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Regulation of chromatin structure and accessibility determines the transcription activities of genes, which endows the host with function-specific patterns of gene expression. Upon viral infection, the innate immune responses provide the first line of defense, allowing rapid production of variegated antiviral cytokines. Knowledge on how chromatin accessibility is regulated during host defense against viral infection remains limited. Our previous work found that the nuclear matrix protein SAFA surveilled viral RNA and regulated antiviral immune genes expression. However, how SAFA regulates the specific induction of antiviral immune genes remains unknown. Here, through integration of RNA-seq, ATAC-seq and ChIP-seq assays, we found that the depletion of SAFA specifically decreased the chromatin accessibility, activation and expression of virus induced genes. And mutation assays suggested that the RNA-binding ability of SAFA was essential for its function in regulating antiviral chromatin accessibility. RIP-seq results showed that SAFA exclusively bound with antiviral related RNAs following viral infection. Further, we combined the CRISPR-Cas13d mediated RNA knockdown system with ATAC-qPCR, and demonstrated that the binding between SAFA and according antiviral RNAs specifically mediated the openness of the corresponding chromatin and following robust transcription of antiviral genes. Moreover, knockdown of these associated RNAs dampened the accessibility of related genes in an extranuclear signaling pathway dependent manner. Interestingly, VSV infection cleaved SAFA protein at the C-terminus which deprived its RNA binding ability for immune evasion. Thus, our results demonstrated that SAFA and the interacting RNA products collaborated and remodeled chromatin accessibility to facilitate antiviral innate immune responses.
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Antivirales , Virosis , Cromatina/genética , Interacciones Huésped-Patógeno/genética , Humanos , Inmunidad Innata/genética , ARN ViralRESUMEN
BACKGROUND: Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. METHODS: Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. RESULTS: The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. CONCLUSIONS: Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.
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Antibacterianos , Farmacorresistencia Bacteriana , Enterococcus faecalis , Enterococcus faecium , Infecciones por Bacterias Grampositivas , Linezolid , Pruebas de Sensibilidad Microbiana , Secuenciación Completa del Genoma , Linezolid/farmacología , China/epidemiología , Humanos , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/epidemiología , Enterococcus faecium/genética , Enterococcus faecium/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/genética , Antibacterianos/farmacología , Estudios Retrospectivos , Enterococcus/efectos de los fármacos , Enterococcus/genética , Proteínas Bacterianas/genética , Genoma Bacteriano , Epidemiología Molecular , Centros de Atención Terciaria , GenómicaRESUMEN
The end-operation accuracy of the satellite-borne robotic arm is closely related to the satellite attitude control accuracy, and the influence of the vibration of the satellite's flexural structure on the satellite attitude control is not negligible. Therefore, a stable and reliable vibration frequency identification method of the satellite flexural structure is needed. Different from the traditional non-contact measurement and identification methods of large flexible space structures based on marker points or edge corner points, the condition of non-marker points relying on texture features can identify more feature points, but there are problems such as low recognition and poor matching of features. Given this, the concept of 'the comprehensive matching parameter' of scenes is proposed to describe the scene characteristics of non-contact optical measurement from the two dimensions of recognition and matching. The basic connotation and evaluation index of the concept are also given in the paper. Guided by this theory, the recognition accuracy and matching uniqueness of features can be improved by means of equivalent spatial transformation and novel relative position relationship descriptor. The above problems in non-contact measurement technology can be solved only through algorithm improvement without adding hardware devices. On this basis, the Eigensystem Realization Algorithm (ERA) method is used to obtain the modal parameters of the large flexible space structure. Finally, the effectiveness and superiority of the proposed method are verified by mathematical simulation and ground testing.
