Liquid crystal monomers disrupt photoreceptor patterning of zebrafish larvae via thyroid hormone signaling.

Liquid crystal monomers (LCMs) are the raw material for liquid crystal displays, and their use is steadily increasing in electronic products. Recently, LCMs have been reported to be novel endocrine disrupting chemicals, however, the mechanisms underlying their potential for thyroid hormone disruption and visual toxicity are not well understood. In this study, six widely used fluorinated LCMs (FLCMs) were selected to determine putative mechanisms underlying FLCM-induced toxicity to the zebrafish thyroid and visual systems. Exposure to FLCMs caused damage to retinal structures and reduced cell density of ganglion cell layer, inner nuclear layer, and photoreceptor layer approximately 12.6-46.1%. Exposure to FLCMs also disrupted thyroid hormone levels and perturbed the hypothalamic-pituitary-thyroid axis by affecting key enzymes and protein in zebrafish larvae. A thyroid hormone-dependent GH3 cell viability assay supported the hypothesis that FLCMs act as thyroid hormone disrupting chemicals. It was also determined that FLCMs containing aliphatic ring structures may have a higher potential for T3 antagonism compared to FLCMs without an aliphatic ring. Molecular docking in silico suggested that FLCMs may affect biological functions of thyroxine binding globulin, membrane receptor integrin, and thyroid receptor beta. Lastly, the visual motor response of zebrafish in red- and green-light was significantly inhibited following exposure to FLCMs. Taken together, we demonstrate that FLCMs can act as thyroid hormone disruptors to induce visual dysfunction in zebrafish via several molecular mechanisms.

Identification and validation of core microbes for the formation of the characteristic flavor of fermented oysters (Crassostrea gigas).

Self-fermented oyster homogenates were prepared to investigate core microbes and their correlations with flavor formation mechanisms. Five bacterial and four fungal genera were identified. Correlation analysis showed that Saccharomyces cerevisiae, Kazachstania, and L. pentosus were core species for the flavor of fermented products. Four core microbes were selected for inoculation into homogenates. Twelve key aroma compounds with odor activity values >1 were identified by gas chromatography-mass spectrometry. L. plantarum and S. cerevisiae were beneficial for producing key aroma compounds such as 1-octen-3-ol, (E,Z)-2,6-nonadienal, and heptanal. Fermentation with four microbes resulted in significant increases in contents of Asp, Glu, Lys, inosine monophosphate, and guanosine monophosphate, which provided freshness and sweetness. Fermentation with four microbes resulted in high digestibility, antioxidant abilities, and zinc contents. This study has elucidated the mechanism of flavor formation by microbial action and provides a reference for targeted flavor control in fermented oyster products.

Contribution of phospholipase B to the formation of characteristic flavor in steamed sturgeon meat.

Sensory analysis and untargeted lipidomics were employed to study the impact of phospholipase B (PLB) on lipid oxidation and flavor in steamed sturgeon meat, revealing the inherent relationship between lipid oxidation and flavor regulation. The research verified that PLB effectively suppresses fat oxidation and improves the overall taste of steamed sturgeon meat. Furthermore, the PLB group identified 52 compounds, and the content of odor substances such as isoamyl alcohol and hexanal was reduced compared with other groups. Finally, lipid substances containing eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) were screened out from 32 kinds of differential phospholipids. Through Pearson correlation analysis, it was observed that certain differential phospholipids such as PC (22:6) and PC (22:5) exhibited varying correlations with odor substances like hexanal and isovaleraldehyde. These findings suggest that PLB specifically affects certain phospholipids, leading to the production of distinct volatile substances through oxidative degradation.

Research progress of fishy odor in aquatic products: From substance identification, formation mechanism, to elimination pathway.

