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1.
Vet Microbiol ; 297: 110202, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39094384

RESUMO

Herpesviruses-encoded microRNAs (miRNAs) have been discovered to be essential regulators in viral life cycle, participating in viral replication, latent or lytic infection, and immunological escape. However, the roles of miRNAs encoded by duck plague virus (DPV) are still unknown. Dev-miR-D28-3p is a miRNA uniquely encoded by DPV CHv strain. The aim of this study was to explore the effect of dev-miR-D28-3p on DPV replication and explore the potential mechanisms involved. Our findings demonstrated that transfection of dev-miR-D28-3p mimic into duck embryo fibroblasts (DEFs) effectively suppressed viral copies, viral titers and viral protein expressions during DPV infection, while the results above were reversed after transfection with dev-miR-D28-3p inhibitor. Subsequently, we further discovered that dev-miR-D28-3p specifically bound to DPV-encoded UL27 and inhibited its expression, suggesting that UL27 was the target gene of dev-miR-D28-3p. Finally, we investigated the role of UL27 in DPV replication and found the overexpression of UL27 increased viral copies, viral titers, and viral protein expressions; whereas the opposite results appear when knockdown of UL27. Our findings illustrated a novel mechanism that DPV regulated itself replication via dev-miR-D28-3p, paving the way for exploring the role of DPV-encoded miRNAs.

2.
Proc Natl Acad Sci U S A ; 121(34): e2405632121, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39150783

RESUMO

Transcription of eukaryotic protein-coding genes generates immature mRNAs that are subjected to a series of processing events, including capping, splicing, cleavage, and polyadenylation (CPA), and chemical modifications of bases. Alternative polyadenylation (APA) greatly contributes to mRNA diversity in the cell. By determining the length of the 3' untranslated region, APA generates transcripts with different regulatory elements, such as miRNA and RBP binding sites, which can influence mRNA stability, turnover, and translation. In the model plant Arabidopsis thaliana, APA is involved in the control of seed dormancy and flowering. In view of the physiological importance of APA in plants, we decided to investigate the effects of light/dark conditions and compare the underlying mechanisms to those elucidated for alternative splicing (AS). We found that light controls APA in approximately 30% of Arabidopsis genes. Similar to AS, the effect of light on APA requires functional chloroplasts, is not affected in mutants of the phytochrome and cryptochrome photoreceptor pathways, and is observed in roots only when the communication with the photosynthetic tissues is not interrupted. Furthermore, mitochondrial and TOR kinase activities are necessary for the effect of light. However, unlike AS, coupling with transcriptional elongation does not seem to be involved since light-dependent APA regulation is neither abolished in mutants of the TFIIS transcript elongation factor nor universally affected by chromatin relaxation caused by histone deacetylase inhibition. Instead, regulation seems to correlate with changes in the abundance of constitutive CPA factors, also mediated by the chloroplast.


Assuntos
Arabidopsis , Cloroplastos , Regulação da Expressão Gênica de Plantas , Luz , Poliadenilação , Arabidopsis/genética , Arabidopsis/metabolismo , Cloroplastos/metabolismo , Cloroplastos/genética , Processamento Alternativo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
3.
Heliyon ; 10(14): e34568, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39114020

