HER2 puzzle pieces: Non-Coding RNAs as keys to mechanisms, chemoresistance, and clinical outcomes in Ovarian cancer.

Ovarian cancer (OC) presents significant challenges, characterized by limited treatment options and therapy resistance often attributed to dysregulation of the HER2 signaling pathway. Non-coding RNAs (ncRNAs) have emerged as key players in regulating gene expression in OC. This comprehensive review underscores the pivotal role of ncRNAs in modulating HER2 signaling, with a specific focus on their mechanisms, impact on chemoresistance, and prognostic/diagnostic implications. MicroRNAs, long non-coding RNAs, and circular RNAs have been identified as essential regulators in the modulation of the HER2 pathway. By directly targeting key components of the HER2 axis, these ncRNAs influence its activation and downstream signaling cascades. Dysregulated ncRNAs have been closely associated with chemoresistance, leading to treatment failures and disease progression in OC. Furthermore, distinct expression profiles of ncRNAs hold promise as reliable prognostic and diagnostic markers, facilitating personalized treatment strategies and enhancing disease outcome assessments. A comprehensive understanding of how ncRNAs intricately modulate HER2 signaling is imperative for the development of targeted therapies and the improvement of patient outcomes. The integration of ncRNA profiles into clinical practice has the potential to enhance prognostic and diagnostic accuracy in the management of ovarian cancer. Further research efforts are essential to validate the clinical utility of ncRNAs and elucidate their precise roles in the regulation of HER2 signaling. In conclusion, ncRNAs play a crucial role in governing HER2 signaling in ovarian cancer, impacting chemoresistance and providing valuable prognostic and diagnostic insights. The exploration of ncRNA-mediated HER2 modulation offers promising avenues for the development of personalized treatment approaches, ultimately advancing patient care and outcomes in OC.

Identification and Visualization of Polystyrene Microplastics/Nanoplastics in Flavored Yogurt by Raman Imaging.

The contamination of food by microplastics has garnered widespread attention, particularly concerning the health risks associated with small-sized microplastics. However, detecting these smaller microplastics in food poses challenges attributed to the complexity of food matrices and instrumental and method limitations. Here, we employed Raman imaging for visualization and identification of polystyrene particles synthesized in polymerization reactions, ranging from 400 to 2600 nm. We successfully developed a quantitative model of particle size and concentration for polystyrene, exhibiting excellent fit (R2 of 0.9946). We established procedures for spiked flavored yogurt using synthesized polystyrene, providing fresh insights into microplastic extraction efficiency. Recovery rates calculated from models validated the method's feasibility. In practical applications, the assessment of the size, type, shape, and quantity of microplastics in unspiked flavored yogurt was conducted. The most common polymers found were polystyrene, polypropylene, and polyethylene, with the smallest polystyrene sizes ranging from 1 to 10 µm. Additionally, we conducted exposure assessments of microplastics in branded flavored yogurt. This study established a foundation for developing a universal method to quantify microplastics in food, covering synthesis of standards, method development, validation, and application.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Exploring the binding mechanism and adverse toxic effects of degradation metabolites of pyrethroid insecticides to human serum albumin: Multi-spectroscopy, calorimetric and molecular docking approaches.

Pyrethroid insecticides (PIs), a class of structurally similar non-persistent organic pollutants, can be degraded and metabolized to more toxic, and longer half-life products. In this study, the binding interaction mechanisms between human serum albumin (HSA) and the main degradation metabolites of PIs, 3-phenoxybenzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), were studied by theoretical simulation and experimental verification. Steady state fluorescence spectra showed that the fluorescence quenching mechanism was static. According to the binding constant, 4-F-3-PBA (1.53 × 105 L mol-1) was bound more strongly to HSA than 3-PBA (1.42 × 105 L mol-1) in subdomain ⅡA (site I). It was found by isothermal titration calorimetry that the metabolites and HSA spontaneously combined mainly through hydrogen bond and van der Waals interaction. Ultraviolet absorption spectra and circular dichroism spectra showed that the metabolites caused slight changes in the microenvironment and conformation of HSA. The above results were proved by molecular docking. The toxicity properties of the metabolites were further analyzed by software, and 4-F-3-PBA was found to be more toxic than 3-PBA. Considering the high exposure level of these metabolites in food, the environment and human body, it is necessary to further explore the toxicity of PIs metabolites.