Fishy odor in aquatic products has a significant impact on the purchasing decisions of consumers. The production of aquatic products is a complex process involving culture, processing, transportation, and storage, which contribute to decreases in flavor and quality. This review systematically summarizes the fishy odor composition, identification methods, generation mechanism, and elimination methods of fishy odor compounds from their origin and formation to their elimination. Fishy odor compounds include aldehydes (hexanal, heptanal, and nonanal), alcohols (1-octen-3-ol), sulfur-containing compounds (dimethyl sulfide), and amines (trimethylamine). The mechanism of action of various factors affecting fishy odor is revealed, including environmental factors, enzymatic reactions, lipid oxidation, protein degradation, and microbial metabolism. Furthermore, the control and removal of fishy odor are briefly summarized and discussed, including masking, elimination, and conversion. This study provides a theoretical basis from source to elimination for achieving targeted regulation of the flavor of aquatic products, promoting industrial innovation and upgrading.

Correlation investigation between core microbe inoculation and the evolution of flavor characteristics during the storage of sturgeon caviar (Acipenser gueldenstaedtii).

The volatile and non-volatile compounds were monitored to investigate the microbial evolution associated with the characteristic flavors for sturgeon caviar during refrigeration. The results revealed that the composition of volatile compounds changed significantly with prolonged refrigeration time, especially hexanal, nonanal, phenylacetaldehyde, 3-methyl butyraldehyde, and 1-octen-3-ol. The nonvolatile metabolites were mainly represented by the increase of bitter amino acids (Thr. Ser, Gly, Ala, and Pro) and a decrease in polyunsaturated fatty acids, especially an 18.63 % decrease in 5 months of storage. A total of 332 differential metabolites were mainly involved in the biosynthetic metabolic pathways of α-linolenic acid, linoleic acid, and arachidonic acid. The precursors associated with flavor evolution were mainly phospholipids, including oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. The most abundant at the genus level was Serratia, followed by Arsenophnus, Rhodococcus, and Pseudomonas, as obtained by high-throughput sequencing. Furthermore, seven core microorganisms were isolated and characterized from refrigerated caviar. Among them, inoculation with Mammalian coccus and Bacillus chrysosporium restored the flavor profile of caviar and enhanced the content of nonvolatile precursors, contributing to the characteristic aroma attributes of sturgeon caviar. The study presents a theoretical basis for the exploitation of technologies for quality stabilization and control of sturgeon caviar during storage.

Study on antimicrobial activity of sturgeon skin mucus polypeptides (Rational Design, Self-Assembly and Application).

Despite the favorable biocompatibility of natural antimicrobial peptides (AMPs), their scarcity limits their practical application. Through rational design, the activity of AMPs can be enhanced to expand their application. In this study, we selected a natural sturgeon epidermal mucus peptide, AP-16 (APATPAAPALLPLWLL), as the model molecule and studied its conformational regulation and antimicrobial activity through amino acid substitutions and N-terminal lipidation. The structural and morphological transitions of the peptide self-assemblies were investigated using circular dichroism and transmission electron microscopy. Following amino acid substitution, the conformation of AL-16 (AKATKAAKALLKLWLL) did not change. Following N-terminal alkylation, the C8-AL-16 and C12-AL-16 conformations changed from random coil to ß-sheet or α-helix, and the self-assembly changed from nanofibers to nanospheres. AL-16, C8-AL-16, and C8-AL-16 presented significant antimicrobial activity against Pseudomonas and Shewanella at low concentrations. N-terminal alkylation effectively extended the shelf life of Litopenaeus vannamei. These results support the application of natural AMPs.

Acer truncatum Bunge seed oil ameliorated oxaliplatin-induced demyelination by improving mitochondrial dysfunction via the Pink1/Parkin mitophagy pathway.