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Desert hedgehog (DHH) signaling has been reported to be involved in spermatogenesis and the self-renewal of spermatogonial stem cells (SSCs). However, the role of DHH in proliferation of spermatogonia including SSCs remains to be elucidated. Here, we report that Dhh from medaka (Oryizas latipes) (named as OlDhh) could directly mediate the proliferation of spermatogonia via Smoothened (Smo) signaling. Oldhh is 1362 bp in length and encodes 453 amino acid (aa) residues with more than 50% identity with the homologs in other species. It has expression predominantly restricted to testis. The soluble and tag-free 176-aa mature OlDhh (named as mOlDhh) were successfully obtained by fusing with the N-terminal tag of cleavable 6-histidine and small ubiquitin-related modifier and then removing the tag. Notably, mOlDhh significantly promoted the proliferation of SG3 (a spermatogonial stem cell line from medaka testis) in a dose-dependent manner and spermatogonia in testicular organ culture. Furthermore, the proliferation of SG3 in the presence of mOlDhh could be inhibited by Smo antagonist (cyclopamine) resulting in apoptosis. Additionally, mOlDhh significantly upregulated the expression of smo as well as the pluripotent-related genes bcl6b and sall4. These data suggest that Smo is an indispensable downstream component in the Dhh signaling pathway. In conclusion, our findings unambiguously demonstrate that Dhh could directly mediate the proliferation of spermatogonia through Smo signaling. This study provides new knowledge about the proliferation regulation of spermatogonia.
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Oryzias , Espermatogonias , Animales , Proliferación Celular , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Masculino , Oryzias/genética , Oryzias/metabolismo , Transducción de Señal , Espermatogénesis/fisiología , Espermatogonias/metabolismo , Testículo/metabolismoRESUMEN
IFN regulatory factor 3 (IRF3) is critical for the transcription of type I IFNs in defensing virus and promoting inflammatory responses. Although several kinds of posttranslational modifications have been identified to modulate the activity of IRF3, whether atypical ubiquitination participates in the function regulation, especially the DNA binding capacity of IRF3, is unknown. In this study, we found that the ovarian tumor domain containing deubiquitinase OTUD1 deubiquitinated IRF3 and attenuated its function. An atypical ubiquitination, K6-linked ubiquitination, was essential for the DNA binding capacity of IRF3 and subsequent induction of target genes. Mechanistically, OTUD1 cleaves the viral infection-induced K6-linked ubiquitination of IRF3, resulting in the disassociation of IRF3 from the promoter region of target genes, without affecting the protein stability, dimerization, and nuclear translocation of IRF3 after a viral infection. Otud1 -/- cells as well as Otud1 -/- mice produced more type I IFNs and proinflammatory cytokines after viral infection. Otud1 -/- mice were more resistant to lethal HSV-1 and VSV infection. Consistent with the former investigations that IRF3 promoted inflammatory responses in LPS-induced sepsis, Otud1 -/- mice were more susceptible to LPS stimulation. Taken together, our findings revealed that the DNA binding capacity of IRF3 in the innate immune signaling pathway was modulated by atypical K6-linked ubiquitination and deubiquitination process, which was regulated by the deubiquitinase OTUD1.
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Factor 3 Regulador del Interferón/metabolismo , Interferón Tipo I/metabolismo , Proteasas Ubiquitina-Específicas/metabolismo , Ubiquitinación/fisiología , Animales , Línea Celular , Células HEK293 , Herpes Simple/metabolismo , Herpesvirus Humano 1/patogenicidad , Humanos , Inmunidad Innata/fisiología , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas/fisiología , Estabilidad Proteica , Transducción de Señal/fisiologíaRESUMEN
Alcohol liver disease (ALD) is characterized by intestinal barrier disruption and gut dysbiosis. Dysfunction of E74-like ETS transcription factor 4 (ELF4) leads to colitis. We aimed to test the hypothesis that intestinal ELF4 plays a critical role in maintaining the normal function of intestinal barrier and gut homeostasis in a mouse model of ALD. Intestinal ELF4 deficiency resulted in dysfunction of the intestinal barrier. Elf4-/- mice exhibited gut microbiota (GM) dysbiosis with the characteristic of a larger proportion of Proteobacteria. The LPS increased in Elf4-/- mice and was the most important differential metabolite between Elf4-/- mice and WT mice. Alcohol exposure increased liver-to-body weight ratio, and hepatic inflammation response and steatosis in WT mice. These deleterious effects were exaggerated in Elf4-/- mice. Alcohol exposure significantly increased serum levels of TG, ALT, and AST in Elf4-/- mice but not in WT mice. In addition, alcohol exposure resulted in enriched expression of genes associated with cholesterol metabolism and lipid metabolism in livers from Elf4-/- mice. 16S rRNA sequencing showed a decrease abundance of Akkermansia and Bilophila in Elf4-/- mice. In conclusion, intestinal ELF4 is an important host protective factor in maintaining gut homeostasis and alleviating alcohol exposure-induced hepatic steatosis and injury.
