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Cell-passage-adapted strains of African swine fever virus (ASFV) typically exhibit substantial genomic alterations and attenuated virulence in pigs. We have indicated that the human embryonic kidney (HEK293T) cells-adapted ASFV strain underwent genetic alterations and the I7L gene in the right variable region was deleted compared with the ASFV HLJ/2018 strain (ASFV-WT). A recent study has revealed that the deletion of the I7L-I11L genes results in attenuation of virulent ASFV in vivo, but the underlying mechanism remains largely unknown. Therefore, we hypothesized that the deletion of the I7L gene may be related to the pathogenicity of ASFV in pigs. We generated the I7L gene-deleted ASFV mutant (ASFV-ΔI7L) and found that the I7L gene deletion does not influence the replication of ASFV in primary porcine alveolar macrophages (PAMs). Using transcriptome sequencing analysis, we identified that the differentially expressed genes in the PAMs infected with ASFV-ΔI7L were mainly involved in antiviral immune responses induced by interferon gamma (IFN-γ) compared with those in the ASFV-WT-infected PAMs. Meanwhile, we further confirmed that the I7L protein (pI7L) suppressed the IFN-γ-triggered JAK-STAT signaling pathway. Mechanistically, pI7L interacts with STAT1 and inhibits its phosphorylation and homodimerization, which depends on the tyrosine at position 98 (Y98) of pI7L, thereby preventing the nuclear translocation of STAT1 and leading to the decreased production of IFN-γ-stimulated genes. Importantly, ASFV-ΔI7L exhibited reduced replication and virulence compared with ASFV-WT in pigs, likely due to the increased production of IFN-γ-stimulated genes, indicating that pI7L is involved in the virulence of ASFV. Taken together, our findings demonstrate that pI7L is associated with pathogenicity and antagonizes the IFN-γ-triggered JAK-STAT signaling pathway via inhibiting the phosphorylation and homodimerization of STAT1 depending on the Y98 residue of pI7L and the Src homology 2 domain of STAT1, which provides more information for understanding the immunoevasion strategies and designing the live attenuated vaccines against ASFV infection.
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Vírus da Febre Suína Africana , Febre Suína Africana , Interferon gama , Fator de Transcrição STAT1 , Transdução de Sinais , Proteínas Virais , Animais , Vírus da Febre Suína Africana/patogenicidade , Suínos , Febre Suína Africana/virologia , Febre Suína Africana/metabolismo , Fator de Transcrição STAT1/metabolismo , Interferon gama/metabolismo , Fosforilação , Humanos , Proteínas Virais/metabolismo , Proteínas Virais/genética , Virulência , Células HEK293 , Replicação Viral , Janus Quinases/metabolismo , Macrófagos Alveolares/virologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/imunologiaRESUMO
The African swine fever virus (ASFV) type II topoisomerase (Topo II), pP1192R, is the only known Topo II expressed by mammalian viruses and is essential for ASFV replication in the host cytoplasm. Herein, we report the structures of pP1192R in various enzymatic stages using both X-ray crystallography and single-particle cryo-electron microscopy. Our data structurally define the pP1192R-modulated DNA topology changes. By presenting the A2+-like metal ion at the pre-cleavage site, the pP1192R-DNA-m-AMSA complex structure provides support for the classical two-metal mechanism in Topo II-mediated DNA cleavage and a better explanation for nucleophile formation. The unique inhibitor selectivity of pP1192R and the difunctional mechanism of pP1192R inhibition by m-AMSA highlight the specificity of viral Topo II in the poison binding site. Altogether, this study provides the information applicable to the development of a pP1192R-targeting anti-ASFV strategy.