RESUMO

Malignant urban gas accidents, accounting for only approximately 1 % of the total gas accidents in China, are responsible for over 50 % of fatalities, thus becoming a major cause of public concern regarding gas safety. A comprehensive understanding of the characteristics of historical accidents is an effective way to prevent and reduce future accidents. In this regard, the study meticulously collects and analyzes all malignant gas accidents that occurred in China from 2013 to 2022. This approach can effectively clarify the focus of gas accident prevention, and also facilitate the implementation of more targeted preventive measures. The study provides diverse perspectives and comprehensive statistics on accidents using 10 variables in 6 dimensions: time (year, month, day, hour), location (province, place), gas source, type, cause, and level. In addition to common quantitative statistics, proportional analyses and visual displays, methods such as contingency tables, t-tests, chi-square tests, and cluster analyses were also used to provide more in-depth analyses and identify more potential patterns. The findings elucidate that: (1) Over the past decade, the yearly distribution of malignant gas accidents in China has been relatively stable; but, individual, particularly major accidents, have significantly influenced the overall severity; (2) June and July are the peak months for such accidents; (3) The most severe accidents occur during 6:00-6:59 a.m., 11:00-11:59 a.m., and 11:00-11:59 p.m.; (4) Central and eastern provinces are the epicenters of malignant gas accidents; (5) Residential accommodations, and restaurants and shops are frequently affected; (6) Liquefied petroleum gas, despite comprising merely 8.7 % of the aggregate supply, is implicated in over half of the malignant occurrences and associated fatalities; (7) Explosions account for approximately 78.49 % of these accidents; (8) Among the accident causes, violations of rules by workers stands as the foremost contributor; (9) Malignant gas accidents are generally larger accident. Moreover, this manuscript delves into the underlying reasons behind each noteworthy statistical trend and analyzes the critical issues facing the gas industry. This investigation not only bridges the gap in the statistical profiling of malignant gas accidents within China but also furnishes invaluable insights that may guide preventive measures against urban gas-related disasters. Furthermore, the methodological approaches and variable selections explored in this study lay a robust foundation for future endeavors in the realm of malignant gas accident management research and practice.

4.
Biomater Adv ; 164: 213990, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39154560

RESUMO

Microbial keratitis associated with contact lenses (CLs) wear remains a significant clinical concern. Antibiotic therapy is the current standard of care. However, the emergence of multidrug-resistant pathogens necessitates the investigation of alternative strategies. Antibiotic-free antimicrobial contact lenses (AFAMCLs) represent a promising approach in this regard. The effectiveness of CLs constructed with a variety of antibiotic-free antimicrobial strategies against microorganisms has been demonstrated. However, the impact of these antimicrobial strategies on CLs biocompatibility remains unclear. In the design and development of AFAMCLs, striking a balance between robust antimicrobial performance and optimal biocompatibility, including safety and wearing comfort, is a key issue. This review provides a comprehensive overview of recent advancements in AFAMCLs technology. The focus is on the antimicrobial efficacy and safety of various strategies employed in AFAMCLs construction. Furthermore, this review investigates the potential impact of these strategies on CLs parameters related to wearer comfort. This review aims to contribute to the continuous improvement of AFAMCLs and provide a reference for the trade-off between resistance to microorganisms and wearing comfort. In addition, it is hoped that this review can also provide a reference for the antimicrobial design of other medical devices.

5.
Mol Cell ; 84(15): 2804-2806, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39121842

RESUMO

In a recent publication in Cell, Kowalski et al.1 developed an interdisciplinary and multiplexed approach to uncover regulatory modules of alternative polyadenylation, involving single-cell-based gene perturbation, isoform abundance analysis, machine learning of RNA motifs, and massively parallel reporter assays.


Assuntos
Poliadenilação , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Aprendizado de Máquina , Análise de Célula Única , Animais
6.
World J Diabetes ; 15(7): 1537-1550, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39099805

RESUMO

BACKGROUND: Dysfunction of the glymphatic system in the brain in different stages of altered glucose metabolism and its influencing factors are not well characterized. AIM: To investigate the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states, the present study employed diffusion tensor imaging along the perivascular space (DTI-ALPS) index. METHODS: Sample size was calculated using the pwr package in R software. This cross-sectional study enrolled 22 patients with normal glucose metabolism (NGM), 20 patients with prediabetes, and 22 patients with type 2 diabetes mellitus (T2DM). A 3.0T magnetic resonance imaging was used to evaluate the function of the glymphatic system. The mini-mental state examination (MMSE) was used to assess general cognitive function. The DTI-ALPS index of bilateral basal ganglia and the mean DTI-ALPS index was calculated. Further, the correlation between DTI-ALPS and clinical features was assessed. RESULTS: The left-side, right-side, and mean DTI-ALPS index in the T2DM group were significantly lower than that in the NGM group. The right-side DTI-ALPS and mean DTI-ALPS index in the T2DM group were significantly lower than those in the prediabetes group. DTI-ALPS index lateralization was not observed. The MMSE score in the T2DM group was significantly lower than that in the NGM and prediabetes group. After controlling for sex, the left-side DTI-ALPS and mean DTI-ALPS index in the prediabetes group were positively correlated with 2-hour postprandial blood glucose level; the left-side DTI-ALPS index was negatively correlated with total cholesterol and low-density lipoprotein level. The right-side DTI-ALPS and mean DTI-ALPS index were negatively correlated with the glycosylated hemoglobin level and waist-to-hip ratio in the prediabetes group. The left-side, right-side, and mean DTI-ALPS index in the T2DM group were positively correlated with height. The left-side and mean DTI-ALPS index in the T2DM group were negatively correlated with high-density lipoprotein levels. CONCLUSION: Cerebral glymphatic system dysfunction may mainly occur in the T2DM stage. Various clinical variables were found to affect the DTI-ALPS index in different glucose metabolism states. This study enhances our understanding of the pathophysiology of diabetic brain damage and provides some potential biological evidence for its early diagnosis.