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Hígado Graso Alcohólico , Hepatopatías Alcohólicas , Animales , Disbiosis/metabolismo , Etanol/metabolismo , Etanol/toxicidad , Hígado Graso Alcohólico/metabolismo , Homeostasis , Hígado/metabolismo , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/metabolismo , Ratones , Ratones Endogámicos C57BL , ARN Ribosómico 16S/genéticaRESUMEN
RNA and protein are interconnected biomolecules that can influence each other's life cycles and functions through physical interactions. Abnormal RNA-protein interactions lead to cell dysfunctions and human diseases. Therefore, mapping networks of RNA-protein interactions is crucial for understanding cellular processes and pathogenesis of related diseases. Different practical protein-centric methods for studying RNA-protein interactions have been reported, but few robust RNA-centric methods exist. Here, we developed CRISPR-based RNA proximity proteomics (CBRPP), a new RNA-centric method to identify proteins associated with an endogenous RNA of interest in native cellular context without pre-editing of the target RNA, cross-linking or RNA-protein complexes manipulation in vitro. CBRPP is based on a fusion of dCas13 and proximity-based labelling (PBL) enzyme. dCas13 can deliver PBL enzyme to the target RNA with high specificity, while PBL enzyme labels the surrounding proteins of the target RNA, which are then identified by mass spectrometry.
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Espectrometría de Masas/métodos , Mapeo de Interacción de Proteínas , Proteínas de Unión al ARN/metabolismo , ARN/metabolismo , Biotinilación , Células HEK293 , Humanos , Unión Proteica , ARN/genética , Proteínas de Unión al ARN/genética , Coloración y EtiquetadoRESUMEN
BACKGROUND Lung adenocarcinoma (LUAD) is a type of non-small cell carcinoma. Its pathogenesis is being explored and there is no cure for the disease. MATERIAL AND METHODS The Gene Expression Omnibus (GEO) was searched to obtain data on expression of messenger RNA. GEO2R, an interactive web tool, was used to calculate the differentially expressed genes (DEGs) in LUAD. All the DEGs from different datasets were imported into VENNY 2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html) to identify the intersection of the DEGs. An online analysis tool, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), was used to help understand the biological meaning of DEG enrichment in LUAD. Cytoscape 3.7.2 was used to perform centrality analysis and visualize hub genes and related networks. Furthermore, the prognostic value of the hub genes was evaluated with the Kaplan-Meier plotter survival analysis tool. RESULTS The GEO database was used to obtain RNA sequencing information for LUAD and normal tissue from the GSE118370, GSE136043, and GSE140797 datasets. A total of 376 DEGs were identified from GSE118370, 248 were identified from GSE136403, and 718 DEGs were identified from GSE140797. The 10 genes with the highest degrees of expression - the hub genes - were CAV1, TEK, SLIT2, RHOJ, DGSX, HLF, MEIS1, PTPRD, FOXF1, and ADRB2. In addition, Kaplan-Meier survival evaluation showed that CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 were associated with favorable outcomes for LUAD. CONCLUSIONS CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 are hub genes in the DEG interaction network for LUAD and are involved in the development of and prognosis for the disease. The mechanisms underlying these genes should be the subject of further studies.
