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1.
J Environ Sci (China) ; 149: 585-597, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181670

RESUMO

Urban areas' performance in water, energy, infrastructure, and socio-economic sectors is intertwined and measurable through Sustainable Development Goals (SDGs) 6-13. Effective synergy among these is critical for sustainability. This study constructs an indicator framework that reflects progress towards these urban SDGs in China. Findings indicate underperformance in SDGs 8-11, suggesting the need for transformative actions. Through network analysis, the research reveals complementarities among these SDGs. Notably, the SDG space divides into socio-economic and ecological clusters, with SDG 6 (Clean Water and Sanitation) central to both. Additionally, SDG 8 (Decent Work and Economic Growth) and SDG 9 (Industry, Innovation, and Infrastructure) act as bridges, while greater synergies exist between SDG 12 (Responsible Consumption and Production) and SDG 13 (Climate Action). An in-depth view at the indicator-level shows a core-periphery structure, emphasizing indicators like SDG 6.2 (Wastewater Treatment Rate) and SDG 6.6 (Recycled Water Production Capacity per capita) as pivotal. This study confirms the urban SDG space's stability and predictiveness, underscoring its value in steering well-aligned policy decisions for sustainable growth.


Assuntos
Desenvolvimento Sustentável , Abastecimento de Água , China , Cidades , Conservação dos Recursos Naturais/métodos
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124998, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39178690

RESUMO

Soil potassium is a crucial nutrient element necessary for crop growth, and its efficient measurement has become essential for developing rational fertilization plans and optimizing crop growth benefits. At present, data mining technology based on near-infrared (NIR) spectroscopy analysis has proven to be a powerful tool for real-time monitoring of soil potassium content. However, as technology and instruments improve, the curse of the dimensionality problem also increases accordingly. Therefore, it is urgent to develop efficient variable selection methods suitable for NIR spectroscopy analysis techniques. In this study, we proposed a three-step progressive hybrid variable selection strategy, which fully leveraged the respective strengths of several high-performance variable selection methods. By sequentially equipping synergy interval partial least squares (SiPLS), the random forest variable importance measurement (RF(VIM)), and the improved mean impact value algorithm (IMIV) into a fusion framework, a soil important potassium variable selection method was proposed, termed as SiPLS-RF(VIM)-IMIV. Finally, the optimized variables were fitted into a partial least squares (PLS) model. Experimental results demonstrated that the PLS model embedded with the hybrid strategy effectively improved the prediction performance while reducing the model complexity. The RMSET and RT on the test set were 0.01181% and 0.88246, respectively, better than the RMSET and RT of the full spectrum PLS, SiPLS, and SiPLS-RF(VIM) methods. This study demonstrated that the hybrid strategy established based on the combination of NIR spectroscopy data and the SiPLS-RF(VIM)-IMIV method could quantitatively analyze soil potassium content levels and potentially solve other issues of data-driven soil dynamic monitoring.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39230810

RESUMO

The circular economy has been identified as a critical keyword for achieving the Sustainable Development Goals. Nevertheless, there is a lack of in-depth empirical literature on the impact mechanisms of the circular economy (CE) and economic growth (GDP) in mitigating e-waste generation (waste electrical and electronic equipment - WEEE). Given Europe's leading position in e-waste generation per capita, the study aims to scrutinize the interplay between CE, GDP, and WEEE for 2010-2020. The research applies advanced econometric methods, primarily centered around the system generalized method of moment and dynamic panel threshold. It was noteworthy that different CE indicators exhibited varying effects on WEEE through the econometric analysis. Therefore, the research uniquely utilized the entropy weight method to compute a holistic composite index for the circular economy (CEI) and gained some interesting findings. Firstly, CEI significantly reduced WEEE, while GDP drove its increase. However, an overly developed CEI of 0.7616 counteracted its beneficial effect. Secondly, the synergy of CEI*GDP engendered the circular economy rebound effect, diminishing environmental benefits. Thirdly, in the circular context, the environmental Kuznets curve was validated, showcasing an inverted U-shaped pattern. Finally, the study found CEI to have different threshold effects, with thresholds of 0.2161 to inhibit WEEE, 0.2114 to avert the circular economy rebound effect, and 0.2360 to leverage GDP in reducing WEEE. These outcomes give insights to policymakers in designing sound policies targeting circular economy development and decoupling e-waste generation from economic growth towards the United Nations' SDGs.

