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1.
J Environ Sci (China) ; 147: 200-216, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003040

RESUMO

Microplastics (MPs) are ubiquitous in the environment, continuously undergo aging processes and release toxic chemical substances. Understanding the environmental behaviors of MPs is critical to accurately evaluate their long-term ecological risk. Generalized two-dimensional correlation spectroscopy (2D-COS) is a powerful tool for MPs studies, which can dig more comprehensive information hiding in the conventional one-dimensional spectra, such as infrared (IR) and Raman spectra. The recent applications of 2D-COS in analyzing the behaviors and fates of MPs in the environment, including their aging processes, and interactions with natural organic matter (NOM) or other chemical substances, were summarized systematically. The main requirements and limitations of current approaches for exploring these processes are discussed, and the corresponding strategies to address these limitations and drawbacks are proposed as well. Finally, new trends of 2D-COS are prospected for analyzing the properties and behaviors of MPs in both natural and artificial environmental processes.


Assuntos
Monitoramento Ambiental , Microplásticos , Microplásticos/análise , Monitoramento Ambiental/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Poluentes Químicos da Água/análise
2.
J Pharm Pract ; : 8971900241273176, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39115938

RESUMO

Background: Currently, irrational uses of medicines becoming global problem largely in developing countries like Ethiopia. Inappropriate prescribing is a major cause for poor treatment outcome and higher costs. Hence, this study was aimed to investigate medicine prescribing practice and prescription errors using WHO medicine-utilization core indicators. Methods: A hospital based retrospective cross sectional study design was used to evaluate prescribing practices and prescription errors from September to October, 2024 at the OPD pharmacy using systematic random sampling technique while a prospective approach was employed for facility indicators. Presence of potential drug-drug interactions (DDIs) were evaluated using Medscape Online Drug Interaction Checker. Data were analyzed using SPSS version 25 and interpreted as tables and figures. Results: A total of 1019 medicines were prescribed in 524 prescriptions and 81.6% (n = 832) were actually dispensed. The percentage of antibiotic, injections and medicine prescribed from Essential Drug List was 33.9% (n = 345),3.5% (n = 36) and 92.3% (n = 941) respectively. The most frequently prescribed class of medicine were antibiotics 33.9% (n = 345). 65.1% (n = 341) were ≥2 medicines and 8.3% (n = 85) had at least one potential DDIs. Among overall DDIs, the monitor closely and serious level was 60% (n = 51) and 11.8% (n = 10) respectively. The average prescription error was 4.3. Prescription errors due to failure to mention diagnosis was 40.6% (n = 213). Conclusion: Based on findings, the prescribing practices had defects to the optimum value recommended by WHO and showed high prescription errors. Antibiotics prescribing was the major problem in practice. Remarkable DDIs were observed in prescribed medicines. Therefore, designing and implementing policy to improve medicine use practice is highly indispensable.

3.
J Therm Biol ; 123: 103930, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39116624

RESUMO

Thermal limits are often used as proxies to assess the vulnerability of ectotherms to environmental change. While meta-analyses point out a relatively low plasticity of heat limits and a large interspecific variability, only few studies have compared the heat tolerance of interacting species. The present study focuses on the thermal limits, and their plasticity (heat hardening), of three species co-occurring in Western Africa: two ectoparasitoid species, Dinarmus basalis (Rondani) (Hymenoptera: Pteromalidae) and Eupelmus vuilleti (Crawford) (Hymenoptera: Eupelmidae), and their common host, Callosobruchus maculatus (F.) (Coleoptera: Bruchidae). The investigation delves into the Critical Thermal Maximum (CTmax), representing the upper tolerance limit, to understand how these species may cope with extreme thermal events. The CTmax of all three species appeared similarly high, hovering around 46.5 °C, exceeding the global mean CTmax observed in insects by 3.5 °C. Short-term exposure to moderate heat stress showed no impact on CTmax, suggesting a potential lack of heat hardening in these species. Therefore, we emphasized the similarity of heat tolerance in these interacting species, potentially stemming from both evolutionary adaptations to high temperatures during development and the stable and similar microclimate experienced by the three species over the years. While the high thermal tolerance should allow these species to endure extreme temperature events, the apparent lack of plasticity raises concerns about their ability to adapt to future climate change scenarios. Overall, this research provides valuable insights into the thermal physiology of these interacting species, providing a basis for understanding their responses to climate change and potential implications for the host-parasitoid system.