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Vírus da Febre Suína Africana , Microscopia Crioeletrônica , DNA Topoisomerases Tipo II , Vírus da Febre Suína Africana/enzimologia , DNA Topoisomerases Tipo II/metabolismo , DNA Topoisomerases Tipo II/química , Animais , Cristalografia por Raios X , Suínos , Proteínas Virais/metabolismo , Proteínas Virais/química , Sítios de Ligação , Modelos Moleculares , Antivirais/farmacologia , Antivirais/químicaRESUMO
Research on 2D materials originally focused on the highly symmetrical materials like graphene, h-BN. Recently, 2D materials with low-symmetry lattice such as PdSe2 have drawn extensive attention, due to the interesting layer-dependent bandgap, promising mechanical properties and excellent thermoelectric performance, etc. In this work, the phonon thermal transport is studied in PdSe2 with a pentagonal fold structure. The thermal conductivity of PdSe2 flakes with different thicknesses ranging from few nanometers to several tens of nanometers is measured through the thermal bridge method, where the thermal conductivity increases from 5.04 W mk-1 for 60 nm PdSe2 to 34.51 W mk-1 for the few-layer one. The atomistic modelings uncover that with the thickness thinning down, the lattice of PdSe2 becomes contracted and the phonon group velocity is enhanced, leading to the abnormal increase in the thermal conductivity. And the upshift of the optical phonon modes contributes to the increase of the thermal conductivity as well by creating less acoustic phonon scattering as the thickness reduces. This study probes the interesting abnormal thickness-dependent thermal transport in 2D materials, which promotes the potential thermal management at nanoscale.
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The uneven electric field and slow Zn2+ desolvation lead to rapid dendrite growth during Zn plating and stripping, which severely deteriorates the performance of Zn metal anodes (ZMAs) in Zn-ion batteries (ZIBs). Although polymer-based artificial protective (PBAP) layers are widely applied to homogenize the electric field of ZMAs, they often fail to promote the desolvation process that eventually induces Zn dendrite growth. Herein, a bi-functional protective layer, comprising a finger-like porous matrix of polysulfone (PSF) and a hydroxyl-rich filler of agarose (AG), is constructed to suppress Zn dendrite growth. COMSOL simulation demonstrates the ZMAs with bi-functional protective layers (Zn@PSF/AG) exhibit uniform electric field and Zn2+ distribution. Besides, the Zn@PSF/AG has both low desolvation energy and nucleation overpotential, effectively promoting the desolvation of Zn2+. Therefore, the Zn@PSF/AG symmetric cell exhibits excellent cycling performance, achieving 4200 h at 1 mA cm-2/1 mAh cm-2 and 1000 h at 5 mA cm-2/5 mAh cm-2. When coupling with ZnxV2O5 (ZnVO) cathode, the ZnVOâZn@PSF/AG full cell shows similarly high cycling stability, maintaining 72% of its capacity after 7000 cycles at 10 A g-1. This research highlights the positive roles of PBAP layer with multi-functional matrix-filler structure in developing long-life ZIBs.
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Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.
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Xanthomonas spp. are plant pathogens known for significantly impacting crop yields. Among them, Xanthomonas albilineans (Xal) is notable for colonizing the xylem and causing sugarcane leaf scald disease. This study employed homologous recombination to mutate quorum sensing (QS) regulatory genes (rpf) to investigate their role in Xal pathogenicity. Deletions of rpfF (ΔrpfF), rpfC (ΔrpfC), and rpfG (ΔrpfG) led to reduced swarming, growth, and virulence. However, DSF supplementation restored swarming and growth in the ΔrpfF mutant. Deleting rpfC, rpfG, and rpfF also reduced twitching motility and affected Type IV Pilus (T4P) expression. Transcriptomic analysis revealed that ΔrpfF positively regulates flagellar genes. DSF supplementation in ΔrpfF (ΔrpfF-DSF) modulated the expression of flagellar, chemotaxis, and T4P genes. These findings elucidate the DSF-mediated swarming pathway in Xal and provide valuable insights into its regulatory mechanisms.