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Adenocarcinoma del Pulmón/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Regulación Neoplásica de la Expresión Génica/genética , Expresión Génica/genética , Neoplasias Pulmonares/genética , Células A549 , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Biología Computacional/métodos , Bases de Datos Genéticas , Perfilación de la Expresión Génica/métodos , Ontología de Genes , Redes Reguladoras de Genes/genética , Humanos , Neoplasias Pulmonares/patología , Pronóstico , Mapas de Interacción de Proteínas , Análisis de SupervivenciaRESUMEN
Platelet factor 4 (PF4) is an anti-Plasmodium component of platelets. It is expressed in megakaryocytes and released from platelets following infection with Plasmodium Innate immunity is crucial for the host anti-Plasmodium response, in which type I interferon plays an important role. Whether there is cross-talk between innate immune signaling and the production of anti-Plasmodium defense peptides is unknown. Here we demonstrate that E74, like ETS transcription factor 4 (ELF4), a type I interferon activator, can help protect the host from Plasmodium yoelii infection. Mechanically, ELF4 binds to the promoter of genes of two C-X-C chemokines, Pf4 and pro-platelet basic protein (Ppbp), initiating the transcription of these two genes, thereby enhancing PF4-mediated killing of parasites from infected erythrocytes. Elf4-/- mice are much more susceptible to Plasmodium infection than WT littermates. The expression level of Pf4 and Ppbp in megakaryocytes from Elf4-/- mice is much lower than in those from control animals, resulting in increased parasitemia. In conclusion, our study uncovered a distinct role of ELF4, an innate immune molecule, in host defense against malaria.
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Quimiocinas CXC/inmunología , Proteínas de Unión al ADN/inmunología , Malaria/inmunología , Plasmodium yoelii/inmunología , Factor Plaquetario 4/inmunología , Factores de Transcripción/inmunología , Transcripción Genética/inmunología , Animales , Quimiocinas CXC/genética , Proteínas de Unión al ADN/genética , Malaria/genética , Malaria/patología , Ratones , Ratones Noqueados , Factor Plaquetario 4/genética , Factores de Transcripción/genética , Transcripción Genética/genéticaRESUMEN
A highly selective and sensitive molecularly imprinted electrochemiluminescence (MIECL) sensor was developed based on the multiwall carbon nanotube (MWCNT)-enhanced molecularly imprinted quantum dots (MIP-QDs) for the rapid determination of cyfluthrin (CYF). The MIP-QDs fabricated by surface grafting technique exhibited excellent selective recognition to CYF, resulting in a specific decrease of ECL signal at the MWCNT/MIP-QD modified electrode. Under optimal conditions, the MIECL signal was proportional to the logarithm of the CYF concentration in the range of 0.2 µg/L to 1.0 × 103 µg/L with a determination coefficient of 0.9983. The detection limit of CYF was 0.05 µg/L, and good recoveries ranging from 86.0% to 98.6% were obtained in practical samples. The proposed MIECL sensor provides a novel, rapid, high sensitivity detection strategy for successfully analyzing CYF in fish and seawater samples.
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Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. This study was performed to examine the effects of long noncoding RNA CPS1 intronic transcript 1 (CPS1-IT) on PAH in rat models of obstructive sleep apnea (OSA) through regulating interleukin (IL)-1ß expression. The OSA models were induced in rats, for determination of the CPS1-IT expression. The binding of CPS1-IT and hypoxia-inducible factor 1 (HIF1) was verified. To analyze the effects of CPS1-IT on PAH, the overexpression vector of CPS1-IT and HIF1, shRNA against IL-1ß and pyrrolidine dithiocarbamate (PDTC, inhibitor of the NF-κB signaling pathway) were injected into rat models, respectively. The blood pressure and activity of biochemical indicators including nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), and lipid peroxide (LPO) were assessed. The expression of IL-1ß, HIF1, α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), and fibronectin (FN) was determined. The relationship of CPS1-IT to IL-1ß and NF-κB was evaluated. CPS1-IT was downregulated in the OSA rat model. Overexpressed CPS1-IT increased the activity of NO, NOS, and SOD as well as α-SMA expression, whereas decreasing LPO activity and expression of PCNA and FN, whereby PAH was suppressed. Notably, overexpressed CPS1-IT reduced IL-1ß expression through NF-κB signaling pathway via inhibiting the HIF1 transcriptional activity, suggesting a mechanism affecting PAH. To conclude, overexpressed CPS1-IT alleviated PAH in OSA by reducing IL-1ß expression, the mechanism of which was involved with inhibited HIF1 transcriptional activity and the NF-κB signaling pathway.