4.
Integr Med Res ; 13(3): 101052, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39219986

RESUMO

Background: Herbal medicine Ja-Geum-Jeong (JGJ) has been used for the treatment of detoxification in Eastern Asia. However, the mechanisms involved are not clearly defined. The purpose of the present study was to investigate if herb medication inhibits Methamphetamine (METH)'s reinforcing effect and also examined if a combination of herb medication and acupuncture produces a synergistic effect on METH. Methods: Male Sprague-Dawley rats were given acute METH intraperitoneally and the locomotor activity and ultrasonic vocalization (USV) calls were measured. Rats were administered JGJ orally and acupuncture was given at HT7 or SI5. Monosodium glutamate (MSG) and gamma-aminobutyric acid (GABA) agonists were injected into the Central amygdala (CeA) to investigate a possible neuroscientific mechanism. Tyrosine hydroxylase (TH) and fast scan cyclic voltammetry (FSCV) were measured to immunohistochemically and electrically confirm the behavioral data. Results: Locomotor activity and USV calls were increased by METH (P < 0.05) and these increases were inhibited by JGJ (P < 0.05). Also, JGJ had no effect on the normal group given saline, and acupuncture at SI5 acupoint, but not at HT7 acupoint, produced a synergistic effect when combined with JGJ (P < 0.05). The JGJ's inhibition was blocked by the inactivation of CeA (P < 0.05), and MSG mimicked JGJ (P < 0.05). TH and FSCV measures showed the same pattern with the behavioral data (P < 0.05). Conclusion: Results of the present study suggest that JGJ had inhibitory effects on the METH which was mediated through the activation of CeA and that combination of acupuncture and herb produced synergistic effect.

5.
J Biomech ; 176: 112305, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39260234

RESUMO

This study investigated the covariate structure of each segmental angle that stabilize the center of mass (COM) in the mediolateral and vertical directions in response to knee joint movement in individuals with knee osteoarthritis (KOA) using uncontrolled manifold (UCM) analysis. Twenty individuals with KOA and 13 healthy controls participated in this cross-sectional study. Kinematic and kinetic data were collected during level walking. UCM analysis was used to determine the covariance structure of segment angles stabilizing the COM in the mediolateral and vertical directions. The results indicated reduced knee flexion movement during the stance phase in the KOA group. In the mediolateral direction, the KOA group exhibited increased kinematic synergy stabilizing the COM. However, in the vertical direction, decreased kinematic synergy was observed. KOA group demonstrated greater trial-to-trial variances in segmental angles constituting the knee joint, suggesting enhanced covariance structure attempting to stabilize the COM in the mediolateral direction but increasing variability that destabilizes the COM in the vertical direction. Furthermore, decreased knee flexion movement during loading response may lead to reduced vertical kinematic synergy. In conclusion, these findings underscore the need to address improving knee flexion movement during the loading response to prevent osteoarthritis progression in patients with KOA. It provides insights into interventions focusing on improving knee flexion and enhancing kinematic synergy in the vertical direction, potentially benefiting patients with KOA.

6.
J Exp Clin Cancer Res ; 43(1): 259, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261955

RESUMO

Patient-derived organoids (PDOs) established from tissues from various tumor types gave the foundation of ex vivo models to screen and/or validate the activity of many cancer drug candidates. Due to their phenotypic and genotypic similarity to the tumor of which they were derived, PDOs offer results that effectively complement those obtained from more complex models. Yet, their potential for predicting sensitivity to combination therapy remains underexplored. In this review, we discuss the use of PDOs in both validation and optimization of multi-drug combinations for personalized treatment strategies in CRC. Moreover, we present recent advancements in enriching PDOs with diverse cell types, enhancing their ability to mimic the complexity of in vivo environments. Finally, we debate how such sophisticated models are narrowing the gap in personalized medicine, particularly through immunotherapy strategies and discuss the challenges and future direction in this promising field.