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BACKGROUND: Inappropriate pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are both linked to preterm birth (PTB); however, which one plays a dominant role in PTB risk is not yet sure. We aimed to evaluate the combined effect of pre-pregnancy BMI and GWG on the risk of PTB in singleton pregnancies conceived both spontaneously and through assisted reproductive technology (ART). METHODS: The data included all mothers (n = 17,540,977) who had a live singleton birth from the US National Vital Statistics System (NVSS) 2015-2019. Logistic regression models, quantile-g-computation, and generalized additive model were used to analyze the combined association of pre-pregnancy BMI and GWG with PTB. RESULTS: The singleton PTB rate was significantly higher in ART pregnancies (11.5%) than in non-ART pregnancies (7.9%). When compared to those women with pre-pregnancy normal weight and GWG within Institute of Medicine (IOM) guidelines, the highest PTB risk was observed in non-ART women with pre-pregnancy underweight and GWG below IOM guidelines (aOR 2.56; 95% CI 2.53-2.60) and in ART women with pre-pregnancy obese and GWG below IOM guidelines (aOR 2.56; 95%CI 2.36-2.78). GWG dominated the combined effect with its joint effect coefficient of - 0.281 (P < 0.05) in non-ART women and - 0.108 (P < 0.05) in ART women. CONCLUSIONS: Inappropriate GWG played a dominant role in increasing the risk of PTB in both non-ART and ART populations. Counseling regarding pre-pregnancy BMI and especially GWG appears to be even more crucial for pregnancies conceived via ART, given their impact on PTB.
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Ganho de Peso na Gestação , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Nascimento Prematuro/epidemiologia , Índice de Massa Corporal , Resultado da Gravidez , Técnicas de Reprodução Assistida/efeitos adversos , Peso ao NascerRESUMO
An appropriate detection network is required to extract building information in remote sensing images and to relieve the issue of poor detection effects resulting from the deficiency of detailed features. Firstly, we embed a transposed convolution sampling module fusing multiple normalization activation layers in the decoder based on the SegFormer network. This step alleviates the issue of missing feature semantics by adding holes and fillings, cascading multiple normalizations and activation layers to hold back over-fitting regularization expression and guarantee steady feature parameter classification. Secondly, the atrous spatial pyramid pooling decoding module is fused to explore multi-scale contextual information and to overcome issues such as the loss of detailed information on local buildings and the lack of long-distance information. Ablation experiments and comparison experiments are performed on the remote sensing image AISD, MBD, and WHU dataset. The robustness and validity of the improved mechanism are demonstrated by control groups of ablation experiments. In comparative experiments with the HRnet, PSPNet, U-Net, DeepLabv3+ networks, and the original detection algorithm, the mIoU of the AISD, the MBD, and the WHU dataset is enhanced by 17.68%, 30.44%, and 15.26%, respectively. The results of the experiments show that the method of this paper is superior to comparative methods such as U-Net. Furthermore, it is better for integrity detection of building edges and reduces the number of missing and false detections.
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The mite Sarcoptes scabiei is responsible for the emerging or re-emerging skin disease called scabies in humans and sarcoptic mange in animals. Essential oils represent an appealing alternative strategy for the control of Sarcoptes infections, but the commercial development of essential oils may be hampered by their inconsistency in efficacy due to their varied chemical compositions. In order to address this issue, we assessed the efficacy of six components (carvacrol, eugenol, geraniol, citral, terpinen-4-ol, and linalool) against S. scabiei. At a concentration of 0.5%, carvacrol presented the best miticidal efficacy, with a median lethal time (LT50) value of 6.7 min, followed by eugenol (56.3 min), geraniol (1.8 h), citral (6.1 h), terpinen-4-ol (22.3 h), and linalool (39.9 h). The LC50 values at 30 min for carvacrol, eugenol, and geraniol were 0.24, 0.79, and 0.91%, respectively. In conclusion, carvacrol, eugenol, and geraniol represent potential complementary or alternative agents for S. scabiei infections in humans or animals. Our study provides a scientific basis for the development of scabicidal products based on essential oils.
