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1.
One Health ; 18: 100736, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38694616

RESUMEN

The growth in ecotourism and nature-based recreational activities in China has resulted in an increased frequency of visits to green spaces, thereby elevating exposure to ticks and the subsequent risk of tick-borne diseases. This study comprehensively investigate individual behavioral and cognitive factors associated with the risk of contracting tick-borne diseases to facilitate the development of effective prevention and control strategies, supporting public health initiatives in high-prevalence regions. We conducted an extensive questionnaire survey among 3000 residents from three northeastern provinces in China (Heilongjiang, Jilin, and Liaoning), where tick-borne diseases exhibit relatively high prevalence. The survey focused on gathering information regarding participants' tick bite history, perception of tick-borne disease risks, and outdoor activity patterns. Using structural equations analysis, we explored the pathways and strengths of the associations between these factors. Our findings revealed an average self-reported tick bite rate of 14% among the participants. Notably, tick-borne encephalitis exhibited the highest self-reported prevalence of infection (4%) among tick-borne diseases, while both Lyme disease and Severe fever with thrombocytopenia syndrome had a prevalence of 2%. The average rate of tick bites among respondents' pets was 14%, with bites predominantly located on the ears, back, and abdomen. The strongest correlation was observed between tick bite rate and subsequent infections, emphasizing its role as the primary contributing factors to infectious status. Moreover, our results indicated that the causal structure of tick-borne disease infections varied across different cities, underscoring the significance of considering the ecological environment and regional knowledge on ticks. This study provides valuable insights into the current landscape of tick-borne disease infections in northeast China and identifies potential behavioral and cognitive factors, an aspect that has not been previously investigated. Our findings enable predictions on the future impact of knowledge dissemination efforts and improved urban facilities on mitigating tick bites and reducing tick-borne disease infections.

2.
Vaccine ; 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38797627

RESUMEN

BACKGROUND: We recently reported a near disappearance of B. pertussis and a decline in anti-B. pertussis antibodies during the peak implementation of Coronavirus disease 2019 (COVID-19) non-pharmaceutical interventions (NPI) in 2021 in British Columbia (BC), Canada. During 2021-2023, incidence of reported B. pertussis cases remained low in BC at < 1/100,000 population. This study determined how serological evidence of B. pertussis changed after the gradual relaxation of NPI between 2021-2023. METHODS: Randomly selected blood samples from school staff 25-51 years old (n = 65) were collected yearly between 2021-2023 in the Vancouver metropolitan area, BC, Canada, and tested for anti-pertussis toxin (PT) IgG levels. Serological evidence of B. pertussis infection (thereafter "seroconversion") was defined as a quantifiable anti-PT IgG levels in subjects with anti-PT IgG levels below lower limit of quantification in the preceding year or a > 4-fold increase in anti-PT IgG levels between two subsequent years. Samples were also tested for anti-diphtheria toxoid (DT) IgG, and similar seroconversion criteria were applied to exclude seroconversion due to vaccination with tetanus-diphtheria-acellular-pertussis (Tdap). RESULTS: Three subjects met seroconversion criteria for anti-PT IgG between 2021 and 2022 and 9 between 2022 and 2023, yielding a seroconversion rate of 4.6 /100 person-years and 14.9/100 person-years, P = 0.127, respectively. None of the subjects met the criteria for vaccination with Tdap. The geometric mean concentration of anti-PT IgG showed a statistically significant decrease in 2022 compared with 2021, 4.8 IU/mL IU/ml (95 % confidence interval [CI], 3.8-5.9) vs. 6.4 IU/ml (95 % CI, 4.9-8.2; p = 0.001), followed by a statistically significant increase in 2023 compared with 2022 6.5 IU/ml (95 % CI, 4.9-8.5) vs. 4.8 IU/ml (95 % CI, 3.8-5.9; p = 0.0006), respectively. DISCUSSION: Serological evidence of B. pertussis increased between 2022 and 2023 despite low reported cases, which suggests that B. pertussis circulation resumed after relaxing of COVID-19 NPI.