4.
Gynecol Oncol ; 190: 1-10, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39116625

RESUMO

The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has experienced rapid growth amidst the obesity epidemic in the United States. While originally developed for glucose control in Type 2 Diabetes Mellitus, the scope of these agents now extends to encompass weight loss and cardiovascular risk reduction. GLP-1RAs have the potential to induce significant weight loss, in combination with lifestyle modifications, among adults who are overweight or obese. Furthermore, these agents demonstrate efficacy in ameliorating hyperglycemia, enhancing insulin sensitivity, regulating blood pressure, improving cardiometabolic parameters, mitigating kidney dysfunction, and potentially reducing the risk of several obesity-related cancers. Drug-related toxicity is primarily gastrointestinal and active management can prevent drug discontinuation. Obesity is associated both with an increased incidence of malignancy but also with decreased survival. More research is needed to evaluate the potential use of GLP-1RA to modify the endocrine function of adipocytes, regulate the chronic inflammatory state associated with obesity, and prospective applications in oncology. These agents can impact patients with gynecologic malignancies both through their direct mechanism of action as well as potential drug toxicity.

5.
Ecol Appl ; : e3017, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118362

RESUMO

Horizon scans have emerged as a valuable tool to anticipate the incoming invasive alien species (IAS) by judging species on their potential impacts. However, little research has been conducted on quantifying actual impacts and assessing causes of species-specific vulnerabilities to particular IAS due to persistent methodological challenges. The underlying interspecific mechanisms driving species-specific vulnerabilities therefore remain poorly understood, even though they can substantially improve the accuracy of risk assessments. Given that interspecific interactions underlying ecological impacts of IAS are often shaped by phenological synchrony, we tested the hypothesis that temporal mismatches in breeding phenology between native species and IAS can mitigate their ecological impacts. Focusing on the invasive American bullfrog (Lithobates catesbeianus), we combined an environmental DNA (eDNA) quantitative barcoding and metabarcoding survey in Belgium with a global meta-analysis, and integrated citizen-science data on breeding phenology. We examined whether the presence of native amphibian species was negatively related to the presence or abundance of invasive bullfrogs and whether this relationship was affected by their phenological mismatches. The field study revealed a significant negative effect of increasing bullfrog eDNA concentrations on native amphibian species richness and community structure. These observations were shaped by species-specific vulnerabilities to invasive bullfrogs, with late spring- and summer-breeding species being strongly affected, while winter-breeding species remained unaffected. This trend was confirmed by the global meta-analysis. A significant negative relationship was observed between phenological mismatch and the impact of bullfrogs. Specifically, native amphibian species with breeding phenology differing by 6 weeks or less from invasive bullfrogs were more likely to be absent in the presence of bullfrogs than species whose phenology differed by more than 6 weeks with that of bullfrogs. Taken together, we present a novel method based on the combination of aqueous eDNA quantitative barcoding and metabarcoding to quantify the ecological impacts of biological invaders at the community level. We show that phenological mismatches between native and invasive species can be a strong predictor of invasion impact regardless of ecological or methodological context. Therefore, we advocate for the integration of temporal alignment between native and IAS's phenologies into invasion impact frameworks.