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Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Interleucina-1beta/genética , Hipertensión Arterial Pulmonar/genética , ARN Largo no Codificante/genética , Apnea Obstructiva del Sueño/genética , Actinas/genética , Animales , Carbamoil-Fosfato Sintasa (Amoniaco)/genética , Regulación de la Expresión Génica , Humanos , Peróxidos Lipídicos/genética , FN-kappa B/antagonistas & inhibidores , Óxido Nítrico/genética , Óxido Nítrico Sintasa/genética , Antígeno Nuclear de Célula en Proliferación/genética , Prolina/análogos & derivados , Prolina/farmacología , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/patología , ARN Interferente Pequeño/genética , Ratas , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/patología , Superóxido Dismutasa/genética , Tiocarbamatos/farmacologíaRESUMEN
OBJECTIVES: To examine the pregnancy outcomes of rabbits being subjected to pulmonary ventilation perfusion imaging examinations. METHODS: Pregnant rabbits were randomly divided into two groups: control group and experimental (lung ventilation-perfusion scintigraphy) group.The pregnancy outcomes were measured using indicators of miscarriage,premature birth,and stillbirth,as well as malformations and developmental abnormalities of offspring over a three-month period. RESULTS: No significant differences in miscarriage,premature birth,and stillbirth were found between the two groups.No obvious deformity appearances in the offspring were observed.The two groups showed no statistically significant differences in fetal progeny-intrauterine growth and developmental indicators measured by body mass,head circumference,abdominal circumference and length. CONCLUSIONS: Lung ventilation-perfusion scintigraphy examination has no effects on pregnant outcomes measured by miscarriage,premature birth,stillbirth,fetal teratogenicity and fetal growth.
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Pulmón/diagnóstico por imagen , Imagen de Perfusión/efectos adversos , Resultado del Embarazo , Animales , Femenino , Feto , Embarazo , Complicaciones del Embarazo , ConejosRESUMEN
Two new sesquiterpenoids, pinnatifone A (1) and pinnatifone B (2), and two new lignans, pinnatifolin (3) and isopinnatifolin (4), along with six known lignans (5-10), were isolated from the roots of Syringa pinnatifolia. The structures of the new compounds were elucidated by extensive spectroscopic methods, including NMR, MS, UV, and IR spectra. The lignans were screened for their anti-oxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH) assay). Most of them showed potent anti-oxidant activity, especially compound 5, whose potent anti-oxidant activity had an SC50 value higher than that of the positive control vitamin C.
