusions were studied. Incidence of reactions to accelerated infusions was 3.3% (3 out of 89) with standard-dose and 0% (out of 61) with dose-intensified infliximab. Reactions were delayed, mild, and self-limiting. None requiring drug cessation. Patient satisfaction was improved with shortened infusion time as compared to the patients' previous experiences (p = 0.00002). Mean plasma trough level of infliximab reduced from 9.3 mg/L (± 4.9) to 7.9 mg/L (± 4.1) (p = 0.02) with accelerated infusions, but none developed anti-infliximab antibodies. Nursing cost savings were estimated as $123.52 and $247.04 per-patient per-year for standard and dose-intensified infliximab, respectively. CONCLUSION: Accelerated infliximab infusions for standard and dose-intensified regimens seems to be safe and improved patient satisfaction. Potential impact on drug trough levels requires further investigations. This article is protected by copyright. All rights reserved.

13.
J Vestib Res ; 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34366304

RESUMO

BACKGROUND: Unapparent saccades in video head impulse test (vHIT) are usually present in MD patients but tend to be ignored by the clinician. The result of vHIT is constantly questioned in MD patients due to a lack of uniform metrics. A more effective indicator is needed for indicating MD's pathological progress. OBJECTIVES: To get a comprehensive understanding of the nature and usability of saccades in different MD stages. METHODS: 118 patients diagnosed with unilateral MD were recruited in this study. Patient history, audiological examination, caloric test, vHIT were performed. We proposed 'raw saccades' to represent all showed wave peaks behind the head peak and named saccades by their appearance sequence: 1st saccade, 2nd saccade and 3rd saccade. An exploratory saccade analysis was executed to investigate the effectiveness of saccade attributes in identifying MD stages. RESULTS: MD patients have greater detectable 1st saccade than PR score as well as 2nd saccade. The time and velocity of the 1st saccade show high interaural variability (p = 0.028, p = 0.000 respectively). No statistical difference concerning the vHIT gain, PR score and 2nd saccade among stages could be recognized on both affected and contralateral sides. Multiple comparisons show the affected 1st saccade velocity and affected 1st saccade absolute velocity have stage-difference. At late stages (3&4), the affected 1st saccade is manifested as a speed increase, and this measure shows a relatively high correlation with MD stages compared to other vestibular indicators. CONCLUSION: The 1st saccade velocity on the affected side could indicate the MD disease process and severity.

14.
Biomolecules ; 11(7)2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34356663

RESUMO

Melanoma represents less than 5% of skin cancers, but is the most lethal, mainly because of its high-metastatic potential and resistance to various therapies. Therefore, it is important to develop effective treatments, especially chemotherapeutic drugs with cytotoxicity, anti-metastaticity, and few side effects. One such natural product is hispidulin, a flavone distributed in plants of the Asteraceae. Previous studies have demonstrated that hispidulin has various pharmacological benefits, such as anti-tumor, anti-inflammation, and anti-allergic effects. This study aims to explore the effects of hispidulin against melanoma in vitro and in vivo. Results revealed that hispidulin selectively decreased the cell viability of A2058 cells in a dose- and time-dependent manner. Hispidulin induced cells accumulated in the sub-G1 phase via activating caspase 8 and 9, increased cleaved caspase 3, and cleaved PARP expression. Hispidulin was able to decrease AKT and ERK phosphorylation, which facilitated cell growth and survival. Moreover, hispidulin promoted reactive oxygen species generation in cells and suppressed cell migration through downregulated matrix metalloproteinase-2 expression. Hispidulin significantly inhibited tumor growth in a xenograft model. Based on these results, hispidulin produces its anti-melanoma effects by inducing cancer cell apoptosis and reducing its migration. Therefore, we suggest hispidulin as a potent therapeutic candidate for melanoma treatment.

