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1.
RSC Adv ; 12(36): 23437-23446, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36090446

RESUMO

A silver nanoparticle-doped Zn(ii) metal-organic framework composite (AgNPs@ZnMOF) was investigated as an electrochemiluminescence (ECL) signal enhancer for potassium persulfate. First, ZnMOF was prepared by a one-step hydrothermal method, and then AgNPs@ZnMOF composite was obtained by depositing AgNPs on the surface and interior of ZnMOF. After the AgNPs@ZnMOF composite was modified on the glass carbon electrode (GCE), the cathode luminescence of potassium persulfate on bare GCE was enhanced by 8 times. A dual amplification mechanism provided by Zn(ii) and Ag nanoparticles in the AgNPs@ZnMOF composite has been validated by ECL spectra, fluorescence spectra, and electrochemical methods. The interaction between the sulfhydryl groups in l-cysteine (l-Cys) and AgNPs significantly affects the catalytic luminescence of the AgNPs@ZnMOF composite. Thus, a sensitive ECL method for the determination of l-Cys was developed based on the inhibition effect of l-Cys on the ECL signal within the linear range from 5.0 nM to 1.0 µM and the limit of detection was found to be 2 nM (S/N = 3). The established method has been successfully applied to the determination of l-Cys in human urine.

2.
Front Pediatr ; 10: 918136, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061378

RESUMO

Objective: To analyze the genotypic characteristics of patients with neurofibromatosis type 1 (NF1) associated dystrophic scoliosis and to summarize the outcomes of the surgical treatment of these patients. Methods: Exome sequencing (ES) combined with multiplex ligation-dependent probe amplification (MLPA) was used for genotypic identification. All patients underwent surgical treatments for spinal deformities, and the outcomes of the surgery was summarized by analyzing the clinical and imaging parameters before and after the surgery. Results: Fourteen patients (six males and eight females) were clinically diagnosed as NF1 associated dystrophic scoliosis with common symptoms including café-au-lait spots, paravertebral tumors, and dystrophic scoliosis. NF1 mutations were detected in 12 (85.7%) patients, including four nonsense mutations, three splicing mutations, three frameshift mutations, and two exon deletions. The first surgical procedure included growing-rod surgery in 10 patients and posterior spinal fusion in four patients. The follow-up duration was 2.3 years (1.0-10.3 years), and the Cobb angle of the main curve improved from 61.5° (30°-125°) pre-operatively to 14.5° (0°-42°) at the last follow-up, with an average correction rate of 74.0% (44-100%). Instrumentation-related complications occurred in four patients during the follow-up period. Conclusions: In patients with dystrophic scoliosis who met the clinical diagnostic criteria for NF1, the mutation detection rate of ES combined with MLPA was 85.7%. There was no mutation hotspot in NF1 gene, molecular diagnosis could offer information about genetic counseling, prenatal diagnosis and eugenics. Surgical treatment according to patient's age and severity could effectively correct the spinal deformities.

3.
Ann Hematol ; 101(10): 2271-2279, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35918462

RESUMO

P53 prognostic cut-off values differ between studies of mantle cell lymphoma (MCL), and its immunohistochemistry (IHC) interpretation is still based on semiquantitative estimation, which might be inaccurate. This study aimed to investigate the optimal cut-off value for p53 in predicting prognosis of patients with MCL and the possible use of computer image analysis to identify the positive rate of p53. We calculated p53 positive rate using QuPath software and compared it with the data obtained by manual counting and semiquantitative estimation. Survival curves were generated by using the Youden index and the Kaplan-Meier method. The chi-squared (χ2) test was used to compare MIPI, Ann Arbor stage, and cell morphology with p53. Spearman rank correlation test and Bland-Altman analysis were used to compare manual counting, computer image analysis and semiquantitative estimation, as well as the consistency between different observers. The optimal cut-off value of p53 for predicting prognosis was 20% in MCL patients. Patients with p53 ≥ 20% had a significantly worse overall survival (OS) than those with p53 < 20% (P < 0.0001). MCL patients with MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant cell morphology had more p53 ≥ 20%. There was a strong correlation between computer image analysis and manual counting of p53 from the same areas in MCL tissues (Spearman's rho = 0.966, P < 0.0001). The results of computer analysis are completely consistent between observers, and computer image analysis of Ki-67 can predict the prognosis of MCL patients. MCL patients with p53 ≥ 20% had a shorter OS and a tendency for MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant. Computer image analysis could determine the actual positive rate of p53 and Ki-67 and is a more attractive alternative than semiquantitative estimation in MCL.