Assuntos
Neoplasias Colorretais , Organoides , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Medicina de Precisão/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
7.
BMC Microbiol ; 24(1): 333, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39251899

RESUMO

Pichia kudriavzevii (formerly Candida krusei) poses a significant threat to immunocompromised patients due to its inherent resistance to various antifungal drugs. This study explored the anticandidal potential of citral, linalool, and carvacrol in combination with nystatin against P. kudriavzevii strains.Using the microdilution method following CLSI guidelines, Minimum Inhibitory Concentrations (MICs) and fungicidal concentrations (MFCs) were determined. Citral exhibited MIC values ranging from 50 to 100 µg/ml, averaging 70.24 ± 16.99 µg/ml, while carvacrol had MIC values of 50 to 100 µg/ml, averaging 86.90 ± 16.99 µg/ml. Linalool demonstrated weaker antifungal activity, with MIC values between 100 and 200 µg/ml, averaging 150 ± 38.73 µg/ml. The study assessed the synergistic effectsof these phenols with nystatin through fractional inhibitory concentration indices (FICIS). In addition, flow cytometry was employed to assess apoptosis induction in P. kudriavzevii cells.Carvacrol displayed a remarkable synergistic effect in combination with nystatin against all 21 isolates tested. Conversely, linalool showed synergy in 17 isolates, while citral exhibited synergy in only 2 isolates. These findings highlight distinct patterns of synergy between the different compounds and nystatin against P. kudriavzevii. Also, Carvacrol emerged as the most potent inducer of apoptosis across all P. kudriavzevii strains, followed by citral and linalool. This suggests that carvacrol not only possesses a stronger antifungal effect but also has a more pronounced ability to trigger programmed cell death in P. kudriavzevii. In conclusion, the study supports the potential of carvacrol, citral and linalool, as anticandidal agents, suggesting their supplementation with nystatin for treating P. kudriavzevii infections.


Assuntos
Monoterpenos Acíclicos , Antifúngicos , Apoptose , Cimenos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Monoterpenos , Nistatina , Pichia , Antifúngicos/farmacologia , Cimenos/farmacologia , Monoterpenos Acíclicos/farmacologia , Nistatina/farmacologia , Apoptose/efeitos dos fármacos , Humanos , Monoterpenos/farmacologia , Pichia/efeitos dos fármacos , Pichia/isolamento & purificação
8.
Int J Pharm X ; 8: 100272, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39252692

RESUMO

Mulberry Diels-Alder-type adducts (MDAAs), isolated from Morus alba root bark, exhibit dual activity against viral and bacterial pathogens but show sobering efficacy following oral administration. Inhalation administration may overcome issues with oral bioavailability and improve efficacy for the treatment of respiratory infections. To assess the suitability of MDAAs for inhalation administration, physicochemical (e.g. pH, pKa, logP, pH-dependent solubility) and biopharmaceutical (epithelial cytotoxicity, permeability, and uptake) properties of two bioactive MDAA stereoisomers sanggenon C (SGC) and sanggenon D (SGD) were evaluated as isolated natural compounds and within parent extracts (MA21, MA60). Despite their structural similarity, SGD exhibited a 10-fold higher solubility than SGC across pH 1.2-7.4, with slight increases at neutral pH. Both compounds were more soluble in isolated form than in the parent extracts. The more lipophilic SGC was found to be more cytotoxic when compared to SGD, indicating a better cellular penetration, which was confirmed by uptake studies. Nonetheless, SGC and SGD exhibited no measurable permeability across intact Calu-3 monolayers, highlighting their potential for increased lung retention and improved local anti-infective activity following inhalation administration. Results suggest that SGC and SGD in isolated form, rather than as extracts, are promising candidates for pulmonary drug delivery to treat lung infections.

9.
Physiol Meas ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39231477

RESUMO

OBJECTIVE: Accurate prediction of unmearsured muscle excitations can reduce the required wearable surface electromyography (sEMG) sensors, which is a critical factor in the study of physiological measurement. Synergy extrapolation uses synergy excitations as building blocks to reconstruct muscle excitations. However, the practical application of synergy extrapolation is still limited as the extrapolation process utilizes unmeasured muscle excitations it seeks to reconstruct. This paper aims to propose and derive methods to provide an avenue for the practical application of synergy extrapolation with non-negative matrix factorization (NMF) methods. APPROACH: Specifically, a tunable Gaussian-Laplacian mixture distribution NMF (GLD-NMF) method and related multiplicative update rules are derived to yield appropriate synergy excitations for extrapolation. Furthermore, a template-based extrapolation structure (TBES) is proposed to extrapolate unmeasured muscle excitations based on synergy weighting matrix templates totally extracted from measured sEMG datasets, improving the extrapolation performance. Moreover, we applied the proposed GLD-NMF method and TBES to selected muscle excitations acquired from a series of single-leg stance (SLS) tests, walking tests and upper limb reaching tests. MAIN RESULTS: Experimental results show that the proposed GLD-NMF and TBES could extrapolate unmeasured muscle excitations accurately. Moreover, introducing synergy weighting matrix templates could decrease the number of sEMG sensors in a series of experiments. In addition, verification results demonstrate the feasibility of applying synergy extrapolation with NMF methods. SIGNIFICANCE: With the TBES method, synergy extrapolation could play a significant role in reducing data dimensions of sEMG sensors, which will improve the portability of sEMG sensors-based systems and promotes applications of sEMG signals in human-machine interfaces scenarios.