3.
MAGMA ; 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578520

RESUMEN

OBJECTIVE: To assess the performance of hybrid multi-dimensional magnetic resonance imaging (HM-MRI) in quantifying hematoxylin and eosin (H&E) staining results, grading and predicting isocitrate dehydrogenase (IDH) mutation status of gliomas. MATERIALS AND METHODS: Included were 71 glioma patients (mean age, 50.17 ± 13.38 years; 35 men). HM-MRI images were collected at five different echo times (80-200 ms) with seven b-values (0-3000 s/mm2). A modified three-compartment model with very-slow, slow and fast diffusion components was applied to calculate HM-MRI metrics, including fractions, diffusion coefficients and T2 values of each component. Pearson correlation analysis was performed between HM-MRI derived fractions and H&E staining derived percentages. HM-MRI metrics were compared between high-grade and low-grade gliomas, and between IDH-wild and IDH-mutant gliomas. Using receiver operational characteristic (ROC) analysis, the diagnostic performance of HM-MRI in grading and genotyping was compared with mono-exponential models. RESULTS: HM-MRI metrics FDvery-slow and FDslow demonstrated a significant correlation with the H&E staining results (p < .05). Besides, FDvery-slow showed the highest area under ROC curve (AUC = 0.854) for grading, while Dslow showed the highest AUC (0.845) for genotyping. Furthermore, a combination of HM-MRI metrics FDvery-slow and T2Dslow improved the diagnostic performance for grading (AUC = 0.876). DISCUSSION: HM-MRI can aid in non-invasive diagnosis of gliomas.

4.
Nat Nanotechnol ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38480836

RESUMEN

The efficacy of STING (stimulator of interferon genes) agonists is due to various factors, primarily inefficient intracellular delivery, low/lack of endogenous STING expression in many tumours, and a complex balance between tumour control and progression. Here we report a universal STING mimic (uniSTING) based on a polymeric architecture. UniSTING activates STING signalling in a range of mouse and human cell types, independent of endogenous STING expression, and selectively stimulates tumour control IRF3/IFN-I pathways, but not tumour progression NF-κB pathways. Intratumoural or systemic injection of uniSTING-mRNA via lipid nanoparticles (LNPs) results in potent antitumour efficacy across established and advanced metastatic tumour models, including triple-negative breast cancer, lung cancer, melanoma and orthotopic/metastatic liver malignancies. Furthermore, uniSTING displays an effective antitumour response superior to 2'3'-cGAMP and ADU-S100. By favouring IRF3/IFN-I activity over the proinflammatory NF-κB signalling pathway, uniSTING promotes dendritic cell maturation and antigen-specific CD8+ T-cell responses. Extracellular vesicles released from uniSTING-treated tumour cells further sensitize dendritic cells via exosome-containing miRNAs that reduced the immunosuppressive Wnt2b, and a combination of LNP-uniSTING-mRNA with α-Wnt2b antibodies synergistically inhibits tumour growth and prolongs animal survival. Collectively, these results demonstrate the LNP-mediated delivery of uniSTING-mRNA as a strategy to overcome the current STING therapeutic barriers, particularly for the treatment of multiple cancer types in which STING is downregulated or absent.

5.
J Exp Bot ; 75(11): 3500-3520, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38517318

RESUMEN

Verticillium wilt, a soilborne vascular disease caused by Verticillium dahliae, strongly affects cotton yield and quality. In this study, an isolated rhizosphere bacterium, designated Bacillus velezensis BvZ45-1, exhibited >46% biocontrol efficacy against cotton verticillium wilt under greenhouse and field conditions. Moreover, through crude protein extraction and mass spectrometry analyses, we found many antifungal compounds present in the crude protein extract of BvZ45-1. The purified oxalate decarboxylase Odx_S12 from BvZ45-1 inhibited the growth of V. dahliae Vd080 by reducing the spore yield, causing mycelia to rupture, spore morphology changes, cell membrane rupture, and cell death. Subsequently, overexpression of Odx_S12 in Arabidopsis significantly improved plant resistance to V. dahliae. Through studies of the resistance mechanism of Odx_S12, V. dahliae was shown to produce oxalic acid (OA), which has a toxic effect on Arabidopsis leaves. Odx_S12 overexpression reduced Arabidopsis OA content, enhanced tolerance to OA, and improved resistance to verticillium wilt. Transcriptomics and quantitative real-time PCR analysis revealed that Odx_S12 promoted a reactive oxygen species burst and a salicylic acid- and abscisic acid-mediated defence response in Arabidopsis. In summary, this study not only identified B. velezensis BvZ45-1 as an efficient biological control agent, but also identified the resistance gene Odx_S12 as a candidate for cotton breeding against verticillium wilt.