Dietary nutritional support for special populations is an effective and feasible method to improve the quality of life of patients and reduce medical pressure. Acer truncatum Bunge seed oil (ATSO) is widely recognized for its ability to promote nerve myelin regeneration. To evaluate the ameliorative effects of ATSO on chemotherapy-induced demyelination, a zebrafish model of chemotherapy-induced demyelination was established. The results showed that 100 µg mL-1 of ATSO reversed tail morphology damage, axon degeneration, touch response delay, ROS level upregulation and the expression of myelin basic protein decrease in chemotherapy-induced zebrafish. In addition, the expression of myelin markers (including sox10, krox20, and pmp22) in oxaliplatin-induced cells was markedly reversed by ATSO and its active components (gondoic acid, erucic acid, and nervonic acid). ATSO and its active components could reverse demyelination by ameliorating mitochondrial dysfunction. Conversely, linoleic acid and linolenic acid promoted demyelination by exacerbating mitochondrial dysfunction. Moreover, the Pink1/Parkin pathway was recognized as the main reason for ATSO and its active components improving mitochondrial function by activating mitophagy and restoring autophagic flow. Taken together, this study demonstrated that ATSO and its active components could be further developed as novel functional food ingredients to antagonize demyelination.

In vivo and in silico toxicity assessment of four common liquid crystal monomers to Daphnia magna: Novel endocrine disrupting chemicals in crustaceans?

Liquid crystal monomers (LCMs) are widely used in liquid crystal displays (LCDs) and are proposed to be a new generation of environmentally persistent, bioaccumulative and toxic (PBT) substances that are increasingly detected in rivers and seas. However, there is a lack of in vivo data that characterize adverse responses and toxic mechanisms of LCMs on aquatic organisms. The aim of this study was to comprehensively investigate the effect of four typical LCMs on the lethality, growth, molting, and reproductive capacity of Daphnia magna (D. magna), a highly studied aquatic species in environmental toxicology. Whole body and enzymatic biomarkers (i.e., body length, chitobiase, acetylcholinesterase, antioxidant defense) were measured to assess the toxicity of LCMs. The 48 h mortality rate and observations of disrupted thorax development and inhibition of ecdysis indicate that D. magna are sensitive to LCMs exposure. Oxidative stress, impaired neurotransmission, and disruptions in molting were observed in short-term biomarker tests using LCMs. A 21 day exposure of D. magna to LCMs resulted in reduced growth, reproduction, and population intrinsic growth rate. In addition, chitobiase and 20-hydroxyecdysone, enzymes important for the molting process, were altered at 7, 14 and 21 d. This is hypothesized to be related to endocrine imbalance resulting from LCM exposure. Based on molecular docking simulations, there is evidence that LCMs bind directly to ecdysteroid receptors; this may explain the observed endocrine disrupting effects of LCMs. These data support the hypothesis that LCMs are endocrine disrupting chemicals in aquatic species, impacting the process of molting. This may subsequently lead to lower reproduction and unbalanced population dynamics.

Effects of Sous-Vide on Quality, Structure and Flavor Characteristics of Tilapia Fillets.

To investigate the effects of traditional high-temperature cooking and sous-vide cooking on the quality of tilapia fillets, muscle microstructure, texture, lipid oxidation, protein structure, and volatile compounds were analyzed. In comparison with samples subjected to traditional high-temperature cooking, sous-vide-treated samples exhibited less protein denaturation, a secondary structure dominated by α-helices, a stable and compact structure, a significantly higher moisture content, and fewer gaps in muscle fibers. The hardness of the sous-vide-treated samples was higher than that of control samples, and the extent of lipid oxidation was significantly reduced. The sous-vide cooking technique resulted in notable changes in the composition and relative content of volatile compounds, notably leading to an increase in the presence of 1-octen-3-ol, α-pinene, and dimethyl sulfide, and a decrease in the levels of hexanal, D-limonene, and methanethiol. Sous-vide treatment significantly enhanced the structural stability, hardness, and springiness of muscle fibers in tilapia fillets and reduced nutrient loss, enriched flavor, and mitigated effects on taste and fishy odor.

Identification and Verification of Novel Umami Peptides Isolated from Hybrid Sturgeon Meat (Acipenser baerii × Acipenser schrenckii).