6.
Ecol Evol ; 14(8): e70096, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39108561

RESUMO

Freshwater ecosystems are increasingly affected by rising annual mean temperatures and heatwaves. While heatwaves are expected to have more immediate effects than mean temperature increases on local communities, comparative experimental studies are largely lacking. We conducted a 1-month mesocosm experiment to test the effect of different warming treatments, constantly raised temperatures (+3°C) and recurring heatwaves (+6°C), on plankton communities. We specifically tested how shifts in zooplankton trait composition and functional groups are reflected in ecosystem function (top-down control on primary producers). We found that heatwaves had a stronger and more immediate effect on zooplankton trait composition (specifically on body length and body mass) and functional groups. Heatwaves led to the decrease of small-bodied grazers (i.e., Rotifera) and the dominance of larger omnivorous Copepoda, and these shifts resulted in weaker top-down control, leading to elevated phytoplankton biomass. Altogether, our results highlight the importance of the indirect effects of heatwaves via inducing shifts in zooplankton functional groups and trait composition, which may lead to algal blooms.

7.
Acta Crystallogr E Crystallogr Commun ; 80(Pt 8): 840-844, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39108789

RESUMO

The asymmetric unit of the title compound is composed of two independent ion pairs of 4-(di-methyl-amino)-pyridin-1-ium 8-hy-droxy-quinoline-5-sulfonate (HDMAP+·HqSA-, C7H11N2 +·C9H6NO4S-) and neutral N,N-di-methyl-pyridin-4-amine mol-ecules (DMAP, C7H10N2), co-crystallized as a 1:1:1 HDMAP+:HqSA-:DMAP adduct in the monoclinic system, space group Pc. The compound has a layered structure, including cation layers of HDMAP+ with DMAP and anion layers of HqSA- in the crystal. In the cation layer, there are inter-molecular N-H⋯N hydrogen bonds between the protonated HDMAP+ mol-ecule and the neutral DMAP mol-ecule. In the anion layer, each HqSA- is surrounded by other six HqSA-, where the planar network structure is formed by inter-molecular O-H⋯O and C-H⋯O hydrogen bonds. The cation and anion layers are linked by inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions.

8.
IUCrdata ; 9(Pt 7): x240665, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39108938

RESUMO

In the title salt, [ZnCl(C23H30N4)]NO3, the central ZnII atom of the complex cation is coordinated in a square-pyramidal arrangement by four nitro-gen atoms from cyclen (1,4,7,10-tetra-aza-cyclo-dodeca-ne) in the basal plane and one chlorido ligand in the apical position. The anthracene group attached to cyclen contributes to the crystal packing through inter-molecular T-shaped π inter-actions. Additionally, the nitrate anion participates in inter-molecular N-H⋯O hydrogen bonds with cyclen.

9.
Front Plant Sci ; 15: 1439951, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39109062

RESUMO

Plant diseases are caused by various microorganisms such as bacteria, fungi, viruses, and nematodes. These diseases impact crop growth, reduce produce quality, and lead to financial losses. Plant disease can be caused by single pathogens or by interactions called "disease complexes", involving two or more pathogens. In these cases, the disease severity caused by the pathogens combined is greater than the sum of the disease caused by each pathogen alone. disease complexes formed among plant-parasitic nematodes (PPNs) with bacteria, fungi, or viruses, can occur. PPNs either enhance the other pathogen incidence and severity or are necessary for disease symptoms to be expressed. PPNs can do so by being wounding agents, vectors, modifiers of plant biochemistry and physiology, or altering the rhizosphere microbiome. This review identifies several PPNs-plant pathogens disease complexes in crop production to discuss how understanding such interactions is key for improving management practices.

10.
Cureus ; 16(7): e63935, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39109102

RESUMO

Neuromuscular blocking drugs (NMBAs) and Patent Blue V dye sodium salt 2.5% (Guerbet, Roissy, France) are frequently implicated in perioperative allergic immunoglobulin E (IgE) mediated anaphylaxis. Most cases of anaphylaxis during surgery occur at induction of anaesthesia, although reactions to vital dyes injected into soft tissues often show a delayed onset. We present the case of a female in her 60s who suffered perioperative anaphylaxis to Patent Blue V dye and possibly suxamethonium during oncological breast surgery. Allergy clinic follow-up confirmed sensitivity to both drugs which may explain the unusual bi-phasic nature of the reaction. Intradermal testing also found cross-sensitivity to methylene blue, but not to other common allergens or NMBAs. This case demonstrates the importance of thorough post-anaphylaxis follow-up and raises the possibility of cross-sensitivity between unrelated compounds.