Asunto(s)
Arabidopsis , Ascomicetos , Bacillus , Carboxiliasas , Gossypium , Enfermedades de las Plantas , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Bacillus/fisiología , Gossypium/genética , Gossypium/microbiología , Gossypium/metabolismo , Carboxiliasas/metabolismo , Carboxiliasas/genética , Arabidopsis/genética , Arabidopsis/microbiología , Arabidopsis/metabolismo , Arabidopsis/inmunología , Ascomicetos/fisiología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Resistencia a la Enfermedad/genética , Verticillium/fisiología
6.
PLoS Pathog ; 20(1): e1011823, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38236820

RESUMEN

A variety of coordinated host-cell responses are activated as defense mechanisms against pore-forming toxins (PFTs). Bacillus thuringiensis (Bt) is a worldwide used biopesticide whose efficacy and precise application methods limits its use to replace synthetic pesticides in agricultural settings. Here, we analyzed the intestinal defense mechanisms of two lepidopteran insect pests after intoxication with sublethal dose of Bt PFTs to find out potential functional genes. We show that larval intestinal epithelium was initially damaged by the PFTs and that larval survival was observed after intestinal epithelium regeneration. Further analyses showed that the intestinal regeneration caused by Cry9A protein is regulated through c-Jun NH (2) terminal kinase (JNK) and Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. JAK/STAT signaling regulates intestinal regeneration through proliferation and differentiation of intestinal stem cells to defend three different Bt proteins including Cry9A, Cry1F or Vip3A in both insect pests, Chilo suppressalis and Spodoptera frugiperda. Consequently, a nano-biopesticide was designed to improve pesticidal efficacy based on the combination of Stat double stranded RNA (dsRNA)-nanoparticles and Bt strain. This formulation controlled insect pests with better effect suggesting its potential use to reduce the use of synthetic pesticides in agricultural settings for pest control.


Asunto(s)
Bacillus thuringiensis , Plaguicidas , Animales , Bacillus thuringiensis/genética , Quinasas Janus/genética , Tirosina , Endotoxinas/genética , Insectos , Spodoptera/genética , Larva , Plaguicidas/farmacología , Regeneración , Proteínas Bacterianas/farmacología , Proteínas Bacterianas/genética , Proteínas Hemolisinas/farmacología , Proteínas Hemolisinas/genética , Plantas Modificadas Genéticamente , Control Biológico de Vectores/métodos
7.
Sheng Wu Gong Cheng Xue Bao ; 40(1): 81-93, 2024 Jan 25.
Artículo en Chino | MEDLINE | ID: mdl-38258633

RESUMEN

The chloroplast genome encodes many key proteins involved in photosynthesis and other metabolic processes, and metabolites synthesized in chloroplasts are essential for normal plant growth and development. Root-UVB (ultraviolet radiation B)-sensitive (RUS) family proteins composed of highly conserved DUF647 domain belong to chloroplast proteins. They play an important role in the regulation of various life activities such as plant morphogenesis, material transport and energy metabolism. This article summarizes the recent advances of the RUS family proteins in the growth and development of plants such as embryonic development, photomorphological construction, VB6 homeostasis, auxin transport and anther development, with the aim to facilitate further study of its molecular regulation mechanism in plant growth and development.


Asunto(s)
Cloroplastos , Rayos Ultravioleta , Femenino , Embarazo , Humanos , Transporte Biológico , Cloroplastos/genética , Desarrollo Embrionario , Desarrollo de la Planta/genética
8.
Proc Natl Acad Sci U S A ; 120(50): e2122178120, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38051771