15.
Nat Genet ; 53(9): 1385-1391, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34373642

RESUMO

Cotton produces natural fiber for the textile industry. The genetic effects of genomic structural variations underlying agronomic traits remain unclear. Here, we generate two high-quality genomes of Gossypium hirsutum cv. NDM8 and Gossypium barbadense acc. Pima90, and identify large-scale structural variations in the two species and 1,081 G. hirsutum accessions. The density of structural variations is higher in the D-subgenome than in the A-subgenome, indicating that the D-subgenome undergoes stronger selection during species formation and variety development. Many structural variations in genes and/or regulatory regions potentially influencing agronomic traits were discovered. Of 446 significantly associated structural variations, those for fiber quality and Verticillium wilt resistance are located mainly in the D-subgenome and those for yield mainly in the A-subgenome. Our research provides insight into the role of structural variations in genotype-to-phenotype relationships and their potential utility in crop improvement.

16.
Zool Res ; 42(5): 606-613, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34387416

RESUMO

The genus Tropidophorus consists of small semi-aquatic lizards that dwell in lowland forest steams (Barbour, 1921; Bauer & Jackman, 2008). Here, we designate the neotype and re-describe T. guangxiensis Wen, 1992 based on newly collected topotypic specimens. We also describe a new subspecies from Xuefeng Mountain, Hongjiang County, Hunan Province, central South China. Based on two mitochondrial genes (12S rRNA and 16S rRNA), the phylogenetic position of T. guangxiensis is allocated for the first time. Additionally, our data strongly support that the new subspecies is phylogenetically closely related to T. g. guangxiensis. We also present a morphological identification key for known species and subspecies of Tropidophorus in China.


Assuntos
Lagartos/anatomia & histologia , Lagartos/classificação , Animais , Classificação , DNA/genética , Feminino , Genoma , Masculino , Filogenia , Especificidade da Espécie
17.
Int J Biol Macromol ; 187: 614-623, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34314797

RESUMO

Chitosan/polyvinyl alcohol (CS/PVA) porous aerogel microspheres with stable physicochemical properties were obtained by gelation and freeze-drying process, and modified by adding different content of polyvinyl alcohol (PVA) into the microspheres. The physicochemical properties of porous aerogel microspheres, including porosity, swelling degree, acid-base resistance and compression performance were compared with chitosan (CS) microspheres. The microspheres were characterized by scanning electronic microscopy, Fourier transform infrared spectra, X-ray diffraction and compression test. The results showed that the structure of hybrid aerogel microspheres could be controlled by adjusting the content of PVA. The increase of PVA content reduced the pore size of CS/PVA porous aerogel microspheres, promoted the roughness of the surface and formed more orderly pore distribution. The higher PVA content was, the greater the swelling degree of the CS/PVA porous microspheres was. Adding proper amount of PVA into the CS/PVA microspheres could improve their acid resistance, but reduce their alkali resistance. Furthermore, the porosity of CS/PVA microspheres containing 33.3% PVA was the highest (78.3%) and the best compression strength (0.0505 MPa) when compression depth was 60% of the maximum height.

18.
World Neurosurg ; 153: e428-e434, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34229100

RESUMO

BACKGROUND: Whether patients with minor traumatic intracranial hemorrhage (MTICH) require intensive care remains uncertain. This study aimed to identify the factors affecting the postinjury neurologic outcomes of patients with MTICH to determine optimal care. METHODS: We retrospectively reviewed the data of all patients with trauma discharged from a tertiary trauma center during a 2-year period and included adult patients with isolated MTICH. Patient Glasgow Outcome Scale (GOS) score at discharge was the primary outcome measurement. A GOS score of 4 or 5 was defined as a favorable outcome, and a score of 1-3 was considered an unfavorable outcome. We compared the clinical data between favorable and unfavorable outcome groups to determine the differences between groups. RESULTS: Of the 11,814 patients considered, we identified 534 patients who met the inclusion criteria. Older adults accounted for 35.4% of the study cohort. Only 4 complications (0.7%) and 1 mortality (0.2%) were observed during hospitalization. The number of patients who requiring brain surgery, transfusion, mechanical ventilation, pressor, or invasive monitor was 5 (0.9%), 5 (0.9%), 3 (5.6%), 0 (0%), and 0 (0%), respectively. After multivariate analysis, we discovered that comorbidities, brain surgery requirement, respiratory rate, and Trauma Injury Severity Score were strongly associated with patient GOS score at discharge. CONCLUSIONS: MTICH rarely resulted in permanent morbidity and mortality. Older patients exhibited higher incidences of MTICH and were at a higher risk for unfavorable outcomes.