Assuntos
Linfoma de Célula do Manto , Proteína Supressora de Tumor p53 , Adulto , Humanos , Processamento de Imagem Assistida por Computador , Antígeno Ki-67/análise , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/patologia , Prognóstico
4.
Water Sci Technol ; 86(3): 467-481, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35960831

RESUMO

Six kinds of dithiocarbamates (DTCs) were synthesized from three linear amines with different amino numbers, two polyether amines with different molecular weights, and one branched amine with benzene rings, respectively. The conditions affecting oil removal rate and floc rising time of DTC were studied using simulated oily wastewater. Furthermore, the effects of the molecular structure of DTC on oil removal efficiency, floc morphology, floc rising time, and floc adhesion were investigated. When the conditions were optimal, the oil removal efficiency of DTC synthesized from polyethylene polyamine was 95.14%, which was higher than other DTCs. Meanwhile, the ferrous ion was the most suitable chelating metal ion for DTC than other transition metal ions. The increase of amino groups in the initiators improves the oil removal efficiency of DTC, while the linear structural DTC exhibits a low oil removal efficiency due to a lack of network structural flocs. The introduction of polyether structure helps reduce the volume of the flocs and make them compact, but it also increases the adhesion of the floc on the metal surface. The introduction of bisphenol A phenol amino resin structure induces the generation of the flocs in oil wastewater and improves the oil removal efficiency.


Assuntos
Óleos , Águas Residuárias , Aminas , Floculação , Estrutura Molecular
5.
Medicine (Baltimore) ; 101(34): e30074, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36042646

RESUMO

In this study, we evaluated the clinical outcome of neutral wedge osteotomy assisted with the center of rotation of angulation (CORA) method of distal humerus anatomical axis for the treatment of cubitus varus deformity in children. From 2016 to 2019, 20 children with cubitus varus deformity after supracondylar fracture of the humerus were enrolled. Standard anteroposterior radiograph of the humerus was taken preoperatively. The CORA point and angulation angles were obtained by measuring the proximal and distal humerus anatomical axis. During the operation, neutral wedge osteotomy was performed to correct the varus deformity. The Baumann angle and the carrying angle were used to evaluate the correction effect of the distal humeral varus deformity. The average age of the patients was 7.8 years. Patients were followed up for an average of 29.3 months (range, 24-36 months). The average interval between surgery and injury was 12 months. The mean preoperative Baumann angle and carrying angle were 99° (90°-115°) and -14° (range, -10° to -30°), respectively. At the last follow-up, the mean Baumann angle and carrying angle was 76° (70°-80°) and 13.6° (10°-18°), respectively, with 16 cases showing excellent outcome and 4 cases showing good outcome. Our results indicated that the neutral wedge osteotomy assisted with CORA method of distal humerus anatomical axis showed good clinical outcomes in the treatment of cubitus varus deformity in children and is worthy of clinical application. The level of evidence is IV.


Assuntos
Articulação do Cotovelo , Fraturas do Úmero , Deformidades Articulares Adquiridas , Deformidades Congênitas dos Membros , Doenças Musculoesqueléticas , Criança , Articulação do Cotovelo/lesões , Articulação do Cotovelo/cirurgia , Humanos , Fraturas do Úmero/complicações , Fraturas do Úmero/cirurgia , Úmero/cirurgia , Deformidades Articulares Adquiridas/etiologia , Deformidades Articulares Adquiridas/cirurgia , Osteotomia/métodos , Amplitude de Movimento Articular , Resultado do Tratamento
6.
Front Med (Lausanne) ; 9: 941468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035411