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Óleos Voláteis , Escabiose , Animais , Humanos , Sarcoptes scabiei , Óleos Voláteis/farmacologia , Eugenol/farmacologia , Escabiose/tratamento farmacológico , Terpenos/farmacologiaRESUMO
BACKGROUND: Xanthomonas is a genus of gram-negative bacterium containing more than 35 species. Among these pathogenic species, Xanthomonas albilineans (Xal) is of global interest, responsible for leaf scald disease in sugarcane. Another notable Xanthomonas species is Xanthomonas sachari (Xsa), a sugarcane-associated agent of chlorotic streak disease. RESULT: The virulence of 24 Xanthomonas strains was evaluated by disease index (DI) and Area Under Disease Progress Curve (AUDPC) in the susceptible inoculated plants (GT 46) and clustered into three groups of five highly potent, seven mild virulent, and twelve weak virulent strains. The highly potent strain (X. albilineans, Xal JG43) and its weak virulent related strain (X. sacchari, Xsa DD13) were sequenced, assembled, and annotated in the circular genomes. The genomic size of JG43 was smaller than that of DD13. Both strains (JG43 and DD13) lacked a Type III secretory system (T3SS) and T6SS. However, JG43 possessed Salmonella pathogenicity island-1 (SPI-1). More pathogen-host interaction (PHI) genes and virulent factors in 17 genomic islands (GIs) were detected in JG43, among which six were related to pathogenicity. Albicidin and a two-component system associated with virulence were also detected in JG43. Furthermore, 23 Xanthomonas strains were sequenced and classified into three categories based on Single Nucleotide Polymorphism (SNP) mutation loci and pathogenicity, using JG43 as a reference genome. Transitions were dominant SNP mutations, while structural variation (SV) is frequent intrachromosomal rearrangement (ITX). Two essential genes (rpfC/rpfG) of the two-component system and another gene related to SNP were mutated to understand their virulence effect. The mutation of rpfG resulted in a decrease in pathogenicity. CONCLUSION: These findings revealed virulence of 24 Xanthomonas strains and variations by 23 Xanthomonas strains. We sequenced, assembled, and annotated the circular genomes of Xal JG43 and Xsa DD13, identifying diversity detected by pathogenic factors and systems. Furthermore, complete genomic sequences and sequenced data will provide a theoretical basis for identifying pathogenic factors responsible for sugarcane leaf scald disease.
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Saccharum , Xanthomonas , Doenças das Plantas/microbiologia , Folhas de Planta/genética , Saccharum/microbiologia , Virulência/genética , Fatores de Virulência/genética , Xanthomonas/genéticaRESUMO
PURPOSE: To summarize the available evidence to explore the effect of different prophylactic cefazolin regimens on postoperative surgical site infection after cesarean section. METHODS: We searched WOS, Pubmed, and EMBASE Database also traced citations in the reference sections of the retrieved studies. English search words: Cesarean section, Surgical site infection, Cefazolin. The majority of the literature are randomized controlled trials comparing varied regimens of cefazolin. RESULTS: A total of 11 randomized controlled trials and 4 non-randomized controlled trials involving 16,328 pregnant women were eligible. There was no statistically significant difference in the risk of SSI after cesarean section when cefazolin was given at a high dose compared with cefazolin at a low dose (OR 0.77, 95% CI 0.57-1.04, I2 = 0.0%). The risk of SSI after cesarean section was reduced by prophylactic use of cefazolin before skin incision compared with that after the umbilical cord clamping (OR 0.48, 95% CI 0.29-0.82, I2 = 53.4%). Because of the extreme heterogeneity of the combined drug use, no meta-analysis results were provided. The consequences of cefazolin combined with other antibiotics (either orally or intravenously) vary widely. For pregnant women with different risk factors, cefazolin alone or the type, dose and drug route of cefazolin combined with additional antibiotics need to be further studied and explored. CONCLUSIONS: All in all, this article illustrates a better use of cefazolin for the control of Surgical incision site infection in the cesarean section. For pregnant women with cesarean section without high-risk factors of infection, the use of cefazolin is effective, but for pregnant women with different high-risk factors, the specific use of prophylactic antibiotics needs to be further explored.