11.
ACS Nano ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39110878

RESUMO

Electrolyte solvation chemistry regulated by lithium salts, solvents, and additives has garnered significant attention since it is the most effective strategy for designing high-performance electrolytes in lithium-ion batteries (LIBs). However, achieving a delicate balance is a persistent challenge, given that excessively strong or weak Li+-solvent coordination markedly undermines electrolyte properties, including thermodynamic redox stability and Li+-desolvation kinetics, limiting the practical applications. Herein, we elucidate the crucial influence of solvent-solvent interactions in modulating the Li+-solvation structure to enhance electrolyte thermodynamic and kinetic properties. As a paradigm, by combining strongly coordinated propylene carbonate (PC) with weakly coordinated cyclopentylmethyl ether (CPME), we identified intermolecular interactions between PC and CPME using 1H-1H correlation spectroscopy. Experimental and computational findings underscore the crucial role of solvent-solvent interactions in regulating Li+-solvent/anion interactions, which can enhance both the thermodynamic (i.e., antireduction capability) and kinetic (i.e., Li+-desolvation process) aspects of electrolytes. Additionally, we introduced an interfacial model to reveal the intricate relationship between solvent-solvent interactions, electrolyte properties, and electrode interfacial behaviors at a molecular scale. This study provides valuable insights into the critical impact of solvent-solvent interactions on electrolyte properties, which are pivotal for guiding future efforts in functionalized electrolyte engineering for metal-ion batteries.

12.
Eur J Psychol ; 20(2): 116-128, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39118999

RESUMO

Pretend play is usually defined as an activity wherein objects and actions (but also affective expression, at times) are separated from their original meanings. Its developmental appearance is set around the second year of life, and increases dramatically in duration, frequency and quality when play episodes start becoming more complex, both linguistically and interactionally reaching its peak in preschool years. To date, however, little attention has been paid to how social pretend play emerges and develops before the age of three. Our study aims to investigate early spontaneous pretend play interactions between children aged 19 to 28 months attending the same kindergarten. We used micro-analytical coding of video-recorded interactions to explore sequences of interaction where children coordinated their actions to engage in social pretend play with objects. Our analyses showed that co-constructed sequences appeared organised by a turn-alternation structure already at 19 months, and children used embodied and material resources afforded by the sequential organisation of actions to dynamically manage their participation. Although explorative, our results seem in line with previous reports suggesting an early onset of social pretend play developing over a continuum from being predominately an individual activity to progressively becoming a co-constructed endeavour.