To explore the umami mechanism in sturgeon meat, five peptides (ERRY, VRGPR, LKYPLE, VKKVFK, and YVVFKD) were isolated and identified by ultrafiltration, gel filtration chromatography, and UPLC-QTOF-MS/MS. The omission test confirmed that the five umami peptides contributed to the umami taste of sturgeon meat. Also, the peptides had the double effective role of enhancing both umami and saltiness. The threshold of ERRY was only 0.031, which exceeded most umami peptides in the last 3 years. Molecular docking results showed that five peptides could easily bind to Gly167, Ser170, and Try218 residues in T1R3 through hydrogen bonds and electrostatic interactions. Furthermore, molecular dynamics simulations indicated that hydrogen bonds and hydrophobic interactions were the main intermolecular interaction forces. This study could contribute to revealing the umami taste mechanism of sturgeon meat and provide new insights for effective screening of short umami peptides.

Prevalence and Risk Factors of Mitral, Tricuspid, and Aortic Regurgitation: A Population-Based Study from Rural Northeast China.

The population-based studies on the epidemiologic features of valvular regurgitation in Northeast China are scarce. We aim to estimate the prevalence and risk factors of mitral regurgitation (MR), tricuspid regurgitation (TR), and aortic regurgitation (AR) in a general population from rural Northeast China. Valvular regurgitation was assessed by color flow Doppler echocardiography in a population-based survey of 11,278 participants aged ≥35 years in rural areas of Liaoning Province during 2012 to 2013. The prevalence of mild or greater MR and TR were 1.6% and 1.5%, respectively. Trace or greater AR was present in 4.1% of the participants. In the multivariable regression model, older age, left atrial dimension, low left ventricular (LV) ejection fraction, and fasting plasma glucose were associated with higher risk of MR in men, whereas only older age and left atrial dimension increased the risk in women. Body mass index was found to be a protective factor for MR in women (odds ratio 0.847, 95% confidence interval 0.741 to 0.969). TR was independently associated with age, heart rate, low LV ejection fraction, current drinking status, and high-density lipoprotein cholesterol. The risk for AR significantly increased with age in both genders. LV mass index and aortic dimension increased the risk of AR in males, and females with higher LV mass index and high-density lipoprotein cholesterol had an increased risk for AR. In both genders, systolic blood pressure presented as a risk factor for AR, while diastolic blood pressure as a protective factor. In this large Chinese population-based study, we found remarkably low prevalence of valvular regurgitation, adding evidence for estimating disease burden and making policy strategies in Northeast China.

α-myosin heavy chain lactylation maintains sarcomeric structure and function and alleviates the development of heart failure.

The sarcomeric interaction of α-myosin heavy chain (α-MHC) with Titin is vital for cardiac structure and contraction. However, the mechanism regulating this interaction in normal and failing hearts remains unknown. Lactate is a crucial energy substrate of the heart. Here, we identify that α-MHC undergoes lactylation on lysine 1897 to regulate the interaction of α-MHC with Titin. We observed a reduction of α-MHC K1897 lactylation in mice and patients with heart failure. Loss of K1897 lactylation in α-MHC K1897R knock-in mice reduces α-MHC-Titin interaction and leads to impaired cardiac structure and function. Furthermore, we identified that p300 and Sirtuin 1 act as the acyltransferase and delactylase of α-MHC, respectively. Decreasing lactate production by chemical or genetic manipulation reduces α-MHC lactylation, impairs α-MHC-Titin interaction and worsens heart failure. By contrast, upregulation of the lactate concentration by administering sodium lactate or inhibiting the pivotal lactate transporter in cardiomyocytes can promote α-MHC K1897 lactylation and α-MHC-Titin interaction, thereby alleviating heart failure. In conclusion, α-MHC lactylation is dynamically regulated and an important determinant of overall cardiac structure and function. Excessive lactate efflux and consumption by cardiomyocytes may decrease the intracellular lactate level, which is the main cause of reduced α-MHC K1897 lactylation during myocardial injury. Our study reveals that cardiac metabolism directly modulates the sarcomeric structure and function through lactate-dependent modification of α-MHC.

Photochemical behavior and photo-induced toxicity of chiral pesticides and their chiral monomers in aqueous environment.