10.
Ying Yong Sheng Tai Xue Bao ; 35(7): 1925-1934, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39233422

RESUMO

Clarifying the matching degree and the trade-offs and synergies between supply and demand of ecosystem services is of significance for scientific division of management zoning and sustainable urban development. We calculated the supply and demand of ecosystem services at the sub-district (town) scale of Taiyuan based on multi-source data, explored the coldspots and hotspots area of the supply-demand ratio and the trade-offs and synergies of six ecosystem services using the Getis-Ord Gi* tool and correlation analysis, and proposed strategies based on the regional characteristics of natural-resource and socio-economy. Results showed the distribution of the supply and demand of ecosystem services had a spatial heterogeneity. In terms of supply, the area with high supply of carbon storage, air purification, thermal environment regulation and recreation service were located in the east and west parts, that of soil conservation in the west and water yield in the south part. In terms of demand, the demand distribution of carbon storage, thermal environment regulation, water yield and recreation service were characterized by high in the central and east-south area, and low in the periphery, and high demand of air purification in south and north parts, soil conservation in west part. There were substantial mismatches between the demand and supply of ecosystem services. The risk levels of the supply and demand of six ecosystem services showed a decreasing pattern from the Fenhe River to the eastern and western mountains. There were trade-offs between water yield and other five ecosystem services in their supply, while air purification and soil conservation had trade-offs with other four ecosystem services in demand. Based on the regional ecological management framework, we divided the study area into three primary zones and eight secondary zones, and proposed differentiated ecological management strategies to provide theoretical support for ecological zoning. The results could provide a basis for balancing the relationship of supply and demand of ecosystem services and promoting the sustainable development of the city.


Assuntos
Cidades , Conservação dos Recursos Naturais , Ecossistema , China , Ecologia , Monitoramento Ambiental
11.
Front Microbiol ; 15: 1468792, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39224218

RESUMO

Black rot, caused by Xanthomonas campestris pv. campestris (Xcc), is considered the most destructive disease affecting cruciferous vegetables, resulting in significant losses worldwide. The need for biocontrol agents against Xcc that can reduce reliance on chemical pesticides, enhance sustainability, and ensure crops and environmental health is crucial. Combining phages with other antibacterial agents (i.e., antibiotics and bacteriocins) to treat bacterial infections is gaining increased attention due to the frequently observed synergistic effects. This study introduces for the first time the combination of a lytic phage, i.e., Xylella phage MATE 2 (MATE 2) with nisin-producing Lactococcus lactis subsp. lactis (L. lactis) bacterium as an eco-friendly, cost-effective, and practical strategy for controlling Xcc in cruciferous vegetables. The antibacterial efficacy of MATE 2 and L. lactis, individually and in combination, against Xcc was investigated through a series of in vitro assays and in planta experiments conducted on broccoli plants. The time-killing curves results showed that under conditions of reduced Xcc population concentration (103 CFU/mL), MATE 2 at 108 PFU/mL exerted a persistent inhibitory effect on Xcc growth for 7 days. The Spot assays and v-qPCR analysis showed that both L. lactis and its bacteriocin nisin have significant antibacterial potential to contrast Xcc. Furthermore, combined application of MATE 2 and L. lactis in broccoli plants by foliar spraying generated significant synergistic efficacy in preventing Xcc infections, achieving a 71% reduction in symptoms, compared with 64 and 38% for single applications, respectively. In this study, the positive synergistic effect of the combined application of phage and beneficial bacteria in preventing black rot disease underscores this eco-friendly and cost-effective approach as a promising control measure against plant bacterial diseases.