RESUMEN

Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to be developed. Our previous study showed the synthetic TLR2/TLR6 ligand fibroblast stimulating lipopeptide (FSL-1) prolonged survival and provided MyD88-dependent mitigation of hematopoietic acute radiation syndrome (H-ARS) in mice. Although mice and humans differ in TLR number, expression, and function, nonhuman primate (NHP) TLRs are like those of humans; therefore, studying both animal models is critical for drug development. The objectives of this study were to determine the efficacy of FSL-1 on hematopoietic recovery in small and large animal models subjected to sublethal total body irradiation and investigate its mechanism of action. In mice, we demonstrate a lack of adverse effects, an easy route of delivery (subcutaneous) and efficacy in promoting hematopoietic progenitor cell proliferation by FSL-1. NHP given radiation, followed a day later with a single subcutaneous administration of FSL-1, displayed no adversity but showed elevated hematopoietic cells. Our analyses revealed that FSL-1 promoted red blood cell development and induced soluble effectors following radiation exposure. Cytologic analysis of bone marrow aspirates revealed a striking enhancement of mononuclear progenitor cells in FSL-1-treated NHP. Combining the efficacy of FSL-1 in promoting hematopoietic cell recovery with the lack of adverse effects induced by a single administration supports the application of FSL-1 as a viable countermeasure against H-ARS.


Asunto(s)
Síndrome de Radiación Aguda , Receptor Toll-Like 2 , Humanos , Ratones , Animales , Receptor Toll-Like 6 , Ligandos , Síndrome de Radiación Aguda/tratamiento farmacológico , Primates , Fibroblastos
10.
React Chem Eng ; 8(9): 2223-2233, 2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-38014416

RESUMEN

A novel plate-to-plate dielectric barrier discharge microreactor (micro DBD) has been demonstrated in CO2 splitting. In this design, the ground electrode has a cooling microchannel to maintain the electrode temperature in the 263-298 K range during plasma operation. A small gap size between the electrodes of 0.50 mm allowed efficient heat transfer from the surrounding plasma to the ground electrode surface to compensate for heat released in the reaction zone and maintain a constant temperature. The effect of temperature on CO2 conversion and energy efficiency was studied at a voltage of 6-9 kV, a frequency of 60 kHz and a constant CO2 flow rate of 20 ml min-1. The CO2 decomposition rate first increased and then decreased as the electrode temperature decreased from 298 to 263 K with a maximum rate observed at 273 K. Operation at lower temperatures enhanced the vibrational dissociation of the CO2 molecule as opposed to electronic excitation which is the main mechanism at room temperature in conventional DBD reactors, however it also reduced the rate of elementary reaction steps. The counterplay between these two effects leads to a maximum in the reaction rate. The power consumption monotonously increased as the temperature decreased. The effective capacitance of the reactor increased by 1.5 times at 263 K as compared to that at 298 K changing the electric field distribution inside the plasma zone.

11.
ACS Sustain Chem Eng ; 11(34): 12821-12832, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37654788

RESUMEN

A two-dimensional gliding arc reactor for NOx synthesis was investigated in this study using AC pulsed mode operation. Tests with a duty cycle of 40 or 60% achieved the lowest energy consumption of 6.95 MJ/mol, which is an improvement of 15% from the case of continuous operation. Based on the results achieved, a new method for analyzing the spatial profile of the reactor was presented. The reactor was divided into five zones along the arc propagation, and results indicated that the first zone and last zone of the gliding arc reactor had higher energy consumption (9.59 and 8.63 MJ/mol, respectively), while lower consumption was observed in the middle parts of the reactor with a minimum of 5.00 MJ/mol. Spatial-resolved optical emission spectra, the deduced electron density, and temperature indicated the nonuniformity in plasma properties, which corresponds to the NOx production performance across the reactor. This research provides information and discussion that can be used for understanding and optimization of gliding arc reactors toward efficient nitrogen fixation.