7.
Small ; : e2402609, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075935

RESUMO

NiSe is a promising electrode material for enhancing the energy density of supercapacitors, but it faces challenges such as sensitivity to electrolyte anions, limited specific capacity, and unstable cycling. This study employs a strategy of metal atom doping to address these issues. Through a hydrothermal reaction, Mo-doped NiSe demonstrates significant improvement in electrochemical performance, exhibiting high capacity (799.90 C g-1), splendid rate performance, and excellent cyclic stability (90% capacity retention). The introduction of Mo induces charge redistribution in NiSe, leading to a reduction in the band gap. Theoretical calculation reveals that Mo doping can effectively enhance the electrical conductivity and the adsorption energy of NiSe. A flexible printed hybrid Mo-doped NiSe-based supercapacitor is fabricated, demonstrating superior electrochemical performance (367.04 mF cm-2) and the ability to power timers, LEDs, and toy fans. This research not only deepens the understanding of the electrochemical properties of metal-doped NiSe but also highlights its application potential in high-performance supercapacitors.

8.
J Hepatol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38992769

RESUMO

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

9.
Front Microbiol ; 15: 1431672, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015737

RESUMO

Alphaherpesvirus is a widespread pathogen that causes diverse diseases in humans and animals and can severely damage host health. Alphaherpesvirus particles comprise a DNA core, capsid, tegument and envelope; the tegument is located between the nuclear capsid and envelope. According to biochemical and proteomic analyses of alphaherpesvirus particles, the tegument contains at least 24 viral proteins and plays an important role in the alphaherpesvirus life cycle. This article reviews the important role of tegument proteins and their interactions during the viral life cycle to provide a reference and inspiration for understanding alphaherpesvirus infection pathogenesis and identifying new antiviral strategies.

10.
J Adv Res ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033876

RESUMO

INTRODUCTION: Environmental and occupational exposure to cadmium (Cd) has been shown to cause acute kidney injury (AKI). Previous studies have demonstrated that autophagy inhibition and lysosomal dysfunction are important mechanisms of Cd-induced AKI. OBJECTIVES: Transcription factor EB (TFEB) is a critical transcription regulator that modulates autophagy-lysosome function, but its role in Cd-induced AKI is yet to be elucidated. Thus, in vivo and in vitro studies were conducted to clarify this issue. METHODS AND RESULTS: Data firstly showed that reduced TFEB expression and nuclear translocation were evident in Cd-induced AKI models, accompanied by autophagy-lysosome dysfunction. Pharmacological and genetic activation of TFEB improved Cd-induced AKI via alleviating autophagy inhibition and lysosomal dysfunction, whereas Tfeb knockdown further aggravated this phenomenon, suggesting the key role of TFEB in Cd-induced AKI by regulating autophagy. Mechanistically, Cd activated mechanistic target of rapamycin complex 1 (mTORC1) to enhance TFEB phosphorylation and thereby inhibiting TFEB nuclear translocation. Cd also activated chromosome region maintenance 1 (CRM1) to promote TFEB nuclear export. Meanwhile, Cd activated general control non-repressed protein 5 (GCN5) to enhance nuclear TFEB acetylation, resulting in the decreased TFEB transcriptional activity. Moreover, inhibition of CRM1 or GCN5 alleviated Cd-induced AKI by enhancing TFEB activity, respectively. CONCLUSION: In summary, these findings reveal that TFEB phosphorylation, nuclear export and acetylation independently suppress TFEB activity to cause Cd-induced AKI via regulating autophagy-lysosome function, suggesting that TFEB activation might be a promising treatment strategy for Cd-induced AKI.