The photochemical behaviors of chiral pollutants in aqueous solutions are rarely studied using chiral monomers, which may hamper their precise risk assessment and lead to suspicious conclusions. In this study, we systematically investigated the phototransformation behavior and toxicity evolution of two widely used chiral pesticides (triadimefon (TF) and triadimenol (TN)) at enantiomer and diastereomer levels, and proposed a calculation method of total photolysis rate constants of chiral mixture. Results show that TF and TN could be photodegraded faster in pure water than in natural waters, and the observed photolysis rate constants (kobs) of TN with two chiral centers exhibit enantioselectivity, i.e., kobs(TN-RS) = kobs(TN-SR) > kobs(TN-RR) = kobs(TN-SS). The photolysis of TF and TN mainly occurs through their excited singlet and triplet states, respectively. Their photodegradation pathways mainly include dechlorination and elimination of triazole ring. TF could also undergo ether bond cleavage. It is also found that, both TF and TN exhibit photo-induced toxicity to V. fischeri, due to the generation of more toxic products than parent compounds. Furthermore, TN exhibits enantioselective photo-induced toxicity after 240-min irradiation, which could be ascribed to the formation of chiral products. These results could benefit the understanding of enantioselective environmental behavior of chiral pollutants.

Down-regulation of WWP2 aggravates Type 2 diabetes mellitus-induced vascular endothelial injury through modulating ubiquitination and degradation of DDX3X.

BACKGROUND: Endothelial injury caused by Type 2 diabetes mellitus (T2DM) is considered as a mainstay in the pathophysiology of diabetic vascular complications (DVCs). However, the molecular mechanism of T2DM-induced endothelial injury remains largely unknown. Here, we found that endothelial WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) act as a novel regulator for T2DM-induced vascular endothelial injury through modulating ubiquitination and degradation of DEAD-box helicase 3 X-linked (DDX3X). METHODS: Single-cell transcriptome analysis was used to evaluate WWP2 expression in vascular endothelial cells of T2DM patients and healthy controls. Endothelial-specific Wwp2 knockout mice were used to investigate the effect of WWP2 on T2DM-induced vascular endothelial injury. In vitro loss- and gain-of-function studies were performed to assess the function of WWP2 on cell proliferation and apoptosis of human umbilical vein endothelial cells. The substrate protein of WWP2 was verified using mass spectrometry, coimmunoprecipitation assays and immunofluorescence assays. The mechanism of WWP2 regulation on substrate protein was investigated by pulse-chase assay and ubiquitination assay. RESULTS: The expression of WWP2 was significantly down-regulated in vascular endothelial cells during T2DM. Endothelial-specific Wwp2 knockout in mice significantly aggravated T2DM-induced vascular endothelial injury and vascular remodeling after endothelial injury. Our in vitro experiments showed that WWP2 protected against endothelial injury by promoting cell proliferation and inhibiting apoptosis in ECs. Mechanically, we found that WWP2 is down-regulated in high glucose and palmitic acid (HG/PA)-induced ECs due to c-Jun N-terminal kinase (JNK) activation, and uncovered that WWP2 suppresses HG/PA-induced endothelial injury by catalyzing K63-linked polyubiquitination of DDX3X and targeting it for proteasomal degradation. CONCLUSION: Our studies revealed the key role of endothelial WWP2 and the fundamental importance of the JNK-WWP2-DDX3X regulatory axis in T2DM-induced vascular endothelial injury, suggesting that WWP2 may serve as a new therapeutic target for DVCs.

Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases.

Post-translational modifications regulate numerous biochemical reactions and functions through covalent attachment to proteins. Phosphorylation, acetylation and ubiquitination account for over 90% of all reported post-translational modifications. As one of the tyrosine protein kinases, spleen tyrosine kinase (SYK) plays crucial roles in many pathophysiological processes and affects the pathogenesis and progression of various diseases. SYK is expressed in tissues outside the hematopoietic system, especially the heart, and is involved in the progression of various cardio-cerebrovascular diseases, such as atherosclerosis, heart failure, diabetic cardiomyopathy, stroke and others. Knowledge on the role of SYK in the progress of cardio-cerebrovascular diseases is accumulating, and many related mechanisms have been discovered and validated. This review summarizes the role of SYK in the progression of various cardio-cerebrovascular diseases, and aims to provide a theoretical basis for future experimental and clinical research targeting SYK as a therapeutic option for these diseases.