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Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Infecções Bacterianas/prevenção & controle , Cefazolina/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Antibioticoprofilaxia/efeitos adversos , Cesárea/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Gravidez , Fatores de Risco , Infecção da Ferida Cirúrgica/prevenção & controleRESUMO
Essential oils and their components represent an appealing alternative strategy against parasitic mites. The chemical complexity and variability of essential oils limit their use and additional work is required to analyze the efficacy and application rate of essential oils' individual components. In the present study, the activity of five terpenes (terpinen-4-ol, citral, linalool, eugenol, and geraniol) was evaluated against Psoroptes cuniculi motile stages and eggs collected from naturally infected rabbits. Eugenol presented the best acaricidal efficacy with a median lethal concentration (LC50) value of less than 0.1% at 24 h, followed by geraniol (0.33%), linalool (0.38%), citral (0.46%), and terpinen-4-ol (0.66%). Geraniol and eugenol were able to kill all mites within 5 min at 1% concentration. The effective concentration to inhibit 50% (EC50) of egg hatching was 0.65%, 0.66%, 0.85%, 1.47%, and 2.87% for eugenol, geraniol, citral, terpinen-4-ol, and linalool, respectively. In conclusion, eugenol, geraniol, citral, terpinen-4-ol, and linalool should be considered as promising agents for the development of botanical acaricides against Psoroptes cuniculi.
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Acaricidas/farmacologia , Óleos Voláteis/farmacologia , Psoroptidae/efeitos dos fármacos , Terpenos/farmacologia , Animais , Dose Letal Mediana , Infestações por Ácaros/tratamento farmacológico , Infestações por Ácaros/parasitologia , Óvulo/efeitos dos fármacos , Testes de Sensibilidade Parasitária , CoelhosRESUMO
A new series of fluorinated 2,5-substituted 1-ethyl-1H-benzimidazole derivatives were synthesized from starting compounds 3a-i, which were prepared from acrylic acid ethyl ester and the appropriate amines using trifluoromethanesulfonic acid as a catalyst. A total of 9 novel derivatives were synthesized through 9 steps. All of them were evaluated for thrombin inhibition activity in vitro for the first time. We have altered their structures using different substituents on the amines to assess their structure-activity relationships as direct thrombin inhibitors. All the compounds were effective thrombin inhibitors, with IC50 values ranging from 3.39 to 23.30 nM. Among the compounds synthesized, compounds 14a, 14b, 14d, 14e, and 14h exhibited greater anticoagulant activity than argatroban (IC50 = 9.36 nM). Furthermore, compound 14h synthesized starting with 2-amino-pyridine was the most potent thrombin inhibitor with an IC50 value of 3.39 nM. Molecular modeling studies were performed to determine the probable interactions of the most potent compounds 14a, 14e, and 14h with their protein receptor (PDB ID: 1KTS). Docking data show that the active compounds inhibit thrombin in a similar mode to that of the potent anticoagulant dabigatran.
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Antitrombinas/síntese química , Antitrombinas/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/farmacologia , Arginina/análogos & derivados , Dabigatrana/farmacologia , Relação Dose-Resposta a Droga , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ácidos Pipecólicos/farmacologia , Relação Estrutura-Atividade , SulfonamidasRESUMO
BACKGROUND: Cardiac myxomas rarely occur in children or adolescents. In addition, it is even more rare for the adolescent patient to present with neurological symptoms only. Early diagnosis is difficult because the symptoms of left atrial myxoma are frequently nonspecific. If delayed or left undiagnosed, severe and fatal complications, such as systemic embolism, heart failure, and pulmonary hypertension, may occur. CASE REPORT: A 13-year-old girl was admitted to our resuscitation room because of loss of consciousness for the preceding 2 h; she had a longstanding history of headache and dizziness for the previous 18 months. Repeated investigations at her local hospital did not reveal any abnormalities. During this admission, routine chest x-ray study found an abnormal bulge of a segment of the pulmonary artery and elevated cardiac enzymes. Emergency bedside echocardiography was performed and revealed a myxoma in the left atria. Subsequent computed tomography head revealed cardiogenic cerebral embolism. When her condition was stable, the patient was taken to the operating room, where a tumorectomy was performed successfully. The patient was then treated with oral anticoagulants and an uneventful recovery was made. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In order to avoid delayed diagnosis and treatment of its potentially fatal complications, it is important for the emergency clinician to have a high level of suspicion for a cardiac myxoma when attending to young patients that present with syncope. We therefore recommend that, as routine practice, bedside echocardiography to be carried in the emergency department for young patients that present with syncope.