Visual Colorimetric Detection of Edible Oil Freshness for Peroxides Based on Nanocellulose.

Traditional methods for evaluating the edibility of lipids involve the use of organic reagents and complex operations, which limit their routine use. In this study, nanocellulose was prepared from bamboo, and a colorimetric reading strategy based on nanocellulose composite hydrogels was explored to monitor the freshness of edible oils. The hydrogels acted as carriers for peroxide dyes that changed color according to the freshness of the oil, and color information was digitized using UV-vis and RGB analysis. The sensitivity and accuracy of the hydrogel were verified using H2O2, which showed a linear relationship between absorbance and H2O2 content in the range of 0-0.5 and 0.5-11 mmol/kg with R2 of 0.9769 and 0.9899, respectively, while the chromatic parameter showed an exponential relationship with R2 of 0.9626. Surprisingly, the freshness of all seven edible oil samples was correctly identified by the hydrogel, with linear correlation coefficients greater than 0.95 in the UV-vis method and exponential correlation coefficients greater than 0.92 in the RGB method. Additionally, a peroxide value color card was established, with an accuracy rate of 91.67%. This functional hydrogel is expected to be used as a household-type oil freshness indicator to meet the needs of general consumers.

Extraction, bioactive function and application of wheat germ protein/peptides: A review.

The aging population and high incidence of age-related diseases are major global societal issues. Consuming bioactive substances as part of our diet is increasingly recognized as essential for ensuring a healthy life for older adults. Wheat germ protein has a reasonable peptide structure and amino acid ratio but has not been fully utilized and exploited, resulting in wasted wheat germ resources. This review summarizes reformational extraction methods of wheat germ protein/peptides (WGPs), of which different methods can be selected to obtain various WGPs. Interestingly, except for some bioactive activities found earlier, WGPs display potential anti-aging activity, with possible mechanisms including antioxidant, immunomodulatory and intestinal flora regulation. However, there are missing in vitro and in vivo bioactivity assessments of WGPs. WGPs possess physicochemical properties of good foamability, emulsification and water retention and are used as raw materials or additives to improve food quality. Based on the above, further studies designing methods to isolate particular types of WGPs, determining their nutritional and bioactive mechanisms and verifying their activity in vivo in humans are crucial for using WGPs to improve human health.

Application of a Novel Au@ZIF-8 Composite in the Detection of Bisphenol A by Surface-Enhanced Raman Spectroscopy.

Bisphenol A (BPA) is an endocrine disruptor which is widely present in fish under the influence of environmental pollution. It is essential to establish a rapid detection method for BPA. Zeolitic imidazolate framework (ZIF-8) is a typical metal-organic framework material (MOFs) with a strong adsorption capacity, which can effectively adsorb harmful substances in food. Combining MOFs and surface-enhanced Raman spectroscopy (SERS) can achieve rapid and accurate screening of toxic substances. In this study, a rapid detection method for BPA was established by preparing a new reinforced substrate Au@ZIF-8. The SERS detection method was optimized by combining SERS technology with ZIF-8. The Raman peak at 1172 cm-1 was used as the characteristic quantitative peak, and the lowest detection concentration of BPA was as low as 0.1 mg/L. In the concentration range of 0.1~10 mg/L, the linear relationship between SERS peak intensity and the concentration of BPA was good, and R2 was 0.9954. This novel SERS substrate was proven to have great potential in rapidly detecting BPA in food.

Characterization of the interaction between boscalid and tannic acid and its effect on the antioxidant properties of tannic acid.

The binding of pesticide residues and fruit components may have a profound impact on pesticide dissipation and the functional characteristics of the corresponding components. Therefore, the interaction between boscalid and tannic acid (TA, a representative phenolic in fruit) was systematically investigated using spectroscopic, thermodynamic, and computational chemistry methods. A separable system was designed to obtain the boscalid-TA complex. Fourier transform infrared and 1 H-NMR spectroscopies indicated the formation of hydrogen bonds in the complex. Isothermal titration calorimetry showed that the complex bound spontaneously through hydrophobic interactions (ΔG < 0, ΔH > 0, ΔS > 0), with a binding constant of 6.0 × 105  M-1 at 298 K. The molecular docking results further confirmed the formation of hydrogen bonds and hydrophobic interactions in the complex at the molecular level, with a binding energy of -8.43 kcal mol-1 . In addition, the binding of boscalid to TA significantly decreased the antioxidant activity of TA. The binding of boscalid residue to TA was characterized at the molecular level, which significantly reduced the in vitro antioxidant properties of TA. PRACTICAL APPLICATION: This study provides a reference for the molecular mechanisms of the interaction between pesticide residues and food matrices, as well as a basis for regulating bound-state pesticide residues in food.