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Lignanos/química , Sesquiterpenos/química , Syringa/química , Cristalografía por Rayos X , Lignanos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conformación Molecular , Exudados de Plantas/química , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Sesquiterpenos/aislamiento & purificación , Syringa/metabolismoRESUMEN
BACKGROUND: This study aimed to identify prognostic factors for pregnancy outcomes and construct a prognostic model for pregnancy outcomes in women with Recurrent Spontaneous Abortions (RSA) treated with cyclosporin A. METHODS: A total of 154 RSA patients treated with cyclosporin A between October 2016 and October 2018 were retrospectively recruited. Multivariate logistic regression was applied to identify the prognostic factors for pregnancy success in RSA women treated with cyclosporin A. The Receiver Operating Characteristic (ROC) curve was applied to construct prognostic value, and the prognostic performance was assessed using area under the ROC. RESULTS: After adjusting potential confounding factors, the authors noted increased age (OR = 0.771; 95 % CI 0.693â0.858; p < 0.001) and positive antinuclear antibodies (OR = 0.204; 95 % CI 0.079â0.526; p = 0.001) were associated with a reduced incidence of pregnancy success, while positive anti-ß2 glycoprotein-I-antibody (OR = 21.941; 95 % CI 1.176â409.281; p = 0.039) was associated with an increased incidence of pregnancy success after treated with cyclosporin A. The AUC of combining these variables for predicting pregnancy failure was 0.809 (95 % CI 0.735â0.880). CONCLUSIONS: This study systematically identified the prognostic factors for pregnancy success in women treated with cyclosporin A, and the constructed prognostic model based on these factors with relatively higher prognostic value. Further large-scale prospective studies should be performed to validate the prognostic value of the constructed model.
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Aborto Habitual , Ciclosporina , Inmunosupresores , Resultado del Embarazo , Humanos , Femenino , Embarazo , Ciclosporina/uso terapéutico , Adulto , Estudios Retrospectivos , Pronóstico , Aborto Habitual/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Curva ROC , Adulto JovenRESUMEN
Hemimasticatory spasm is a very rare disorder of the trigeminal nerve characterized by paroxysmal involuntary contraction of the jaw-closing muscles. Although its cause is not fully known, vascular compression of the trigeminal nerve is thought to be involved. Magnetic resonance imaging (MRI) can indicate continuing vascular compression for hemimasticatory spasm. Here, we report a case of hemimasticatory spasm that was caused by single venous compression of the trigeminal nerve root on MRI and was confirmed by microvascular decompression surgery.
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A Ni-catalyzed reductive dialkylation of 8-aminoquinoline-tethered aliphatic alkenes with two unactivated alkyl electrophiles is disclosed here. Key to the development of this transformation is the combination of primary alkyl (pseudo)halides and secondary alkyl iodides that produce products in a single regioselective manner. The reaction exhibits good functional group compatibility, and its synthetic utility was demonstrated by the concise synthesis of the precursors of biologically relevant molecules.
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Fluxapyroxad (FX), a succinate dehydrogenase inhibitor fungicide, has been detected in global marine and aquatic organisms. However, as a new pollutant, its biotoxicity and ecological risks to marine aquatic organisms are unclear. The accumulation and elimination processes and toxic effects of FX on Larimichthys crocea (L. crocea) at environmental concentrations were assessed. FX (1.0 µg/L) was rapidly enriched and persisted prolonged in L. crocea muscle and FX is highly toxic to juvenile L. crocea with the 96 h LC50 of 245.0 µg/L. Furthermore, the toxic effects of FX on juvenile L. crocea and adults L. crocea were compared and analyzed. In contrast to those of adult L. crocea, juvenile L. crocea showed a stronger oxidative stress response and rescued liver damage in terms of antioxidant enzyme activity, energy supply, and liver damage to FX. Transcriptomic analysis also showed that drug metabolism was activated. In the adult L. crocea, the disturbance of the energy metabolism, oxidative respiration, TCA cycle, and lipid metabolism genes were firstly found. The results revealed the accumulation and elimination pattern and ecotoxicological hazards of FX to L. crocea, which provided important theoretical basis for the study of environmental risks caused by new pollutants to marine organisms.