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Cefaleia/etiologia , Neoplasias Cardíacas/complicações , Embolia Intracraniana/diagnóstico , Mixoma/complicações , Adolescente , Feminino , Átrios do Coração , Neoplasias Cardíacas/diagnóstico , Humanos , Mixoma/diagnósticoRESUMO
In the past decade, research into growth and application of anodic titania nanotubes has been focused on planar titanium electrodes. Although patterned, curved, or cylindrical substrates were also employed in a number of applications, the study of nanotubes grown on a titanium tubular electrode is rather inadequate, despite their expected uses in thermal fluids. In this study, growth of titania nanotubes on tubular electrodes was investigated. It was found that nanotubes are formed at both outer and inner surfaces of the electrode. The nanotube length (or growth rate in the first 30 min) at the outer surface decreases gradually from the side facing the cathode to that at the other side, while the length at the inner surface smears out this trend. This is due to the effect of the electric field emanating from the potential drop in the organic electrolyte. The variation of nanotube diameter just echoes such a tendency of potential drop. The influence of electrode orientation during anodization on the resulting features of nanotubes was also examined and discussed. The nanotube geometry is thus tailorable for particular applications.
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In this study, 21 species of Hybos Meigen, 1803 are reviewed in Huaping National Nature Reserve, China. Among these, three species, i.e., Hybosdenticulatussp. nov., Hybosforcipatasp. nov. and H.paraterminalissp. nov., are described as new to science. In addition, nine known species of this genus are reported for the first time in Guangxi. All the known species were enumerated, and an identification key to the species of Hybos from Huaping National Nature Reserve based on morphological characteristics is provided.
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Obstructive sleep apnea (OSA) and urinary incontinence (UI) are two prevalent health conditions with significant impacts on individuals' quality of life. Although they appear distinct in nature, a growing body of evidence suggests a potential interrelationship between these conditions. Our objective was to explore the association between the risk of OSA and the occurrence of UI within a nationally representative sample of U.S. adults. Utilizing cross-sectional data from the National Health and Nutrition Examination Survey spanning the years 2015 to 2020, we conducted an analysis on a sample comprising 8,647 adults who provided comprehensive self-reported information on both UI and sleep apnea symptoms. The included cohorts were analyzed based on their sex. We employed the Multivariate Apnea Prediction (MAP) index to evaluate the risk of OSA. Subgroup analyses were conducted, categorizing them according to different types of UI. The association between OSA risk and UI was estimated through multivariable binary logistic regression models. After adjusting for relevant confounders, our results revealed a positive correlation between OSA risk and UI in both males (OR = 5.68, 95% CI = 1.74-18.47) and females (OR = 5.99, 95% CI = 2.68-13.41). The subgroup analysis illustrates that an elevated risk of OSA heightens the likelihood of experiencing stress urinary incontinence (SUI), urge urinary incontinence (UUI), and mixed urinary incontinence (MUI) in both male and female populations. Our study findings imply that an elevated risk of OSA exacerbates the likelihood of UI, SUI, UUI and MUI.