Role of the gut microbiota in dietary patterns rich in torularhodin via OSA colon-targeted delivery.

Torularhodin is a carotenoid with various functions, and carotenoids can be used by the gut microbiota. However, the effect of torularhodin on the gut microbiota is not yet clear. In this study, an octenyl succinic anhydride (OSA) colon-targeted delivery system and an in vitro gut digestive system were used to explore the role of the gut microbiota in long-term dietary patterns rich in torularhodin. The results suggested that the gut microbiota was affected by the diet rich in torularhodin, mainly including Frisingicoccus, Butyricicoccus, Eubacterium, Bacteroides, Dialister, Lachnoclostridium, Streptococcus, and Ruminococcus torques. Torularhodin inhibited the growth of pathogenic bacteria belonging to Enterobacteriaceae and transformed beneficial bacteria Bifidobacterium and Bacteroides into dominant bacteria under long-term dietary patterns. The functional analysis of the gut microbiota showed that differential genes were mainly enriched in glycolysis/gluconeogenesis and pentose phosphate pathways. The metabolome results also demonstrated that torularhodin mainly regulated fructose-1,6-bisphosphatase in the abovementioned pathway. Finally, the interaction network revealed that the gut microbiota (Bacteroides, Lachnospiraceae, and Megasphaera), metabolites (D-glucose, citric acid, tartaric acid, and propionic acid), and metabolic functions (pyruvate metabolism, glycolysis/gluconeogenesis, and pentose phosphate pathway) might be the key factors regulating the effect of torularhodin on the gut microbiota-metabolite-metabolism. Therefore, this study explored the mechanism of "torularhodin-gut microbiota-metabolite-metabolism" cross-feeding based on the bioinformatics methods, providing a theoretical basis for optimizing the gut microecology of a torularhodin-rich diet.

The combination of microbiome and metabolome to analyze the cross-cooperation mechanism of Echinacea purpurea polysaccharide with the gut microbiota in vitro and in vivo.

Echinacea purpurea polysaccharide (EPP) is a functional compound in Echinacea purpurea. At present, it is generally recognized that plant polysaccharides can regulate the intestinal microecology, but there are few studies on EPP. In this study, we used the digestive model (stomach-small intestine-colon) and a mouse model to study the effect of EPP on intestinal microecology and the mechanism. Also, combined with the microbiome and metabolome analysis methods, the interaction network mechanism of EPP-gut microbiota-metabolites-metabolism was investigated. After EPP was digested by human intestinal microbiota, the microbial diversity changed, with an increase in the relative abundance of Bifidobacterium and a decrease in the abundance of Prevotella, Catenibacterium and Ruminococcus torques. After metabolism in mice, the concentration of short-chain fatty acids increased, the abundances of Muribaculaceae and Alloprevotella increased, and those of Lachnospiraceae and Butyricicoccus decreased. Both in vivo and in vitro experiments revealed that EPP can downregulate the expression of 15 enzymes involved in porphyrin metabolism. In addition, the metabolome results also confirmed that alanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism are regulatory pathways of EPP. Tryptophan, ornithine, tyrosine, leucine, alanine and serine are hallmark metabolites. The cross-cooperation network greatly influenced the microbiota (Lactobacillus, Lachnospiraceae), metabolites (tryptophan, beta-D-fructose 1,6-bisphosphate), and metabolism (glycosphingolipid biosynthesis), suggesting that they may be the key factors mediating the metabolic function of EPP. Therefore, EPP has the effect of enhancing the proliferation of gut-beneficial bacteria that metabolize polysaccharides and produce valuable metabolites.

Improving food drying performance by cold plasma pretreatment: A systematic review.