12.
J Environ Manage ; 369: 122358, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39226811

RESUMO

Public service sectors play crucial roles in maintaining societal functioning through the provision of essential services. However, amidst the backdrop of air pollution, their developmental trajectories may veer off course from their intended goals. Quantifying the impact of air pollution on public service sectors, particularly from an employment perspective, offers valuable insights for policymakers aiming to foster the sustainable growth of these sectors and expand the analysis framework on air pollution externalities. Drawing on monthly data spanning from January 2015 to December 2019 across 269 prefecture cities, this paper therefore explores the impact of air pollution on public service sector employment using a cross-lagged panel model with fixed effects. I find that air pollution negatively affects the employment scales in public service sectors. This negative employment shock is also unevenly distributed across areas and sub-sectors and intensifies over time. Cities belong to key areas for air pollution prevention and control, small and medium-sized cities, and secondary-industry dominated cities, suffer disproportionately negative employment shocks in their public service sectors. These findings offer actionable insights for policymakers to implement targeted measures supporting the continued growth of public service sectors and deepen understanding of the economic ramifications of air pollution.

13.
New Phytol ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238109

RESUMO

Plant chemodiversity, the diversity of plant-specialized metabolites, is an important dimension of biodiversity. However, there are so far few mathematical models to test verbal hypotheses on how chemodiversity evolved. Here, we develop such a model to test predictions of five hypotheses: the 'fluctuating selection hypothesis', the 'dominance reversal hypothesis', the interaction diversity hypothesis, the synergy hypothesis, and the screening hypothesis. We build a population genetic model of a plant population attacked by herbivore species whose occurrence fluctuates over time. We study the model using mathematical analysis and individual-based simulations. As predicted by the 'dominance reversal hypothesis', chemodiversity can be maintained if alleles conferring a defense metabolite are dominant with respect to the benefits, but recessive with respect to costs. However, even smaller changes in dominance can maintain polymorphism. Moreover, our results underpin and elaborate predictions of the synergy and interaction diversity hypotheses, and, to the extent that our model can address it, the screening hypotheses. By contrast, we found only partial support for the 'fluctuating selection hypothesis'. In summary, we have developed a flexible model and tested various verbal models for the evolution of chemodiversity. Next, more mechanistic models are needed that explicitly consider the organization of metabolic pathways.

14.
J Sports Sci Med ; 23(1): 571-580, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39228767

RESUMO

Basketball victory relies on an athlete's skill to make precise shots at different distances. While extensive research has explored the kinematics and dynamics of different shooting distances, the specific neuromuscular control strategies involved remain elusive. This study aimed to compare the differences in muscle synergies during basketball shooting at different distances, offering insights into neuromuscular control strategies and guiding athletes' training. Ten skilled shooting right-handed male basketball players participated as subjects in this experiment. Electromyographic (EMG) data for full-phase shooting were acquired at short (3.2 m), middle (5.0 m), and long (6.8 m) distances. Non-negative matrix decomposition extracted muscle synergies (motor modules and motor primitives) during shooting. The results of this study show that all three distance shooting can be broken down into three synergies and that there were differences in the synergies between short and long distances, with differences in motor primitive 1 and motor primitive 2 at the phase of 45% - 59% (p < 0.001, t* = 4.418), and 78% - 88% (p < 0.01, t* = 4.579), respectively, and differences in the motor module 3 found in the differences in muscle weights for rectus femoris (RF) (p = 0.001, d = -2.094), and gastrocnemius lateral (GL) (p = 0.001, d = -2.083). Shooting distance doesn't affect the number of muscle synergies in basketball shooting but alters synergy patterns. During long distance shooting training, basketball players should place more emphasis on the timing and synergistic activation of upper and lower limbs, as well as core muscles.


Assuntos
Basquetebol , Eletromiografia , Destreza Motora , Músculo Esquelético , Humanos , Basquetebol/fisiologia , Masculino , Adulto Jovem , Fenômenos Biomecânicos , Músculo Esquelético/fisiologia , Destreza Motora/fisiologia , Adulto , Desempenho Atlético/fisiologia
15.
Cell Rep ; 43(9): 114710, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39240715

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges for targeted clinical interventions due to prevalent KRAS mutations, rendering PDAC resistant to RAF and MEK inhibitors (RAFi and MEKi). In addition, responses to targeted therapies vary between patients. Here, we explored the differential sensitivities of PDAC cell lines to RAFi and MEKi and developed an isogenic pair comprising the most sensitive and resistant PDAC cells. To simulate patient- or tumor-specific variations, we constructed cell-line-specific mechanistic models based on protein expression profiling and differential properties of KRAS mutants. These models predicted synergy between two RAFi with different conformation specificity (type I½ and type II RAFi) in inhibiting phospho-ERK (ppERK) and reducing PDAC cell viability. This synergy was experimentally validated across all four studied PDAC cell lines. Our findings underscore the need for combination approaches to inhibit the ERK pathway in PDAC.