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Apneia Obstrutiva do Sono , Incontinência Urinária , Humanos , Masculino , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/complicações , Feminino , Incontinência Urinária/epidemiologia , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Fatores de Risco , Inquéritos Nutricionais , Idoso , Estados Unidos/epidemiologia , Prevalência , Qualidade de VidaRESUMO
Objective: This study aims to explore the causal relationship between inflammatory markers and myopia through the use of bidirectional Mendelian randomization (MR) and myopia animal models. Methods: The authors utilized data from a comprehensive and publicly accessible genome-wide association study (GWAS) for our analysis, which includes 460 536 European ancestry control subjects and 37 362 myopia patients. Utilizing a two-sample Mendelian randomization analysis framework, 27 inflammatory markers were investigated as exposure variables with myopia serving as the outcome variable. Nine MR analysis techniques were employed, with inverse-variance weighting (IVW) as the principal MR analysis method. Heterogeneity was assessed using Cochrane's Q test. The identification of single-nucleotide polymorphisms (SNPs) and outliers linked to myopia was achieved via MR-PRESSO. The expression of interleukin-2 (IL-2) in the vitreous of guinea pigs subjected to experimentally induced form-deprivation myopia (FDM) was examined. Results: Elevated concentrations of IL-2 and IL-2ra were found to be associated [IVW estimate odds ratio (OR): 1.003, 95% CI: 1.001-1.005, P=0.001] and strongly associated (IVW estimate OR: 1.002, 95% CI: 1.000-1.003, P=0.049) with an increased risk of myopia, respectively. Conversely, lower levels of C-reactive protein (CRP) (IVW estimate OR: 0.996, 95% CI: 0.994-0.999, P=0.002) and tumour necrosis factor alpha (IVW estimate OR: 0.995, 95% CI: 0.994-0.996, P<0.001) were robustly linked to a heightened risk of myopia. IL-2 expression was notably upregulated in the vitreous of guinea pigs with experimentally induced FDM. Conclusions: Elevated levels of inflammatory factors, especially IL-2 and IL-2ra, have a potential causal relationship with myopia susceptibility, providing new insights into the pathogenesis of myopia.
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Xanthomonas albilineans (Xal) is a gram-negative bacterial pathogen responsible for developing sugarcane leaf scald disease, which engenders significant economic losses within the sugarcane industry. In the current study, homologous recombination exchange was carried out to induce mutations within the virB/D4-like type IV secretion system (T4SS) genes of Xal. The results revealed that the virB11-deletion mutant (ΔvirB11) exhibited a loss in swimming and twitching motility. Application of transmission electron microscopy analysis further demonstrated that the ΔvirB11 failed to develop flagella formation and type IV pilus morphology and exhibited reduced swarming behaviour and virulence. However, these alterations had no discernible impact on bacterial growth. Comparative transcriptome analysis between the wild-type Xal JG43 and the deletion-mutant ΔvirB11 revealed 123 differentially expressed genes (DEGs), of which 28 and 10 DEGs were notably associated with flagellar assembly and chemotaxis, respectively. In light of these findings, we postulate that virB11 plays an indispensable role in regulating the processes related to motility and chemotaxis in Xal.
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Proteínas de Bactérias , Fímbrias Bacterianas , Flagelos , Xanthomonas , Xanthomonas/patogenicidade , Xanthomonas/genética , Virulência/genética , Fímbrias Bacterianas/metabolismo , Fímbrias Bacterianas/ultraestrutura , Fímbrias Bacterianas/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/genética , Regulação Bacteriana da Expressão Gênica , Morfogênese , Doenças das Plantas/microbiologia , Saccharum/microbiologiaRESUMO
Superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery represents the primary treatment for Moyamoya disease (MMD), with its efficacy contingent upon collateral vessel development. This study aimed to develop and validate a machine learning (ML) model for the non-invasive assessment of STA-MCA bypass surgery efficacy in MMD. This study enrolled 118 MMD patients undergoing STA-MCA bypass surgery. Clinical features were screened to construct a clinical model. MRI features were extracted from the middle cerebral artery supply area using 3D Slicer and employed to build five ML models using logistic regression algorithm. The combined model was developed by integrating the radiomics score (Rad-score) with the clinical features. Model performance validation was conducted using ROC curves. Platelet count (PLT) was identified as a significant clinical feature for constructing the clinical model. A total of 3404 features (851 × 4) were extracted, and 15 optimal features were selected from each MRI sequence as predictive factors. Multivariable logistic regression identified PLT and Rad-score as independent parameters used for constructing the combined model. In the testing set, the AUC of the T1WI ML model [0.84 (95% CI, 0.70-0.97)] was higher than that of the clinical model [0.66 (95% CI, 0.46-0.86)] and the combined model [0.80 (95% CI, 0.66-0.95)]. The T1WI ML model can be used to assess the postoperative efficacy of STA-MCA bypass surgery for MMD.