13.
Front Cell Infect Microbiol ; 14: 1408179, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39119288

RESUMO

Introduction: Hypervirulent Klebsiella pneumoniae (hvKp) and carbapenem-resistant K. pneumoniae (CR-Kp) are rapidly emerging as opportunistic pathogens that have a global impact leading to a significant increase in mortality rates among clinical patients. Anti-virulence strategies that target bacterial behavior, such as adhesion and biofilm formation, have been proposed as alternatives to biocidal antibiotic treatments to reduce the rapid emergence of bacterial resistance. The main objective of this study was to examine the efficacy of fatty acid-enriched extract (AWME3) derived from the fat of Black Soldier Fly larvae (Hermetia illucens) in fighting against biofilms of multi-drug resistant (MDR) and highly virulent Klebsiella pneumoniae (hvKp) pathogens. Additionally, the study also aimed to investigate the potential mechanisms underlying this effect. Methods: Crystal violet (CV) and ethidium bromide (EtBr) assays show how AWME3 affects the formation of mixed and mature biofilms by the KP ATCC BAA-2473, KPi1627, and KPM9 strains. AWME3 has shown exceptional efficacy in combating the hypermucoviscosity (HMV) virulent factors of KPi1627 and KPM9 strains when tested using the string assay. The rudimentary motility of MDR KPM9 and KP ATCC BAA-2473 strains was detected through swimming, swarming, and twitching assays. The cell wall membrane disturbances induced by AWME3 were detected by light and scanning electron microscopy and further validated by an increase in the bacterial cell wall permeability and Lewis acid-base/van der Waals characteristics of K. pneumoniae strains tested by MATS (microbial adhesion to solvents) method. Results: After being exposed to 0.5 MIC (0.125 mg/ml) of AWME3, a significant reduction in the rudimentary motility of MDR KPM9 and KP ATCC BAA-2473 strains, whereas the treated bacterial strains exhibited motility between 4.23 ± 0.25 and 4.47 ± 0.25 mm, while the non-treated control groups showed significantly higher motility ranging from 8.5 ± 0.5 to 10.5 ± 0.5 mm. Conclusion: In conclusion, this study demonstrates the exceptional capability of the natural AWME3 extract enriched with a unique combination of fatty acids to effectively eliminate the biofilms formed by the highly drug-resistant and highly virulent K. pneumoniae (hvKp) pathogens. Our results highlight the opportunity to control and minimize the rapid emergence of bacterial resistance through the treatment using AWME3 of biofilm-associated infections caused by hvKp and CRKp pathogens.


Assuntos
Antibacterianos , Biofilmes , Dípteros , Farmacorresistência Bacteriana Múltipla , Ácidos Graxos , Klebsiella pneumoniae , Larva , Fatores de Virulência , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Animais , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Ácidos Graxos/metabolismo , Fatores de Virulência/metabolismo , Dípteros/microbiologia , Larva/microbiologia , Larva/efeitos dos fármacos , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Virulência/efeitos dos fármacos , Infecções por Klebsiella/microbiologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo
14.
Cureus ; 16(7): e64143, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39119376

RESUMO

Ceftriaxone and lansoprazole are commonly used in clinical settings, but recent analyses indicate a potential risk for QTc prolongation and cardiac events when used together. This case series examines three patients from a cohort of sudden death cases at a single institution over a decade, who received both medications within 24 hours before death. Three cases were identified, each with contributing factors for cardiac arrhythmias. The results underscore the importance of monitoring and possibly avoiding this drug combination in patients at risk of QT prolongation, pending further investigation into the underlying mechanisms.

15.
ACS Biomater Sci Eng ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39121180

RESUMO

High-throughput assays that efficiently link genotype and phenotype with high fidelity are key to successful enzyme engineering campaigns. Among these assays, the tyramide/peroxidase proximity labeling method converts the product of an enzymatic reaction of a surface expressed enzyme to a highly reactive fluorescent radical, which labels the cell surface. In this context, maintaining the proximity of the readout reagents to the cell surface is crucial to prevent crosstalk and ensure that short-lived radical species react before diffusing away. Here, we investigated improvements in tyramide/peroxidase proximity labeling for enzyme screening. We modified chitosan (Cs) chains with horseradish peroxidase (HRP) and evaluated the effects of these conjugates on the efficiency of proximity labeling reactions on yeast cells displaying d-amino acid oxidase. By tethering HRP to chitosan through different chemical approaches, we localized the auxiliary enzyme close to the cell surface and enhanced the sensitivity of tyramide-peroxidase labeling reactions. We found that immobilizing HRP onto chitosan through a 5 kDa PEG linker improved labeling sensitivity by over 3.5-fold for substrates processed with a low turnover rate (e.g., d-lysine), while the sensitivity of the labeling for high activity substrates (e.g., d-alanine) was enhanced by over 0.6-fold. Such improvements in labeling efficiency broaden the range of enzymes and conditions that can be studied and screened by tyramide/peroxidase proximity labeling.