11.
Microorganisms ; 12(7)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39065067

RESUMO

We used inter-delta typing (IDT) and MALDI-TOF profiling to characterize the genetic and phenotypic diversity of 45 commercially available winemaking Saccharomyces cerevisiae strains and 60 isolates from an organic winemaker from Waipara, New Zealand, as a stratified approach for predicting the commercial potential of indigenous isolates. A total of 35 IDTs were identified from the commercial strains, with another 17 novel types defined among the Waipara isolates. IDT 3 was a common type among strains associated with champagne production, and the only type in commercial strains also observed in indigenous isolates. MALDI-TOF MS also demonstrated its potential in S. cerevisiae typing, particularly when the high-mass region (m/z 2000-20,000) was used, with most indigenous strains from each of two fermentation systems distinguished. Furthermore, the comparison between commercial strains and indigenous isolates assigned to IDT 3 revealed a correlation between the low-mass data (m/z 500-4000) analysis and the recommended use of commercial winemaking strains. Both IDT and MALDI-TOF analyses offer useful insights into the genotypic and phenotypic diversity of S. cerevisiae, with MALDI-TOF offering potential advantages for the prediction of applications for novel, locally isolated strains that may be valuable for product development and diversification.

12.
NPJ Vaccines ; 9(1): 135, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39085226

RESUMO

Under the dual pressure of emerging zoonoses and the difficulty in eliminating conventional zoonoses, the strategic management of bird diseases through vaccination represents a highly efficacious approach to disrupting the transmission of zoonotic pathogens to humans. Immunization with a DNA vaccine yielded limited protection against avian pathogen infection. To improve its immunogenicity, the extracellular domain of duck-derived CD40L (designated as dusCD40L) was employed as a bio-adjuvant. Our findings unequivocally established the evolutionary conservation of dusCD40L across avian species. Notably, dusCD40L exhibited a compelling capacity to elicit robust immune responses from both B and T lymphocytes. Furthermore, when employed as an adjuvant, dusCD40L demonstrated a remarkable capacity to significantly augment the titers of neutralizing antibodies and the production of IFNγ elicited by a DNA vaccine encoding the prM-E region of an avian flavivirus, namely, the Tembusu virus (TMUV). Moreover, dusCD40L could strengthen virus clearance of the prM-E DNA vaccine in ducks post-TMUV challenge. This research study presents a highly effective adjuvant for advancing the development of DNA vaccines targeting TMUV in avian hosts. Additionally, it underscores the pivotal role of duCD40L as a potent adjuvant in the context of vaccines designed to combat zoonotic infections in avian species.

13.
Sci Rep ; 14(1): 16964, 2024 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043790

RESUMO

Obesity is characterized by dysregulated adipogenesis that leads to increased number and/or size of adipocytes. Understanding the molecular mechanisms governing adipogenesis is therefore key to designing therapeutic interventions against obesity. In our study, we analyzed 3'-end sequencing data that we generated from human preadipocytes and adipocytes, as well as previously published RNA-seq datasets, to elucidate mechanisms of regulation via long non-coding RNA (lncRNA), alternative splicing (AS) and alternative polyadenylation (APA). We discovered lncRNAs that have not been previously characterized but may be key regulators of white adipogenesis. We also detected 100 AS events and, using motif enrichment analysis, identified RNA binding proteins (RBPs) that could mediate exon skipping-the most prevalent AS event. In addition, we show that usage of alternative poly(A) sites in introns or 3'-UTRs of key adipogenesis genes leads to isoform diversity, which can have significant biological consequences on differentiation efficiency. We also identified RBPs that may modulate APA and defined how 3'-UTR APA can regulate gene expression through gain or loss of specific microRNA binding sites. Taken together, our bioinformatics-based analysis reveals potential therapeutic avenues for obesity through manipulation of lncRNA levels and the profile of mRNA isoforms via alternative splicing and polyadenylation.