16.
Plant Sci ; : 112244, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39244093

RESUMO

Co-infection, caused by multiple pathogen attacks on an organism, can lead to disease development or immunity. This complex interaction can be synergetic, co-existing, or antagonistic, ultimately influencing disease severity. The interaction between fungus, bacterium, and virus (three kingdom pathogens) is most prevalent. However, the underlying mechanisms of co-infection need to be explored further. In this study, we investigated the co-infection phenomenon in rice plants exposed to multiple pathogen species, specifically Rice necrosis mosaic virus (RNMV) and rice blast fungus (Magnaporthe oryzae, MO), bacterial leaf blight (Xanthomonas oryzae pv. oryzae, XO) or Cucumber mosaic virus (CMV). Our research showed that RNMV interacts synergistically with MO, XO, or CMV, increasing pathogen growth and lesion size. These findings suggest positive synergy in RNMV co-infections with three kingdom pathogens, increasing accumulation and symptoms. Additionally, to investigate the role of RNAi in pathogen synergism, we analyzed rice mutant lines deficient in RNA-dependent RNA polymerase 1 (OsRDR1) or 6 (OsRDR6). Notably, we observed the loss of synergy in each mutant line, highlighting the crucial role of OsRDR1 and OsRDR6 in maintaining the positive interaction between RNMV and three kingdom pathogens. Hence, our study emphasized the role of the RNA silencing pathway in the intricate landscape of pathogen interactions; the study's outcome could be applied to understand the plant defense response to improve crop yields.

17.
mBio ; : e0139324, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248568

RESUMO

Phage-antibiotic synergy (PAS) represents a superior treatment strategy for pathogen infections with less probability of resistance development. Here, we aim to understand the molecular mechanism by which PAS suppresses resistance in terms of population evolution. A novel hypervirulent Klebsiella pneumoniae (KP) phage H5 was genetically and structurally characterized. The combination of H5 and ceftazidime (CAZ) showed a robust synergistic effect in suppressing resistance emergence. Single-cell Raman analysis showed that the phage-CAZ combination suppressed bacterial metabolic activities, contrasting with the upregulation observed with phage alone. The altered population evolutionary trajectory was found to be responsible for the contrasting metabolic activities under different selective pressures, resulting in pleiotropic effects. A pre-existing wcaJ point mutation (wcaJG949A) was exclusively selected by H5, conferring a fitness advantage and up-regulated activity of carbohydrate metabolism, but also causing a trade-off between phage resistance and collateral sensitivity to CAZ. The wcaJ point mutation was counter-selected by H5-CAZ, inducing various mutations in galU that imposed evolutionary disadvantages with higher fitness costs, and suppressed carbohydrate metabolic activity. H5 and H5-CAZ treatments resulted in opposite effects on the transcriptional activity of the phosphotransferase system and the ascorbate and aldarate metabolism pathway, suggesting potential targets for phage resistance suppression. Our study reveals a novel mechanism of resistance suppression by PAS, highlighting how the complexity of bacterial adaptation to selective pressures drives treatment outcomes. IMPORTANCE: Phage-antibiotic synergy (PAS) has been recently proposed as a superior strategy for the treatment of multidrug-resistant pathogens to effectively reduce bacterial load and slow down both phage and antibiotic resistance. However, the underlying mechanisms of resistance suppression by PAS have been poorly and rarely been studied. In this study, we tried to understand how PAS suppresses the emergence of resistance using a hypervirulent Klebsiella pneumoniae (KP) strain and a novel phage H5 in combination with ceftazidime (CAZ) as a model. Our study reveals a novel mechanism by which PAS drives altered evolutionary trajectory of bacterial populations, leading to suppressed emergence of resistance. The findings advance our understanding of how PAS suppresses the emergence of resistance, and are imperative for optimizing the efficacy of phage-antibiotic therapy to further improve clinical outcomes.