12.
Brain Imaging Behav ; 17(5): 530-540, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37433970

RESUMEN

OBJECTIVES: The alterations in cerebellar activity that occur in vascular mild cognitive impairment remain largely unexplored. This study aimed to investigate potential associations between abnormal cerebellar functional connectivity (FC) and changes in cognitive function by examining intracerebellar and cerebellar-cerebral FC. METHODS: MRI data were collected from seventy-two patients with vascular mild cognitive impairment (VMCI), comprising 38 patients with small vessel mild cognitive impairment (SVMCI) and 34 with poststroke mild cognitive impairment (PSMCI), and from 43 demographically matched healthy controls (HCs). Changes in FC between subregions within the cerebellum and from each cerebellar subregion to the selected cerebral seed points in VMCI patients were calculated, and the association of these changes with cognitive function was examined. RESULTS: Compared with HCs, we found that VMCI patients had 11 cerebellar subregions showing significant differences (mainly decreases) in FC with brain regions in the default-mode network (DMN), sensory-motor network (SMN), and frontoparietal network (FPN). In the intracerebellar FC analysis, 47 (8%) cerebellar connections had significant intergroup differences, mainly a reduced magnitude of FC in VMCI patients. In the correlation analysis, higher Montreal Cognitive Assessment (MoCA) scores were correlated with stronger intracerebellar FC (left crus II-right lobule VI, left crus II-right lobule VIIb) and cerebellar-cerebral FC (right lobule X-left precuneus, vermal lobule IX-right inferior parietal lobule) in both the SVMCI and PSMCI groups. CONCLUSION: These findings suggest prominent intracerebellar and cerebellar-cerebral FC abnormalities in VMCI patients, contributing evidence for a possible role of the cerebellum in cognitive processes.


Asunto(s)
Disfunción Cognitiva , Imagen por Resonancia Magnética , Humanos , Cerebelo/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Lóbulo Parietal , Disfunción Cognitiva/diagnóstico por imagen
13.
Mol Immunol ; 160: 121-132, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37429063

RESUMEN

Our previous research demonstrated that the tetraspan MS4A6D is an adapter of VSIG4 that controls NLRP3 inflammasome activation (Sci Adv. 2019: eaau7426); however, the expression, distribution and biofunction of MS4A6D are still poorly understood. Here, we showed that MS4A6D is restricted to mononuclear phagocytes and that its gene transcript is controlled by the transcription factor NK2 homeobox-1 (NKX2-1). Ms4a6d-deficient (Ms4a6d-/-) mice showed normal macrophage development but manifested a greater survival advantage against endotoxin (lipopolysaccharide) challenge. Mechanistically, MS4A6D homodimers crosslinked with MHC class II antigen (MHC-II) to form a surface signaling complex under acute inflammatory conditions. MHC-II occupancy triggered Tyr241 phosphorylation in MS4A6D, leading to activation of SYK-CREB signaling cascades, further resulting in augmenting the transcription of proinflammatory genes (Il1b, Il6 and Tnfa) and amplifying the secretion of mitochondrial reactive oxygen species (mtROS). Deletion of Tyr241 or interruption of Cys237-mediated MS4A6D homodimerization in macrophages alleviated inflammation. Importantly, both Ms4a6dC237G and Ms4a6dY241G mutation mice phenocopied Ms4a6d-/- animals to prevent endotoxin lethality, highlighting MS4A6D as a novel target for treating macrophage-associated disorders.


Asunto(s)
Antígenos de Histocompatibilidad Clase II , Macrófagos , Proteínas de la Membrana , Animales , Ratones , Endotoxinas/metabolismo , Inflamación/metabolismo , Lipopolisacáridos/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Proteínas de la Membrana/metabolismo
14.
Acta Biochim Biophys Sin (Shanghai) ; 55(9): 1456-1466, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37491880

RESUMEN

Homocysteine (Hcy) is a risk factor for multiple chronic diseases, and vascular endothelial cell injury has been regarded as the initiating step for this process. miRNAs are involved in Hcy-induced endothelial dysfunction, while the underlying mechanism and roles of miRNAs in pulmonary endothelial dysfunction induced by homocysteine are unknown. Here, we find that miR-205-5p alleviates pulmonary endothelial dysfunction by targeting FOXO1 in CBS +/‒ mice to protect against Hcy-induced pulmonary endothelial dysfunction. Mechanistically, we show that Hcy can lead to DNA hypermethylation of the miR-205-5p promoter due to the increased binding of DNMT1 to its promoter, which contributes to reduction of miR-205-5p expression. In summary, miR-205-5p promoter hypermethylation causes downregulation of miR-205-5p expression, resulting in a reduction in miR-205-5p binding to FOXO1 during homocysteine-induced pulmonary endothelial dysfunction. Our data indicate that miR-205-5p may be a potential therapeutic target against Hcy-induced pulmonary injury.