Assuntos
Adipogenia , Processamento Alternativo , Perfilação da Expressão Gênica , Poliadenilação , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adipogenia/genética , Humanos , Adipócitos/metabolismo , Adipócitos/citologia , Regiões 3' não Traduzidas , MicroRNAs/genética , MicroRNAs/metabolismo , Transcriptoma , Regulação da Expressão Gênica , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Biologia Computacional/métodos
14.
Chem Biol Interact ; 399: 111152, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39025289

RESUMO

Cadmium (Cd), a prevalent environmental contaminant, has attracted widespread attention due to its serious health hazards. Ferroptosis is a form of iron-dependent oxidative cell death that contributes to the development of various kidney diseases. However, the mechanisms underlying the occurrence of ferroptosis in Cd-induced renal tubular epithelial cells (TECs) have not been fully elucidated. Hereby, both in-vitro and in-vivo experiments were established to elucidate this issue. In this study, we found that Cd elicited accumulation of lipid peroxides due to intracellular ferrous ion (Fe2+) overload and glutathione depletion, contributing to ferroptosis. Inhibition of ferroptosis via chelation of Fe2+ or reduction of lipid peroxidation can significantly mitigate Cd-induced cytotoxicity. Renal transcriptome analysis revealed that the activation of heme oxygenase 1 (HO-1) was closely related to ferroptosis in Cd-induced TECs injury. Cd-induced ferroptosis and resultant TECs injury are significantly alleviated due to HO-1 inhibition, demonstrating the crucial role of HO-1 in Cd-triggered ferroptosis. Further studies showed that accumulation of lipid peroxides due to iron overload and mitochondrial ROS (mtROS) generation was responsible for HO-1-triggered ferroptosis in Cd-induced cytotoxicity. In conclusion, the current study demonstrates that excessively upregulating HO-1 promotes iron overload and mtROS overproduction to trigger ferroptosis in Cd-induced TECs injury, highlighting that targeting HO-1-mediated ferroptosis may provide new ideas for preventing Cd-induced nephrotoxicity.


Assuntos
Cádmio , Células Epiteliais , Ferroptose , Heme Oxigenase-1 , Ferro , Túbulos Renais , Mitocôndrias , Espécies Reativas de Oxigênio , Ferroptose/efeitos dos fármacos , Cádmio/toxicidade , Heme Oxigenase-1/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Animais , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/citologia , Túbulos Renais/patologia , Ferro/metabolismo , Camundongos , Peroxidação de Lipídeos/efeitos dos fármacos , Linhagem Celular , Masculino , Humanos , Glutationa/metabolismo , Camundongos Endogâmicos C57BL
15.
Nat Commun ; 15(1): 5410, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926365

RESUMO

METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of the methyltransferase complex are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase separation, by driving metabolic reprogramming. This correlates with an impairment of translation of cell-cycle related mRNAs harboring polymethylated m6A sites. In summary, our results report a coordination of m6A-dependent and -independent function of the methyltransferase complex in regulating senescence through phase separation driven by metabolic reprogramming.


Assuntos
Senescência Celular , Cromatina , Metiltransferases , Grânulos de Estresse , Metiltransferases/metabolismo , Metiltransferases/genética , Cromatina/metabolismo , Humanos , Grânulos de Estresse/metabolismo , Grânulos de Estresse/genética , Hexoquinase/metabolismo , Hexoquinase/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Adenosina/metabolismo , Adenosina/análogos & derivados , Células HEK293 , Reprogramação Metabólica , Separação de Fases
16.
Vet Res ; 55(1): 83, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943190