18.
Adv Mater ; : e2407707, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39246197

RESUMO

Bacteria share a longstanding and complex relationship with humans, playing a role in protecting gut health and sustaining the ecosystem to cause infectious diseases and antibiotic resistance. Luminogenic materials that share aggregation-induced emission (AIE) characteristics have emerged as a versatile toolbox for bacterial studies through fluorescence visualization. Numerous research efforts highlight the superiority of AIE materials in this field. Recent advances in AIE materials in bacterial studies are categorized into four areas: understanding bacterial interactions, antibacterial strategies, diverse applications, and synergistic applications with bacteria. Initial research focuses on visualizing the unseen bacteria and progresses into developing strategies involving electrostatic interactions, amphiphilic AIE luminogens (AIEgens), and various AIE materials to enhance bacterial affinity. Recent progress in antibacterial strategies includes using photodynamic and photothermal therapies, bacterial toxicity studies, and combined therapies. Diverse applications from environmental disinfection to disease treatment, utilizing AIE materials in antibacterial coatings, bacterial sensors, wound healing materials, etc., are also provided. Finally, synergistic applications combining AIE materials with bacteria to achieve enhanced outcomes are explored. This review summarizes the developmental trend of AIE materials in bacterial studies and is expected to provide future research directions in advancing bacterial methodologies.

19.
Sci Rep ; 14(1): 20894, 2024 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-39245771

RESUMO

This study proposes an innovative approach to combat the escalating threat of antibiotic resistance in bacteria by introducing a novel ZnO-propolis nanocomposite (ZnO-P NCs). The overuse of antibiotics, particularly during events like the COVID-19 pandemic, has intensified bacterial resistance, necessitating innovative solutions. The study employs a cost-effective and controllable biosynthesis method to produce ZnO nanoparticles (ZnO-NPs), with propolis extract crucially contributing to the reduction and stabilization of Zn2+ ions. A biodegradable nano-propolis matrix is then created by incorporating ZnO-NPs, forming the ZnO-P NCs. Structural stability is confirmed through FT-IR and Zeta potential analysis, while nanoscale properties are validated via TEM, SEM, and XRD analyses. The antimicrobial efficacy of various substances, including propolis, nano propolis, ethanolic propolis extract, ZnO-NPs, and ZnO-P NCs, is assessed against Gram-negative and Gram-positive bacteria, alongside a comparison with 28 antibiotics. Among the bacteria tested, Pseudomonas aeruginosa PAO1 ATCC15692 was more sensitive (40 mm) to the biosynthesized nanocomposite ZnO-P NCs than to ZnO-NPs (38 mm) and nanopropolis (32 mm), while Escherichia coli was resistant to nanopropolis (0 mm) than to ZnO-NPs (31 mm), and ZnO-P NCs (34 mm). The study reveals a synergy effect when combining propolis with green-synthesized ZnO-NPs in the form of ZnO-P NCs, significantly improving their efficiency against all tested bacteria, including antibiotic-resistant strains like E. coli. The nanocomposite outperforms other materials and antibiotics, demonstrating remarkable antibacterial effectiveness. SEM imaging confirms the disruption of bacterial cell membranes by ZnO-NPs and ZnO-P NCs. The study emphasizes the potential applications of ZnO-NPs integrated into biodegradable materials and underscores the significance of the zinc oxide-propolis nanocomposite in countering antimicrobial resistance. Overall, this research offers a comprehensive solution to combat multidrug-resistant bacteria, opening avenues for novel approaches in infection control.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Nanocompostos , Própole , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Própole/química , Própole/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Nanocompostos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas Metálicas/química
20.
Lett Appl Microbiol ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39257244

RESUMO

Histone acetyltransferase inhibitors (HATi) are mechanism-based inhibitors that show promise in the treatment of several illnesses, including diabetes, hyperlipidemia, cancer, and Alzheimer's disease. The work emphasizes the significance of HATi as a possible treatment strategy against Candida species biofilms. Here, in this study, we found that combining a HATi, anacardic acid, and quercetin, a known flavonoid, significantly prevented biofilm formation by C. tropicalis. We further show that C. tropicalis exhibited a considerable downregulation of drug-resistance gene expression (CDR1 and MDR1) when co-administrated. Additionally, in silico studies revealed that the anacardic acid (AA) interacts strongly with a histone acetyltransferase, Rtt109, which may account for the observed biofilm inhibitory effect. In conclusion, the study illustrates how HATi may be used to potentiate the inhibitory action of phytoactives or antifungals against drug-resistant yeast infections.

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