RESUMO

Background: Congenital scoliosis (CS) is characterized by vertebral malformations. The precise etiology of CS is not fully defined. A compound inheritance of TBX6 was identified in 10% of patients with CS in Han Chinese and formed a distinguishable subtype named TBX6-associated congenital scoliosis (TACS). Methods: To investigate the variants and risk haplotype of TBX6, we recruited 121 patients with CS at Beijing Children's Hospital. We collected the clinical characteristics and surgical treatment options and followed their postoperative prognoses. Results: Eight patients (6.6%) were molecularly diagnosed with TACS and carried the previously defined pathogenic TBX6 compound heterozygous variants. All the eight patients with TACS had the typical TACS clinical feature of hemivertebrae in the lower part of the spine. These patients received posterior hemivertebra resection combined with segmental fusion. Follow-ups revealed satisfactory correction without postoperative complications. Conclusion: We observed a 6.6% prevalence of TACS in our CS cohort. Follow-ups further highlighted that surgical treatment of hemivertebra resection combined with segmental fusion performed well with prognosis for patients with TACS. This could provide valuable information for CS individuals with compound heterozygosity in TBX6.

7.
Virol Sin ; 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35934228

RESUMO

Enterovirus 71 (EV71) caused hand, foot and mouth disease (HFMD) is a serious threat to the health of young children. Although type I interferon (IFN-I) has been proven to control EV71 replication, the key downstream IFN-stimulated gene (ISG) remains to be clarified and investigated. Recently, we found that 2'-5'-oligoadenylate synthetases 3 (OAS3), as one of ISG of IFN-ß1b, was antagonized by EV71 3C protein. Here, we confirm that OAS3 is the major determinant of IFN-ß1b-mediated EV71 inhibition, which depends on the downstream constitutive RNase L activation. 2'-5'-oligoadenylate (2-5A) synthesis activity deficient mutations of OAS3 D816A, D818A, D888A, and K950A lost resistance to EV71 because they could not activate downstream RNase L. Further investigation proved that EV71 infection induced OAS3 but not RNase L expression by IFN pathway. Mechanically, EV71 or IFN-ß1b-induced phosphorylation of STAT1, but not STAT3, initiated the transcription of OAS3 by directly binding to the OAS3 promoter. Our works elucidate the immune regulatory mechanism of the host OAS3/RNase L system against EV71 replication.

8.
Proc Natl Acad Sci U S A ; 119(30): e2202650119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858429

RESUMO

Controlled reduction of oxygen is important for developing clean energy technologies, such as fuel cells, and is vital to the existence of aerobic organisms. The process starts with oxygen in a triplet ground state and ends with products that are all in singlet states. Hence, spin constraints in the oxygen reduction must be considered. Here, we show that the electron transfer efficiency from chiral electrodes to oxygen (oxygen reduction reaction) is enhanced over that from achiral electrodes. We demonstrate lower overpotentials and higher current densities for chiral catalysts versus achiral ones. This finding holds even for electrodes composed of heavy metals with large spin-orbit coupling. The effect results from the spin selectivity conferred on the electron current by the chiral assemblies, the chiral-induced spin selectivity effect.


Assuntos
Elétrons , Oxigênio , Catálise , Eletrodos , Transporte de Elétrons , Oxirredução , Oxigênio/química
9.
J Mater Chem B ; 10(28): 5454-5464, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35786741

RESUMO

The SARS-CoV-2 pandemic has become a severe global public health event, and the development of protective and therapeutic strategies is urgently needed. Downregulation of angiotensin converting enzyme 2 (ACE2; one of the important SARS-CoV-2 entry receptors) and aberrant inflammatory responses (cytokine storm) are the main targets to inhibit and control COVID-19 invasion. Silver nanomaterials have well-known pharmaceutical properties, including antiviral, antibacterial, and anticancer properties. Here, based on a self-established metal evaporation-condensation-size graded collection system, smaller silver particles reaching the Ångstrom scale (AgÅPs) were fabricated and coated with fructose to obtain a stabilized AgÅP solution (F-AgÅPs). F-AgÅPs potently inactivated SARS-CoV-2 and prevented viral infection. Considering the application of anti-SARS-CoV-2, a sterilized F-AgÅP solution was produced via spray formulation. In our model, the F-AgÅP spray downregulated ACE2 expression and attenuated proinflammatory factors. Moreover, F-AgÅPs were found to be rapidly eliminated to avoid respiratory and systemic toxicity in this study as well as our previous studies. This work presents a safe and potent anti-SARS-CoV-2 agent using an F-AgÅP spray.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , COVID-19/tratamento farmacológico , Humanos , Peptidil Dipeptidase A/metabolismo , SARS-CoV-2 , Prata/farmacologia
10.
J Mater Chem B ; 10(29): 5602-5611, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35801534