16.
JMIR Hum Factors ; 11: e56924, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39092520

RESUMO

Background: The exponential growth in computing power and the increasing digitization of information have substantially advanced the machine learning (ML) research field. However, ML algorithms are often considered "black boxes," and this fosters distrust. In medical domains, in which mistakes can result in fatal outcomes, practitioners may be especially reluctant to trust ML algorithms. Objective: The aim of this study is to explore the effect of user-interface design features on intensivists' trust in an ML-based clinical decision support system. Methods: A total of 47 physicians from critical care specialties were presented with 3 patient cases of bacteremia in the setting of an ML-based simulation system. Three conditions of the simulation were tested according to combinations of information relevancy and interactivity. Participants' trust in the system was assessed by their agreement with the system's prediction and a postexperiment questionnaire. Linear regression models were applied to measure the effects. Results: Participants' agreement with the system's prediction did not differ according to the experimental conditions. However, in the postexperiment questionnaire, higher information relevancy ratings and interactivity ratings were associated with higher perceived trust in the system (P<.001 for both). The explicit visual presentation of the features of the ML algorithm on the user interface resulted in lower trust among the participants (P=.05). Conclusions: Information relevancy and interactivity features should be considered in the design of the user interface of ML-based clinical decision support systems to enhance intensivists' trust. This study sheds light on the connection between information relevancy, interactivity, and trust in human-ML interaction, specifically in the intensive care unit environment.


Assuntos
Bacteriemia , Sistemas de Apoio a Decisões Clínicas , Aprendizado de Máquina , Confiança , Humanos , Bacteriemia/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários , Interface Usuário-Computador
17.
Sci Total Environ ; 950: 175201, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39102952

RESUMO

The disparities in harmful algal blooms dynamics are largely attributed to variations in cyanobacteria populations within aquatic ecosystems. However, cyanobacteria-cyanophage interactions and their role in shaping cyanobacterial populations has been previously underappreciated. To address this knowledge gap, we isolated and sequenced 42 cyanophages from diverse water sources in China, with the majority (n = 35) originating from freshwater sources. We designated these sequences as the "Novel Cyanophage Genome sequence Collection" (NCGC). NCGC displayed notable genetic variations, with 95 % (40/42) of the sequences representing previously unidentified taxonomic ranks. By integrating NCGC with public data of cyanophages and cyanobacteria, we found evidence for more frequent historical cyanobacteria-cyanophage interactions in freshwater ecosystems. This was evidenced by a higher prevalence of prophage integrase-related genes in freshwater cyanophages (37.97 %) than marine cyanophages (7.42 %). In addition, freshwater cyanophages could infect a broader range of cyanobacteria orders (n = 4) than marine ones (n = 0). Correspondingly, freshwater cyanobacteria harbored more defense systems per million base pairs in their genomes, indicating more frequent phage infections. Evolutionary and cyanophage epidemiological studies suggest that interactions between cyanobacteria and cyanophages in freshwater and marine ecosystems are interconnected, and that brackish water can act as a transitional zone for freshwater and marine cyanophages. In conclusion, our research significantly expands the genetic information database of cyanophage, offering a wider selection of cyanophages to control harmful cyanobacterial blooms. Additionally, we represent a pioneering large-scale and comprehensive analysis of cyanobacteria and cyanophage sequencing data, and it provides theoretical guidance for the application of cyanophages in different environments.