Asunto(s)
MicroARNs , Animales , Ratones , Metilación de ADN , Regulación hacia Abajo , Células Endoteliales/metabolismo , Endotelio/metabolismo , MicroARNs/genética , MicroARNs/metabolismo
15.
Front Aging Neurosci ; 15: 1224525, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37416325

RESUMEN

Background and objective: This study aims to examine the role of neurovascular coupling (NVC) in vascular cognitive impairment (VCI) by investigating the relationship between white matter lesion (WML) burden, NVC, and cognitive deficits. Additionally, we aim to explore the potential of NVC as a tool for understanding the neural mechanisms underlying VCI. Methods: This study included thirty-eight small vessel disease cognitive impairment (SVCI) patients, 34 post-stroke cognitive impairment (PSCI) patients, and 43 healthy controls (HC). Comprehensive assessments, including neuroimaging and neuropsychological testing, were conducted to evaluate cognitive function. WML burden was measured and correlated with NVC coefficients to examine the relationship between white matter pathology and NVC. Mediation analysis was employed to explore the link relationship between NVC, WML burden, and cognitive function. Results: The present study showed that NVC was significantly reduced in the SVCI and PSCI groups compared with HCs at both whole-brain and brain region level. The analysis revealed notable findings regarding NVC in relation to WML burden and cognitive function in VCI patients. Specifically, reduced NVC coefficients were observed within higher order brain systems responsible for cognitive control and emotion regulation. Mediation analysis demonstrated that NVC played a mediating role in the relationship between WML burden and cognitive impairment. Conclusion: This study reveals the mediating role of NVC in the relationship between WML burden and cognitive function in VCI patients. The results demonstrate the potential of the NVC as an accurate measure of cognitive impairment and its ability to identify specific neural circuits affected by WML burden.

16.
ACS Appl Mater Interfaces ; 15(30): 36759-36770, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37477654

RESUMEN

The development of degradable, cost-effective, and eco-friendly ionic conductive gels is highly required to reduce electronic waste originating from flexible electronic devices. However, biocompatible, degradable, tough, and durable conductive gels are challenging to achieve. Herein, we develop a facile strategy for the design and synthesis of degradable tough eutectogels by integrating an electrostatically driven supramolecular network composed of branched polyacrylic acid (PAA) and monoethanolamine (MEA) into a green deep eutectic solvent with chitosan quaternary ammonium salt (CQS). The specially designed PAA/MEA/CQS eutectogels present multiple desired properties, including high transparency, widely adjustable mechanical properties, high resilience, reliable adhesiveness, excellent self-healing ability, good conductivity, remarkable anti-freezing performance, and antibacterial properties. The dynamic and reversible supramolecular interactions not only significantly enhance the mechanical properties of the PAA/MEA/CQS eutectogels but also enable fast degradation, addressing the dilemma between mechanical strength and degradability. More importantly, a biocompatible and degradable multifunctional ionic skin is successfully fabricated based on the PAA/MEA/CQS eutectogel, exhibiting high sensitivity, a wide sensing range, and a rapid response speed toward strain, pressure, and temperature. Thus, this study offers a promising strategy for fabricating degradable tough eutectogels, which show great potential as high-performance ionic skins for next-generation flexible wearable electronic devices.


Asunto(s)
Piel , Iones/química , Piel/química , Antibacterianos/química , Cicatrización de Heridas , Adhesividad , Geles/química , Materiales Biocompatibles/química , Humanos
17.
Cell Metab ; 35(8): 1390-1405.e8, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37343564

RESUMEN

Inflammation is closely associated with obesity and related metabolic disorders. However, its origin during obesity is largely unknown. Here, we report that ubiquitin-conjugating enzyme E2M (UBE2M) is critical to obesity-related inflammation induced by macrophages. In mice with UBE2M-deficient macrophages, obesity, insulin resistance, and hepatic steatosis induced by a high-fat diet are greatly alleviated, an effect related to the decreased proinflammatory activity of macrophages due to reduced IL-1ß production. Mechanistically, UBE2M deficiency inhibits the neddylation of E3 ubiquitin ligase TRIM21 on K129/134, leading to reduced recruitment and ubiquitination-mediated degradation of E3 ubiquitin ligase VHL. Subsequently, VHL reduces HIF-1α-induced IL-1ß production by degrading HIF-1α. Targeting macrophage TRIM21 with Trim21 antisense oligonucleotide-loaded red blood cell extracellular vesicles effectively inhibits obesity-induced inflammation and related metabolic disorders. Thus, our results demonstrate that macrophage UBE2M is essential for obesity-induced inflammation and that TRIM21 is a proof-of-concept target for treating obesity and associated metabolic diseases.