RESUMO

Amyloid-related diseases, such as Alzheimer's disease, are all considered to be related to the deposition of amyloid fibrils in the body. Insulin is a protein hormone that easily undergoes aggregation and fibrillation to form more toxic amyloid-like fibrils. So far, it is still challenging to develop a new protocol to study the ex situ detection and in situ inhibition of amyloid fibrillation. Here, we reported a modular synthetic strategy to construct nine amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles (FONs, TPE2/3/4X, X = G, M or S) with glucosamine (G), mannose (M) or sialic acid (S) as a hydrophilic moiety and tetraphenylethylene (TPE) as a hydrophobic AIE core. The carbohydrate-protein interactions between insulin and TPE2/3/4X were investigated by fluorescence spectroscopy, circular dichroism spectroscopy and transmission electron microscopy. Among the nine FON AIEgens, TPE2G was screened out as the best dual functional FON for the ex situ detection and in situ inhibition of the insulin fibrillation process, indicating that the glycosyl moiety exhibited a crucial effect on the detection/inhibition of insulin fibrillation. The molecular dynamics simulation results showed that the binding mechanism between TPE2G and native insulin was through weak interactions dominated by van der Waals interactions and supplemented by hydrogen bonding interactions to stabilize an α-helix of the insulin A chain, thereby inhibiting the insulin fibrillation process. This work provides a powerful protocol for the further research of amyloid-related diseases based on carbohydrate-protein interactions.


Assuntos
Amiloide , Nanopartículas , Amiloide/química , Proteínas Amiloidogênicas , Insulina/química , Insulina Regular Humana , Nanopartículas/química , Açúcares
11.
Front Genet ; 13: 849422, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711924

RESUMO

Diffuse large B cell lymphoma (DLBCL) is a group of biologically heterogeneous tumors with different prognoses. The tumor microenvironment plays a vital role in the tumorigenesis and development of DLBCL, and activated memory CD4+ T cells are an essential component of immunological cells in the lymphoma microenvironment. So far, there are few reports about activated memory CD4+T cells infiltration and related genes in the DLBCL tumor microenvironment. This study obtained the mRNA expression profile information of the testing GSE87371 dataset and another six validation datasets (GSE53786, GSE181063, GSE10846, GSE32918, GSE32018, GSE9327, GSE3892, TCGA-DLBC) from the GEO and TCGA databases. Weighted Gene Co-expression Network Analysis (WGCNA) screened gene module associated with activated memory CD4+ T cells infiltration. CIBERSORT and TIMER (immune cells infiltrating estimation analysis tools) were used to identify the relationship between activated memory CD4+ T cells and genes associated with immune infiltrating cells in the tumor microenvironment. The least absolute shrinkage and selection operator (LASSO) built the risk prediction model and verified it using nomogram and Kaplan-Meier analysis. Further functional characterization includes Gene Ontology, KEGG pathway analysis and Gene Set Enrichment Analysis (GSEA) to investigate the role and underlying mechanisms of these genes. These results suggest that the expression of FCER1G can reflect the invasion of activated memory CD4+ T cells in DLBCL, which provides a new idea for studying the tumor microenvironment and may become a potential predictive biomarker for the assessment of DLBCL.