18.
Gene ; 929: 148820, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39103059

RESUMO

BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex vascular disorder characterized by the progressive dilation of the abdominal aorta, with a high risk of rupture and mortality. Understanding the cellular interactions and molecular mechanisms underlying AAA development is critical for identifying potential therapeutic targets. METHODS: This study utilized datasets GSE197748, GSE164678 and GSE183464 from the GEO database, encompassing bulk and single-cell RNA sequencing data from AAA and control samples. We performed principal component analysis, differential expression analysis, and functional enrichment analysis to identify key pathways involved in AAA. Cell-cell interactions were investigated using CellPhoneDB, focusing on fibroblasts, vascular smooth muscle cells (VSMCs), and macrophages. We further validated our findings using a mouse model of AAA induced by porcine pancreatic enzyme infusion, followed by gene expression analysis and co-immunoprecipitation experiments. RESULTS: Our analysis revealed significant alterations in gene expression profiles between AAA and control samples, with a pronounced immune response and cell adhesion pathways being implicated. Single-cell RNA sequencing data highlighted an increased proportion of pro-inflammatory macrophages, along with changes in the composition of fibroblasts and VSMCs in AAA. CellPhoneDB analysis identified critical ligand-receptor interactions, notably collagen type I alpha 1 chain (COL1A1)/COL1A2-CD18 and thrombospondin 1 (THBS1)-CD3, suggesting complex communication networks between fibroblasts and VSMCs. In vivo experiments confirmed the upregulation of these genes in AAA mice and demonstrated the functional interaction between COL1A1/COL1A2 and CD18. CONCLUSION: The interaction between fibroblasts and VSMCs, mediated by specific ligand-receptor pairs such as COL1A1/COL1A2-CD18 and THBS1-CD3, plays a pivotal role in AAA pathogenesis.

19.
Biochim Biophys Acta Biomembr ; 1866(7): 184376, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39111381

RESUMO

Lateral heterogeneity, or mosaicity, is a fundamental property inherent to cell membranes that is crucial for their functioning. While microscopic inhomogeneities (e.g. rafts) are easily detected experimentally, lipid domains with nanoscale dimensions (nanoclusters of nanodomains, NDs) resist reliable characterization by instrumental methods. In such a case, important insight can be gained via computer modeling. Here, NDs composed of lipid's head groups in the mixed zwitterionic dioleoylphosphatidylcholine (DOPC) and negatively charged dioleoylphosphatidylserine (DOPS) bilayers were studied by molecular dynamics. A new algorithm has been developed to identify NDs. Unlike most similar methods, it implicitly considers the heterogeneous distribution of lipid head atomic density and does not require subjectively chosen parameters. In DOPS-rich membranes, lipids form more compact and stable NDs due to strong interlipid interactions. In DOPC-rich systems, NDs arise due to the "packing" effect of weakly bound lipid heads. The clustering picture is related to the physical properties of the bilayer surface: DOPS-rich systems show more pronounced surface heterogeneity of hydrophilic/hydrophobic regions compared to DOPC-rich ones. The results obtained are important for the effective quantitative characterization of the "dynamic molecular portrait" of a membrane surface - its "fingerprint" characterizing dynamical distribution of its physicochemical properties.

20.
Virus Res ; 348: 199447, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39117146

RESUMO

One third of all emerging infectious diseases are vector-borne, with no licensed antiviral therapies available against any vector-borne viruses. Zika virus and Usutu virus are two emerging flaviviruses transmitted primarily by mosquitoes. These viruses modulate different host pathways, including the PI3K/AKT/mTOR pathway. Here, we report the effect on ZIKV and USUV replication of two AKT inhibitors, Miransertib (ARQ-092, allosteric inhibitor) and Capivasertib (AZD5363, competitive inhibitor) in different mammalian and mosquito cell lines. Miransertib showed a stronger inhibitory effect against ZIKV and USUV than Capivasertib in mammalian cells, while Capivasertib showed a stronger effect in mosquito cells. These findings indicate that AKT plays a conserved role in flavivirus infection, in both the vertebrate host and invertebrate vector. Nevertheless, the specific function of AKT may vary depending on the host species. These findings indicate that AKT may be playing a conserved role in flavivirus infection in both, the vertebrate host and the invertebrate vector. However, the specific function of AKT may vary depending on the host species. A better understanding of virus-host interactions is therefore required to develop new treatments to prevent human disease and new approaches to control transmission by insect vectors.

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