Drying is an important and influential process to prolong the shelf-life of food in the food industry. Recent studies have shown that cold plasma (CP) as an emerging drying pretreatment technology can improve drying performance, reduce drying energy consumption, and improve dried food quality. This paper comprehensively reviewed the mechanism of CP improving drying performance, related equipment, energy consumption, influencing factors, and impact on drying quality. This review also discusses the advantages and disadvantages and proposes possible challenges and suggestions for future research. Most studies indicated that CP pretreatment could improve the drying rate and quality and reduce the drying energy consumption. CP can promote moisture diffusion and improve drying efficiency by etching the surface and affecting the internal microstructure. In addition, CP can enhance the quality of dried products by reducing drying time and enzyme activity. Further research is needed to explore the drying mechanisms and equipment innovations to promote the application of CP in the food drying industry.

Current status of microplastics and nanoplastics removal methods: Summary, comparison and prospect.

In modern society, plastics also play an indispensable role in people's lives due to their various excellent properties. However, when these plastic products are discarded after being used, after being subjected to external influences, they will continue to be worn, damaged and degraded into micro- and nano-scale plastics, which are microplastics and nanoplastics (M/NPs). Although people's attention has been paid to M/NPs at present, the focus is still mainly on the detection and hazard of M/NPs, and how to remove M/NPs is relatively less popular. This review was written in order to draw the attention of more researchers to remove M/NPs. This review first briefly introduces the research background of M/NPs, and also shows the main analytical methods currently used for qualitative and quantitative M/NPs. Then, most of the current literature on the removal of M/NPs was collected, and they were classified, summarized, and introduced according to the classification of physical, physicochemical, and biological methods. The advantages and disadvantages of various methods are summarized, and they are also compared, which can help more researchers choose the appropriate method for research. In addition, the application scenarios of these methods are briefly introduced. Finally, some future research directions are proposed for the current research status of M/NPs removal. It is hoped that this will further promote the development on the method of removing M/NPs.

Submicron-size polystyrene modulates amyloid fibril formation: From the perspective of protein corona.

At present, nanoplastics have been detected in food and the environment, but they have serious impacts on the human body. As one of the typical representatives of nanoplastics, polystyrene (PS) is generally used as an experimental object. Few studies found that PS could modulate the formation of amyloid fibrils, leading to the occurrence of diseases. However, its submicron-scale effects remain elusive. Thus, this study aimed to explore the interaction between PS of particle size 100-500 nm and hen egg-white lysozyme (HEWL). The results showed that PS of size 400 nm markedly promoted the primary nucleation step of amyloid fibril formation, and fibrils had more small fragments compared with PS of size 100 nm in the control and sample groups. PS of larger particle size changed the spatial structure of HEWL significantly. This study analyzed the experimental results from the perspective of protein corona and thermodynamics. The study confirmed that PS was able to form protein corona with HEWL in the initial stage, which was mainly driven by hydrophobic interactions. More importantly, the interface and junction of the protein corona were the main sites for the formation of amyloid fibrils. This study highlighted the role of submicron particle size and discussed the toxic effects of nanoparticles.

A natural fluorescent protein for ciprofloxacin sensing and mechanism study using molecular docking and circular dichroism.

Ciprofloxacin (CIP) is one of the common drug pollutants whose residues are often detected in the environment. In the current work, CIP was studied in aqueous environment based on a natural fluorescing compound called phycocyanin (PC). Using, a Spectro fluorophotometer, fluorescence detection of CIP was performed, and absorbance properties were studied using a UV-Visible spectrophotometer. In addition, a circular dichroism (CD) spectrophotometer and molecular docking analysis were implemented for further investigation. As the fluorometric measurement results showed, the fluorescence intensity of PC dropped linearly upon the addition of increasing amounts of CIP ranging from 0 to 120 µmol/L of final concentrations, with the limit of detection reaching down to 95 nM. In addition, the fluorescent sensor was found to be more selective towards CIP when tested against other six antibiotics and six pesticides. In the case of analysis of the PC-CIP interaction using a CD spectrophotometer the α-helix content of PC decreased in the presence of CIP, which is an indication of conformational changes in the secondary structure of PC. Moreover, the molecular docking analysis of the PC-CIP interaction assisted in locating the three sites where CIP binds with CIP, which in turn provided additional instances of the interaction mechanism between PC and CIP.

Microplastics contamination in eggs: Detection, occurrence and status.