19.
Mol Microbiol ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34278632

RESUMO

The infection and colonization of pathogenic fungi are often regulated by transcription factors. In our previous study, the zinc finger protein-encoding gene StMR1 was found to be highly expressed during the infection process of Setosphaeria turcica, the pathogen causing northern corn leaf blight. Evolutionary tree analysis showed that this gene was associated with regulatory factors of melanin synthesis. However, the regulatory mechanism of melanin synthesis and its effect on pathogenicity remain unclear. In this study, the function of StMR1 was analyzed by gene knockout. When the expression level of StMR1 in the mutants was significantly reduced, the colony color became lighter, the mycelia were curved and transparent, and the mutant showed a significant loss of pathogenicity. In addition, compared with wild-type, the accumulation of melanin decreased significantly in △Stmr1. RNA-seq analysis revealed 1,981 differentially expressed genes between the wild-type and knockout mutant, among which 39 genes were involved in melanin metabolism. qPCR revealed that the expression levels of 6 key genes in the melanin synthesis pathway were significantly reduced. ChIP-PCR and yeast one-hybrid assays confirmed that StMR1 directly binds to the promoters of St3HNR, St4HNR, StPKS, and StLAC2 in the DHN melanin synthesis pathway and regulates gene expression. The C2H2-type zinc fingers and Zn(Ⅱ)2Cys6 binuclear cluster in StMR1 was important for the binding to targets.

20.
Front Immunol ; 12: 687151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290708

RESUMO

Anti-disease breeding is becoming the most promising solution to cyprinid herpesvirus-3 (CyHV-3) infection, the major threat to common carp aquaculture. Virus challenging studies suggested that a breeding strain of common carp developed resistance to CyHV-3 infection. This study illustrates the immune mechanisms involved in both sensitivity and anti-virus ability for CyHV3 infection in fish. An integrative analysis of the protein-coding genes and long non-coding RNAs (lncRNAs) using transcriptomic data was performed. Tissues from the head kidney of common carp were extracted at days 0 (the healthy control) and 7 after CyHV-3 infection (the survivors) and used to analyze the transcriptome through both Illumina and PacBio sequencing. Following analysis of the GO terms and KEGG pathways involved, the immune-related terms and pathways were merged. To dig out details on the immune aspect, the DEGs were filtered using the current common carp immune gene library. Immune gene categories and their corresponding genes in different comparison groups were revealed. Also, the immunological Gene Ontology terms for lncRNA modulation were retained. The weighted gene co-expression network analysis was used to reveal the regulation of immune genes by lncRNA. The results demonstrated that the breeding carp strain develops a marked resistance to CyHV-3 infection through a specific innate immune mechanism. The featured biological processes were autophagy, phagocytosis, cytotoxicity, and virus blockage by lectins and MUC3. Moreover, the immune-suppressive signals, such as suppression of IL21R on STAT3, PI3K mediated inhibition of inflammation by dopamine upon infection, as well as the inhibition of NLRC3 on STING during a steady state. Possible susceptible factors for CyHV-3, such as ITGB1, TLR18, and CCL4, were also revealed from the non-breeding strain. The results of this study also suggested that Nramp and PAI regulated by LncRNA could facilitate virus infection and proliferation for infected cells respectively, while T cell leukemia homeobox 3 (TLX3), as well as galectin 3 function by lncRNA, may play a role in the resistance mechanism. Therefore, immune factors that are immunogenetically insensitive or susceptible to CyHV-3 infection have been revealed.

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