RESUMO

Migratory birds are important vectors for virus transmission, how migratory birds recognize viruses and viruses are sustained in birds is still enigmatic. As an animal model for waterfowl among migratory birds, studying and dissecting the antiviral immunity and viral evasion in duck cells may pave a path to deciphering these puzzles. Here, we studied the mechanism of antiviral autophagy mediated by duck STING in DEF cells. The results collaborated that duck STING could significantly enhance LC3B-II/I turnover, LC3B-EGFP puncta formation, and mCherry/EGFP ratio, indicating that duck STING could induce autophagy. The autophagy induced by duck STING is not affected by shRNA knockdown of ATG5 expression, deletion of the C-terminal tail of STING, or TBK1 inhibitor BX795 treatment, indicating that duck STING activated non-classical selective autophagy is independent of interaction with TBK1, TBK1 phosphorylation, and interferon (IFN) signaling. The STING R235A mutant and Sar1A/B kinase mutant abolished duck STING induced autophagy, suggesting binding with cGAMP and COPII complex mediated transport are the critical prerequisite. Duck STING interacted with LC3B through LIR motifs to induce autophagy, the LIR 4/7 motif mutants of duck STING abolished the interaction with LC3B, and neither activated autophagy nor IFN expression, indicating that duck STING associates with LC3B directed autophagy and dictated innate immunity activation. Finally, we found that duck STING mediated autophagy significantly inhibited duck plague virus (DPV) infection via ubiquitously degraded viral proteins. Our study may shed light on one scenario about the control and evasion of diseases transmitted by migratory birds.


Assuntos
Autofagia , Patos , Transdução de Sinais , Animais , Mardivirus/fisiologia , Interferons/metabolismo , Alphaherpesvirinae/fisiologia , Imunidade Inata , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Infecções por Poxviridae/veterinária , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/virologia
17.
Small ; : e2400740, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693082

RESUMO

Integrating self-healing capabilities into printed stretchable electronic devices is important for improving performance and extending device life. However, achieving printed self-healing stretchable electronic devices with excellent device-level healing ability and stretchability while maintaining outstanding electrical performance remains challenging. Herein, a series of printed device-level self-healing stretchable electronic devices is achieved by depositing liquid metal/silver fractal dendrites/polystyrene-block-polyisoprene-block-polystyrene (LM/Ag FDs/SIS) conductive inks onto a self-healing thermoplastic polyurethane (TPU) film via screen printing method. Owing to the fluidic properties of the LM and the interfacial hydrogen bonding and disulfide bonds of TPU, the as-obtained stretchable electronic devices maintain good electronic properties under strain and exhibit device-level self-healing properties without external stimulation. Printed self-healing stretchable electrodes possess high electrical conductivity (1.6 × 105 S m-1), excellent electromechanical properties, and dynamic stability, with only a 2.5-fold increase in resistance at 200% strain, even after a complete cut and re-healing treatment. The printed self-healing capacitive stretchable strain sensor shows good linearity (R2 ≈0.9994) in a wide sensing range (0%-200%) and is successfully applied to bio-signal detection. Furthermore, the printed self-healing electronic smart label is designed and can be used for real-time environmental monitoring, which exhibits promising potential for practical application in food preservation packaging.

18.
Food Chem ; 451: 139495, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692244

RESUMO

Our previous study revealed stem inclusion fermentation reduced anthocyanin, and increased tannin and aroma compounds responsible for green notes. This study further investigated the effect of clone selection and whole bunch fermentation on Pinot noir wine composition, with focus on tannin composition. Three treatments were conducted using two clones (AM10/5 and UCD5) in 2021 and 2022: 100% destemmed (DS), 30% whole bunch (WB30), and 60% whole bunch (WB60). WB60 increased stem and skin derived tannins but reduced seed derived tannin proportion in wines. Clone selection had an impact on tannin composition and an even greater impact on tannin concentration, colour, and aroma compounds. AM10/5 produced wines with higher tannin, polymeric pigments and darker colour. AM10/5 wines also had higher concentration of phenylethyl alcohol, but lower concentrations of 3-isobutyl-2-methoxypyrazine and ethyl esters, indicating more floral but less fruity and green notes.


Assuntos
Cor , Fermentação , Odorantes , Taninos , Vinho , Vinho/análise , Taninos/análise , Odorantes/análise , Pinus/química , Compostos Orgânicos Voláteis/química , Frutas/química , Antocianinas/análise , Antocianinas/química
19.
J Agric Food Chem ; 72(19): 10853-10861, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38708871