Nowadays, the widespread distribution of microplastics (MPs) in various foods has received much attention. In this study, eggs were purchased as samples from local supermarkets to detect and analyze the presence of MPs. The digestion method was optimized for eggs to better isolate MPs, which proved MPs indeed exist in eggs, and the average content was 11.67 ± 3.98 particles/egg. The shape and size range of most MPs were spherical and 50-100 µm. The infrared results showed that the main type of MPs in eggs was polyethylene. The number of MPs in egg yolk was higher than that in egg white, and there was no significant change after cooking. In addition, the daily human intake of MPs was estimated. Therefore, the results of this study provided a background for the current status and pollution of MPs in eggs, and proposed the necessary control and preventive measures to avoid this situation.

Diethyl phosphate disrupts hypothalamus-pituitary-adrenal axis endocrine hormones via nuclear receptors GR and Nur77: Integration of evidences from in vivo, in vitro and in silico approaches.

Plenty of population epidemiology and cohort studies have found dialkyl phosphates (DAPs) in the urine were related to endocrine hormone disorders. However, we did not know whether these effects were caused by parent organophosphorus pesticides (OPs) or metabolite DAPs, especially the non-specific metabolite diethyl phosphate (DEP), which was the metabolic end product of most widely used diethyl OPs. In this study, animal experiments (in vivo), cell experiments (in vitro), small molecule-protein binding interaction experiments and computer molecular simulations (in silico) were used to explore the disturbing effects and molecular mechanisms of DEP on the hypothalamic-pituitary-adrenal (HPA) axis endocrine hormones. The animal experiments showed that chronic DEP exposure significantly disturbed the serum contents of HPA axis hormones in adult male rats. The target genes of glucocorticoid receptor (GR) in rat liver, including 11ß-hsd1 and Pepck1 and PEPCK protein expressions, were down-regulated. Moreover, the gluconeogenic abilities of rats were impaired. However, it did not affect the expression of GR in the rat hypothalamus. These results indicated that the physiological functions of glucocorticoids and GR were damaged. Furthermore, spectroscopy experiments, cell experiments, molecular docking and molecular dynamics simulations also suggested that DEP can bind to nuclear receptors GR and Nur77, affecting their transcription factor functions, and the transcriptional expression levels of their downstream target genes were reduced. The biosynthesis and secretion of adrenocorticotropic hormone and glucocorticoids were blocked. Therefore, DEP can inhibit the production and physiological functions of HPA axis endocrine hormones by disrupting these related proteins and antagonizing nuclear receptors. These results were considered to provide a theoretical basis for strictly controlling the residue limits of OPs and their metabolites in foods, agricultural products and the environment. They also revealed new targets for evaluating the toxicities and risks of pesticide metabolites.

Ultrasonic stimulation of milk fermentation: effects on degradation of pesticides and physiochemical, antioxidant, and flavor properties of yogurt.

BACKGROUND: Ultrasound has the potential to increase microbial metabolic activity, so this study explored the stimulatory effect of ultrasound pre-treatment on the degradation of four common pesticides (fenitrothion, chlorpyrifos, profenofos, and dimethoate) during milk fermentation by Lactobacillus plantarum and its effect on yogurt quality. RESULTS: Appropriate ultrasound pretreatment significantly enhanced the growth of L. plantarum. The degradation percentages of pesticides increased by 19-38% under ultrasound treatment. Ultrasonic intensity, pulse duty cycle, and duration time were key factors affecting microbial growth and pesticide degradation. Under optimal ultrasonic pre-treatment conditions, the degradation rate constants of four pesticides were at least 3.4 times higher than those without sonication. In addition, such ultrasound pretreatment significantly shortened yogurt fermentation time, increased the water holding capacity, hardness and antioxidant activity of the yogurt, and improved the flavor quality of the yogurt. CONCLUSION: Ultrasonic pretreatment significantly accelerated the degradation of the four pesticides during yogurt fermentation. In addition, such ultrasound pretreatment increased the efficiency of yogurt making and improved the quality of yogurt in terms of water holding capacity, firmness, antioxidant activity, and flavor. These findings provide a basis for the application of ultrasound to the removal of pesticide residues and quality improvement of yogurt. © 2022 Society of Chemical Industry.

Degradation mechanism and toxicity assessment of chlorpyrifos in milk by combined ultrasound and ultraviolet treatment.