12.
Front Immunol ; 13: 801727, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720286

RESUMO

Background: Results from our recent study demonstrate that sphingosine-1-phosphate receptor 1 (S1PR1) modulation improves microvascular hemodynamics after cerebrovascular thrombosis. This study was to determine the microvascular hemodynamic effects of a sub-thrombolytic dose of tPA combined with a selective S1PR1 modulator ozanimod in a mouse model of cerebrovascular thrombosis. Methods: Microvascular circulation in mice was monitored in vivo by two-photon microscopy. Thrombosis was induced in cortical arterioles by laser irradiation. Arteriolar flow velocity was measured by line-scanning following plasma-labeling with fluorescein-dextran. Results: Laser-induced thrombosis led to a persistent reduction of flow velocity in cortical arterioles. Sub-thrombolytic dose of tPA along with vehicle control did not improve the flow velocity in cortical arterioles following thrombosis. In contrast, a sub-thrombolytic dose of tPA along with ozanimod dramatically restored flow velocity in cortical arterioles following thrombosis. Ozanimod did not affect coagulation and bleeding time. Notably, ozanimod reduced thrombus volume without altering microvascular lumen diameter. In addition, ozanimod reduced leukocyte components within the thrombus. Conclusions: These findings demonstrate that the thrombolytic effect of a sub-thrombolytic dose of tPA is markedly enhanced by S1PR1 modulation, implying that S1PR1 modulation may improve the therapeutic benefit of low-dose tPA in patients with acute ischemic stroke.


Assuntos
AVC Isquêmico , Trombose , Animais , Fibrinolíticos/uso terapêutico , Humanos , Camundongos , Receptores de Esfingosina-1-Fosfato/efeitos dos fármacos , Terapia Trombolítica , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tecidual/farmacologia , Ativador de Plasminogênio Tecidual/uso terapêutico
13.
Front Microbiol ; 13: 887136, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756025

RESUMO

Magnetotactic bacteria (MTB) have been found in a wide variety of marine habitats, ranging from intertidal sediments to deep-sea seamounts. Deep-sea hydrothermal fields are rich in metal sulfides, which are suitable areas for the growth of MTB. However, MTB in hydrothermal fields have never been reported. Here, the presence of MTB in sediments from the Tangyin hydrothermal field was analyzed by 16S rRNA gene amplicon analysis, metagenomics, and transmission electron microscopy. Sequencing 16S rRNA gene yielded a total of 709 MTB sequences belonging to 20 OTUs, affiliated with Desulfobacterota, Alphaproteobacteria, and Nitrospirae. Three shapes of magnetofossil were identified by transmission electron microscopy: elongated-prismatic, bullet-shaped, and cuboctahedron. All of these structures were composed of Fe3O4. A total of 121 sequences were found to be homologous to the published MTB magnetosome-function-related genes, and relevant domains were identified. Further analysis revealed that diverse MTB are present in the Tangyin hydrothermal field, and that multicellular magnetotactic prokaryote (MMPs) might be the dominant MTB.

14.
Int J Chron Obstruct Pulmon Dis ; 17: 1365-1379, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711174

RESUMO

Purpose: Chronic obstructive pulmonary disease (COPD)-related pulmonary hypertension (PH) is one of the most common comorbidities of COPD, and often leads to a worse prognosis. Although the estimated prevalence and risk factors of COPD-related PH have been widely reported, these results have not been well integrated. This study aimed to review the worldwide incidence and prevalence of COPD-related PH and explore possible factors affecting its prevalence. Patients and Methods: We searched four electronic databases (Web of Science, Embase, Cochrane, and MEDLINE) to identify all observational studies on the prevalence of COPD-related PH from database creation until July 20, 2021. Eligibility screening, quality assessment, and data extraction of the retrieved studies were independently conducted by two reviewers. Meta-analyses were performed to determine the prevalence of PH in the COPD population. Random-effects meta-regression model analyses were conducted to investigate the sources of heterogeneity. Results: Altogether, 38 articles were included in the meta-analyses. The pooled prevalence was 39.2% (95% CI: 34.0-44.4, I 2 = 97.6%) for COPD-related PH. Subgroup analyses showed that the prevalence of PH increased with COPD severity, where the majority (30.2%) had mild PH and the minority had severe PH (7.2%). Furthermore, we found a significant regional difference in the prevalence of COPD-related PH (P = 0.000), which was the highest in Africa (64.0%) and the lowest in Europe (30.4%). However, stratified studies on other factors involving mean age, sex, enrolment time, participant recruitment settings, and PH diagnostic methods showed no significant differences in prevalence (P >0.05). Conclusion: The global incidence of PH in the COPD population is very high, and there are significant regional and international variations. Patients with COPD should be screened for PH and contributing risk factors to reduce the burden on individuals and society.