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Amidas , Perciformes , Transcriptoma , Animales , Antioxidantes/metabolismo , Proteínas de Peces/metabolismo , Perfilación de la Expresión Génica , Estrés Oxidativo , Perciformes/fisiologíaRESUMEN
Succinate dehydrogenase inhibitor fungicides (SDHIs) are frequently detected in the marine environment. However, studies on the toxicity of SDHIs to marine organisms, Mytilus coruscus (M. coruscus), are poorly reported. Therefore, the antioxidant activities and metabolomic response of four SDHIs, namely, boscalid (BC), thifluzamide (TF), fluopyram (FO), and bixafen (BIX), to (M. coruscus), were comprehensively investigated. The antioxidant activity of BC and TF was significantly increased (p<0.05), whereas those of FO and BIX were significantly decreased. Furthermore, metabolite discriminations among M. coruscus to four SDHIs were illustrated by an untargeted metabolomics approach. A total of 52, 50, 93, and 129 differential metabolites were obtained for BC, TF, FO, and BIX. KEGG of the different metabolites show that the four SDHIs had differential effects on the metabolic pathways of M. coruscus. The current study demonstrated four SDHIs triggered glucose metabolism, lipid metabolism, tricarboxylic acid cycle, and oxidative phosphorylation processes and caused the disruption of nutrient and energy conversion processes in mussels. Finally, five biomarkers were screened by analyzing common differential metabolites that emerged from the four SDHI exposures, which could be used for risk assessment of marine ecosystem exposure to SDHIs. Our results demonstrated the use of metabolomics to understand the potential mechanisms of toxicity of four SDHIs to mussels and to identify potential targets for future targeted risk assessment.
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Benzamidas , Compuestos de Bifenilo , Fungicidas Industriales , Mytilus , Niacinamida/análogos & derivados , Piridinas , Animales , Fungicidas Industriales/toxicidad , Succinato Deshidrogenasa/metabolismo , Antioxidantes , Mytilus/metabolismo , Ácido Succínico , Ecosistema , SuccinatosRESUMEN
A sensitive and robust multiclass analytical method was established to simultaneously determine 55 antibiotics in aquatic products through liquid chromatography-tandem mass spectrometry. A simple one-step purification process was successfully developed, which combined post-acidic acetonitrile extraction directly by an enhanced matrix removal cartridge. This approach eliminated the need for solvent transition. The established method for 55 antibiotics achieved an excellent linear relationship with R2 values ≥ 0.9921 in the range of 0.05-200 µg/L. The quantitation limits ranged within 0.04-5.0 µg/kg. Satisfactory recoveries (76.2%-99.7 %) were achieved with the relative standard deviations below 13.9 %. Furthermore, the antibiotic residues in aquatic products were analyzed, and the health and antibiotic resistance risk assessments were conducted. Although the health risks of target antibiotics were acceptable, a resistance risk was observed. Therefore, monitoring antibiotic residue levels in aquatic products requires considerable attention and further research to ensure the quality of marine products and consumer safety.
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Antibacterianos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Antibacterianos/análisis , Cromatografía Líquida de Alta Presión/métodos , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/aislamiento & purificación , Animales , PecesRESUMEN
Fluxapyroxad (FX), a typical succinate dehydrogenase inhibitor fungicide, is causing increased global concerns due to its fungicide effects. However, the accumulation and grow toxicity of FX to Litopenaeus vannamei (L. vannamei) is poorly understand. Therefore, the accumulation pattern of FX in L. vannamei was investigated for the first time in environmental concentrations. FX accumulated rapidly in shrimp muscle. Meanwhile, growth inhibition was observed and the mechanism derived by primarily accelerated glycolipid metabolism and reduced glycolipid content. Moreover, exposure to environmental concentrations of FX induced significant growth inhibition and oxidative stress and inhibited oxidative phosphorylation and TCA cycle in L. vannamei. The endocytosis signaling pathway genes were activated, thereby driving growth toxicity. Oxidative phosphorylation and cytosolic gene expression were further rescued in elimination experiments, demonstrating the mechanism of growth toxicity by FX exposure. The results revealed that FX persistently altered the gut microbiome of L. vannamei using gut microbiome sequencing, particularly with increased Garcinia Purple Pseudoalteromonas luteoviolacea for organic pollutant degradation. This study provided new insights into the potential toxicity of FX to marine organisms, emphasizing the need for further investigation and potential regulatory considerations.