RESUMO

The purpose of this study was to investigate the antibacterial activity and mechanism of action of osthole against Listeria monocytogenes. The antibacterial activity of osthole was evaluated by determining the minimum inhibitory concentration (MIC) and growth curve. Cell morphology, membrane permeability, membrane integrity, bacterial physiology, and metabolism were explored using different methods to elucidate the mechanism of action of osthole. It was shown that the MIC of osthole against L. monocytogenes was 62.5 µg/mL and it inhibited the growth of L. monocytogenes effectively in a concentration-dependent manner. Scanning electron microscopy (SEM) images demonstrated morphology changes of L. monocytogenes, including rough surface, cell shrinkage, and rupture. It was found that extracellular conductivity and macromolecule content were increased significantly in the presence of osthole, indicating the disruption of cell membrane integrity and permeability. Laser confocal microscopy results supported the conclusion that osthole caused severe damage to the cell membrane. It was also noticed that osthole depleted intracellular adenosine triphosphate (ATP), inhibited Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity, and promoted the accumulation of intracellular reactive oxygen species (ROS), leading to cell death. This study suggests that osthole is a promising antibacterial agent candidate against L. monocytogenes, and it shows potential in the prevention and control of foodborne pathogens.


Assuntos
Antibacterianos , Cumarínicos , Listeria monocytogenes , Testes de Sensibilidade Microbiana , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/crescimento & desenvolvimento , Antibacterianos/farmacologia , Antibacterianos/química , Cumarínicos/farmacologia , Cumarínicos/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Trifosfato de Adenosina/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo
20.
Microbiol Spectr ; 12(7): e0422823, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38814065

RESUMO

The emergence of carbapenem-resistant Escherichia coli strains poses a considerable challenge to global public health, and little is known about carbapenemase-producing E. coli strains in Tianjin, China. This study aimed to investigate the risk factors for infections with carbapenem-resistant E. coli (CREC) strains. This retrospective case-control study was conducted at a tertiary teaching hospital. A total of 134 CREC clinical isolates were collected from the General Hospital of Tianjin Medical University between 2013 and 2020. The control group was selected at a ratio of 1:1 from patients with nosocomial carbapenem-susceptible E. coli infection. Risk factors for nosocomial CREC infection and clinical outcomes were analyzed using univariate and multivariate analyses. Multivariate analysis revealed that cephalosporin exposure (odd ratio OR = 2.01), carbapenem exposure (OR = 1.96), glucocorticoid exposure (OR = 32.45), and surgical history (OR = 3.26) were independent risk factors for CREC infection. The in-hospital mortality rate in the CREC group was 29.1%, and age >65 years (OR = 3.19), carbapenem exposure (OR = 3.54), and central venous catheter insertion (OR = 4.19) were independent risk factors for in-hospital mortality in patients with CREC infections. Several factors were identified in the development of nosocomial CREC infections. The CREC isolates were resistant to most antibiotics. Reducing CREC mortality requires a comprehensive consideration of appropriate antibiotic use, underlying diseases, and invasive procedures.IMPORTANCEEscherichia coli is an opportunistic pathogen that causes severe hospital-acquired infections. The spread of carbapenem-resistant E. coli is a global threat to public health, and only a few antibiotics are effective against these infections. Consequently, these infections are usually associated with poor prognosis and high mortality. Therefore, understanding the risk factors associated with the causes and outcomes of these infections is crucial to reduce their incidence and initiate appropriate therapies. In our study, several factors were found to be involved in nosocomial carbapenem-resistant E. coli (CREC) infections, and CREC isolates were resistant to most antibiotics. Reducing CREC mortality needs a comprehensive consideration of whether antibiotics are used appropriately, underlying diseases, and invasive interventions. These findings provide valuable evidence for the development of anti-infective therapy, infection prevention, and control of CREC-positive infections.


Assuntos
Antibacterianos , Enterobacteriáceas Resistentes a Carbapenêmicos , Carbapenêmicos , Infecção Hospitalar , Infecções por Escherichia coli , Escherichia coli , Hospitais de Ensino , Humanos , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Masculino , Feminino , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/tratamento farmacológico , Hospitais de Ensino/estatística & dados numéricos , Pessoa de Meia-Idade , China/epidemiologia , Idoso , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Estudos de Casos e Controles , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Adulto , Mortalidade Hospitalar , Idoso de 80 Anos ou mais , beta-Lactamases/metabolismo , beta-Lactamases/genética , Testes de Sensibilidade Microbiana
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