Assuntos
Hipertensão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Comorbidade , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Incidência , Prevalência , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia
15.
Mol Ecol ; 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35712997

RESUMO

Populus species have long been used as model organisms to study the adaptability of trees and the evolution of sex chromosomes. As a species belonging to the section Populus and limited to tropical areas, the P. qiongdaoensis genome contains important information for tropical poplar studies and protection. Here, we report a chromosome-level genome assembly and annotation of a female P. qiongdaoensis. Gene family clustering, positive selection detection and historical reconstruction of population dynamics revealed the tropical adaptation of P. qiongdaoensis, and showed convergent evolution with another tropical poplar, P. ilicifolia, at the molecular level, especially on some functional genes (e.g., PIF3 and PIL1). In addition, we also identified a ZW sex determination system on chromosome 19 of P. qiongdaoensis, and inferred that it seems to have a similar sex determination mechanism to other poplars, controlled by a type-A cytokinin response regulator (RR) gene. However, comparison and phylogenetic analysis of the sex determination regions confirmed a cryptic sex turnover event in the section Populus, which may be caused by the translocation and duplication of the RR gene driven by Helitron-like transposable elements. Our study provides new insights into the environmental adaptation and sex chromosome evolution of poplars, and emphasizes the importance of using long read sequencing in ecological and evolutionary inferences of plants.

16.
Leukemia ; 36(8): 2064-2075, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35697790

RESUMO

Extra-nodal NK/T-cell lymphoma, nasal type (ENKTCL) is a highly aggressive Epstein-Barr virus associated lymphoma, typically presenting in the nasal and paranasal areas. We assembled a large series of ENKTCL (n = 209) for comprehensive genomic analysis and correlative clinical study. The International Lymphoma Prognostic Index (IPI), site of disease, stage, lymphadenopathy, and hepatomegaly were associated with overall survival. Genetic analysis revealed frequent oncogenic activation of the JAK/STAT3 pathway and alterations in tumor suppressor genes (TSGs) and genes associated with epigenomic regulation. Integrated genomic analysis including recurrent mutations and genomic copy number alterations using consensus clustering identified seven distinct genetic clusters that were associated with different clinical outcomes, thus constituting previously unrecognized risk groups. The genetic profiles of ENTKCLs from Asian and Hispanic ethnic groups showed striking similarity, indicating shared pathogenetic mechanism and tumor evolution. Interestingly, we discovered a novel functional cooperation between activating STAT3 mutations and loss of the TSG, PRDM1, in promoting NK-cell growth and survival. This study provides a genetic roadmap for further analysis and facilitates investigation of actionable therapeutic opportunities in this aggressive lymphoma.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Perfil Genético , Genômica , Herpesvirus Humano 4 , Humanos , Células Matadoras Naturais/patologia , Linfoma Extranodal de Células T-NK/patologia , Linfoma de Células T Periférico/patologia
17.
Nat Cell Biol ; 24(7): 1129-1140, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35739318

RESUMO

RNA-mediated interference (RNAi) is a conserved mechanism that uses small RNAs (sRNAs) to silence gene expression. In the Caenorhabditis elegans germline, transcripts targeted by sRNAs are used as templates for sRNA amplification to propagate silencing into the next generation. Here we show that RNAi leads to heritable changes in the distribution of nascent and mature transcripts that correlate with two parallel sRNA amplification loops. The first loop, dependent on the nuclear Argonaute HRDE-1, targets nascent transcripts and reduces but does not eliminate productive transcription at the locus. The second loop, dependent on the conserved helicase ZNFX-1, targets mature transcripts and concentrates them in perinuclear condensates. ZNFX-1 interacts with sRNA-targeted transcripts that have acquired poly(UG) tails and is required to sustain pUGylation and robust sRNA amplification in the inheriting generation. By maintaining a pool of transcripts for amplification, ZNFX-1 prevents premature extinction of the RNAi response and extends silencing into the next generation.