The aim of this study was to compare the degradation kinetics of chlorpyrifos by treatment with ultrasound (US), ultraviolet radiation (UV) and a combination of both (US/UV), to evaluate the toxicity of the degradation products and the effect of the treatments on milk quality. US/UV markedly accelerated the degradation of chlorpyrifos. The half-life of chlorpyrifos by US/UV was 6.4 min, which was greatly shortened compared to the treatment with US or UV alone. Five degradation products were identified by GC-MS, and a degradation pathway for chlorpyrifos was proposed, based on density functional theory calculations. According to the luminescent bacteria test and predictions from a structure/activity relationship model, the toxicity of the degradation products was lower than that of chlorpyrifos. In addition, US/UV treatment had little effect on the quality of the treated milk. Therefore, US/UV can be used as a potential non-thermal processing method to degrade pesticide residues in milk.

In vitro and in silico approaches to investigate antimicrobial and biofilm removal efficacies of combined ultrasonic and mild thermal treatment against Pseudomonas fluorescens.

A combined ultrasonic and thermal (US-TM) treatment was developed in this study to achieve a high efficacy of P. fluorescens biofilm control. The present study demonstrated that combined a moderate ultrasound treatment (power ≥ 80 W) and a mild heat (up to 50 °C) largely destroyed biofilm structure in 15 min and removed>65.63% of biofilm from a glass slide where cultivated the P. fluorescens biofilm. Meanwhile, the viable cell count was decreased from 10.72 to 6.48 log10CUF/mL. Differences in biofilm removal and lethal modes of US-TM treatment were confirmed through microscopies analysis in vitro. The ultrasound first contributed to releasing the bacteria in the biofilm to the environment and simultaneously exposing inner bacteria at the deep layer of biofilm depending on shear force, shock waves, acoustic streaming, etc. When the biofilm structure was destroyed, US-TM treatment would synergistically inactivate P. fluorescens cells. In silico studies adopted COMSOL to simulate acoustic pressure and temperature distribution in the bioreactor; both of them were significantly influenced by various factors, such as input power, sonotrode position, materials and volume of container, etc. Facing the biofilm issue existing on the surface of container, boundary conditions were exported and thereby pointing out potential "dead ends" where the ultrasound may not be effectively transduced. Both in vitro and in silico results may inspire the food industry to adopt US-TM treatment to achieve biofilm control.

The combination of hexanal and geraniol in sublethal concentrations synergistically inhibits quorum sensing in Pseudomonas fluorescens-In vitro and in silico approaches.

AIM: Hexanal and geraniol are essential oil components with anti-quorum sensing (QS) activity against Pseudomonas fluorescens. This study demonstrated that QS inhibition (QSI) efficacy of the hexanal and geraniol combination (HG) was significantly higher when compared to those of their mono-counterparts at the same concentration. METHODS AND RESULTS: Tests on P. fluorescens motility, biofilm formation, acyl-homoserine lactones' (AHLs) production, gene expression in vitro, and molecular docking in silico were conducted to evaluate the synergistic effect of hexanal and geraniol on QSI. HG mixture at 0.5 minimal inhibitory concentration (MIC) showed a strong synergistic inhibition of biofilm formation (51.8%), motility (60.13%), and extracellular protease activity (58.9%) of P. fluorescens. The synthesis of AHLs, e.g., C8 -HSL and C12 -HSL, was inhibited by hexanal, geraniol, and HG; both AHLs are responsible for regulating virulence factors in P. fluorescens. The expression of pcoI and gacA genes regulating AHL synthetase and sensor kinase was significantly down-regulated by HG (0.29 and 0.38-fold) at 0.5 MIC. Hexanal and HG showed significant inhibition of the expression of pcoR and gacS genes, which are responsible for AHL receptor protein and response regulation; however, geraniol failed to downregulate the two genes. Molecular docking in silico also supported these findings. Hexanal, which gets inserted into the minor groove of pcoI/pcoR DNA fragments, inhibits the expression of both the genes. Both hexanal (-31.487 kcal/mol) and geraniol (-25.716 kcal/mol) had a higher binding affinity with PcoI protein than the halogenated furanone C30 (-24.829 kcal/mol), which is a known competitor of AHLs. Similarly, hexanal and geraniol strongly bind to the PcoR protein also. CONCLUSIONS: It was found that HG at 0.5 MIC could effectively inhibit QS by suppressing the expression of pcoR/gacS and gacA/gacS genes and therefore, could inhibit the motility and biofilm formation of P. fluorescens. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study indicated that HG at sub-MIC as QS inhibitor could be further developed as a new preservative of agri-food products.