Asunto(s)
Enfermedades Metabólicas , Ubiquitina-Proteína Ligasas , Ratones , Animales , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Obesidad/complicaciones , Obesidad/metabolismo , Inflamación , Enfermedades Metabólicas/etiología
18.
PLoS Pathog ; 19(6): e1011482, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37379353

RESUMEN

Wall teichoic acid (WTA) is the abundant cell wall-associated glycopolymer in Gram-positive bacteria, playing crucial roles in surface proteins retention, bacterial homeostasis, and virulence. The WTA glycosylation of Listeria monocytogenes is essential for surface anchoring of virulence factors, whereas the nature and function of the noncovalent interactions between cell wall-associated proteins and WTA are less unknown. In this study, we found that galactosylated WTA (Gal-WTA) of serovar (SV) 4h L. monocytogenes plays a key role in modulating the novel glycine-tryptophan (GW) domain-containing autolysin protein LygA through direct interactions. Gal-deficient WTA of Lm XYSN (ΔgalT) showed a dramatic reduction of LygA on the cell surface. We demonstrated that LygA binds to Gal-WTA through the GW domains, and the binding affinity is associated with the number of GW motifs. Moreover, we confirmed the direct Gal-dependent binding of the GW protein Auto from the type I WTA strain, which has no interaction with rhamnosylated WTA, indicating that the complexity of both WTA and GW proteins affect the coordination patterns. Importantly, we revealed the crucial roles of LygA in facilitating bacterial homeostasis as well as crossing the intestinal and blood-brain barriers. Altogether, our findings suggest that both the glycosylation patterns of WTA and a fixed numbers of GW domains are closely associated with the retention of LygA on the cell surface, which promotes the pathogenesis of L. monocytogenes within the host.


Asunto(s)
Listeria monocytogenes , Virulencia , Membrana Celular/metabolismo , Pared Celular/metabolismo , Factores de Virulencia/metabolismo , Proteínas de la Membrana/metabolismo , Ácidos Teicoicos/metabolismo , Proteínas Bacterianas/metabolismo
19.
React Chem Eng ; 8(5): 1125-1133, 2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-37152402

RESUMEN

Non-oxidative methane coupling in an atmospheric pressure plasma jet reactor with an internal diameter of 3.0 mm has been studied. The jet reactor consisted of a quartz tube surrounded by a copper ring and a stainless-steel tube, which were separated by a variable distance. The stainless-steel tube (inner diameter: 1.0 mm, outer diameter: 1.5 mm) served as high voltage electrode and gas inlet. The jet characteristics with different tip angles of the high voltage electrode were investigated using voltage-current waveforms and gas analysis at a constant methane flow rate of 100 ml min-1. The effect of the length of the ground electrode and the gap between the electrodes on conversion, C2 selectivity and energy efficiency has been studied. The methane conversion was nearly tripled with a sharp angle of the electrode (15°), while the energy consumption was reduced from 150 to 55 kJ molC2H y -1. The carbon deposition was also reduced.

20.
Cell ; 186(11): 2288-2312, 2023 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-37236155

RESUMEN

Inflammasomes are critical sentinels of the innate immune system that respond to threats to the host through recognition of distinct molecules, known as pathogen- or damage-associated molecular patterns (PAMPs/DAMPs), or disruptions of cellular homeostasis, referred to as homeostasis-altering molecular processes (HAMPs) or effector-triggered immunity (ETI). Several distinct proteins nucleate inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRC4/NAIP, AIM2, pyrin, and caspases-4/-5/-11. This diverse array of sensors strengthens the inflammasome response through redundancy and plasticity. Here, we present an overview of these pathways, outlining the mechanisms of inflammasome formation, subcellular regulation, and pyroptosis, and discuss the wide-reaching effects of inflammasomes in human disease.


Asunto(s)
Inflamasomas , Humanos , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Adaptadoras de Señalización CARD/metabolismo , Caspasas/metabolismo , Muerte Celular , Inflamasomas/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis
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