Assuntos
Proteínas de Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , DNA Helicases/genética , Células Germinativas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
18.
Virol Sin ; 37(3): 418-426, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35504537

RESUMO

The global spread of enteroviruses (EVs) has become more frequent, severe and life-threatening. Intereron (IFN) I has been proved to control EVs by regulating IFN-stimulated genes (ISG) expression. 2'-5'-oligoadenylate synthetases 3 (OAS3) is an important ISG in the OAS/RNase L antiviral system. The relationship between OAS3 and EVs is still unclear. Here, we reveal that OAS3, superior to OAS1 and OAS2, significantly inhibited EV71 replication in vitro. However, EV71 utilized autologous 3C protease (3Cpro) to cleave intracellular OAS3 and enhance viral replication. Rupintrivir, a human rhinovirus 3C protease inhibitor, completely abolished the cleavage of EV71 3Cpro on OAS3. And the proteolytically deficient mutants H40G, E71A, and C147G of EV71 3Cpro also lost the ability of OAS3 cleavage. Mechanistically, the Q982-G983 motif in C-terminal of OAS3 was identified as a crucial 3Cpro cutting site. Further investigation indicated that OAS3 inhibited not only EV71 but also Coxsackievirus B3 (CVB3), Coxsackievirus A16 (CA16), Enterovirus D68 (EVD68), and Coxsackievirus A6 (CA6) subtypes. Notably, unlike other four subtypes, CA16 3Cpro could not cleave OAS3. Two key amino acids variation Ile36 and Val86 in CA16 3Cpro might result in weak and delayed virus replication of CA16 because of failure of OAS and 3AB cleavage. Our works elucidate the broad anti-EVs function of OAS3, and illuminate a novel mechanism by which EV71 use 3Cpro to escape the antiviral effect of OAS3. These findings can be an important entry point for developing novel therapeutic strategies for multiple EVs infection.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , 2',5'-Oligoadenilato Sintetase/genética , 2',5'-Oligoadenilato Sintetase/metabolismo , 2',5'-Oligoadenilato Sintetase/farmacologia , Proteases Virais 3C , Nucleotídeos de Adenina , Antivirais/química , Antivirais/farmacologia , Enterovirus/metabolismo , Enterovirus Humano A/genética , Humanos , Ligases/farmacologia , Oligorribonucleotídeos , Peptídeo Hidrolases/farmacologia , Replicação Viral
19.
Microorganisms ; 10(5)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35630369

RESUMO

Multicellular magnetotactic prokaryotes (MMPs) are a unique group of magnetotactic bacteria that are composed of 10-100 individual cells and show coordinated swimming along magnetic field lines. MMPs produce nanometer-sized magnetite (Fe3O4) and/or greigite (Fe3S4) crystals-termed magnetosomes. Two types of magnetosome gene cluster (MGC) that regulate biomineralization of magnetite and greigite have been found. Here, we describe a dominant spherical MMP (sMMP) species collected from the intertidal sediments of Jinsha Bay, in the South China Sea. The sMMPs were 4.78 ± 0.67 µm in diameter, comprised 14-40 cells helical symmetrically, and contained bullet-shaped magnetite and irregularly shaped greigite magnetosomes. Two sets of MGCs, one putatively related to magnetite biomineralization and the other to greigite biomineralization, were identified in the genome of the sMMP, and two sets of paralogous proteins (Mam and Mad) that may function separately and independently in magnetosome biomineralization were found. Phylogenetic analysis indicated that the sMMPs were affiliated with Deltaproteobacteria. This is the first direct report of two types of magnetosomes and two sets of MGCs being detected in the same sMMP. The study provides new insights into the mechanism of biomineralization of magnetosomes in MMPs, and the evolutionary origin of MGCs.

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