Photolysis mechanism of eleven insecticides under simulated sunlight irradiation: Kinetics, pathway and QSAR.

Insecticides are widely used in crop protection against insects and frequently detected in aquatic environment. Photolysis kinetics are directly related with exposure assessment and risk assessment. However, the photolysis mechanism of neonicotinoid insecticides with different structures has not been studied and compared systematically in the literature. In this paper, the photolysis rate constants in water were determined for eleven insecticides under irradiation of simulated sunlight. At the same time, the photolysis mechanism and effect of dissolved organic matter (DOM) on their photolysis were studied. The results showed that photolysis rates of eleven insecticides vary in a large range. The photolysis rates of nitro-substituted neonicotinoids and butenolide insecticide are much faster than that of cyanoimino-substituted neonicotinoids and sulfoximine insecticide. The ROS scavenging activity assays reveal that direct photolysis dominates the degradation of seven insecticides and, on the other hand, self-sensitized photolysis dominates four insecticides. The shading-effect from DOM can reduce the direct photolysis rates, on the other hand, ROSs generated by triplet-state DOM (3DOM*) can also accelerate photolysis of insecticides. According to the photolytic products identified from HPLC-MS, these eleven insecticides have different photolysis pathways. Six insecticides are degraded from the removal of nitro group from their parent compounds and four insecticides are degraded through ·OH reaction or singlet oxygen (1O2) reaction. QSAR (quantitative structure-activity relationship) analysis showed that photolysis rate was directly related to the energy gap between the highest occupied molecular orbital to the lowest unfilled molecular orbital (Egap = ELUMO-EHOMO) and dipole moment (δ). These two descriptors reflect the chemical stability and reactivity of insecticides. The pathways developed from identified products and the molecular descriptors of QSAR models can well verify the photolysis mechanisms of eleven insecticides.

Predictive value of liver fibrosis scores in cardiovascular diseases among hypertensive population.

PURPOSE: To explore the predictive value of liver fibrosis scores [fibrosis-4, AST/platelet ratio index, BAAT score (BMI Age ALT TG), and BARD score (BMI AST/ALT Ratio Diabetes)] for the risk of cardiovascular disease (CVD) in a hypertensive population. METHODS: A total of 4164 hypertensive participants without history of CVD were enrolled in the follow-up. Four liver fibrosis scores (LFSs) were used, including the fibrosis-4 (FIB-4), APRI, BAAT score, and BARD score. The endpoint was CVD incidence which was defined as stroke or coronary heart disease (CHD) during the follow-up period. Cox regression analyses were used to calculate hazard ratios between LFSs and CVD. Kaplan-Meier curve was used to show the probability of CVD in different levels of LFSs. Restricted cubic spline further explored whether the relationship between LFSs and CVD was linear. Finally, we assessed the discriminatory ability of each LFS for CVD was assessed using C -statistics, net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS: During a median follow-up time of 4.66 years, 282 hypertensive participants had CVD. Kaplan-Meier curve showed that four LFSs were associated with CVD and high levels of LFSs significantly increase the probability of CVD in hypertensive population. In the multivariate Cox regression analysis, the adjusted hazard ratios for four LFSs were 3.13 in FIB-4, 1.66 in APRI, 1.47 in BAAT score, and 1.36 in BARD score. Moreover, after adding LFSs to original risk prediction model, we find that all four new models have higher C -statistics of CVD than the traditional model. Furthermore, the results of both NRI and IDI were positive, indicating that LFSs enhanced the effect on the prediction of CVD. CONCLUSIONS: Our study showed that LFSs were associated with CVD in hypertensive populations in northeastern China. Furthermore, it suggested that LFSs could be a new tool for identifying patients at high risk of primary CVD in a hypertensive population.

Metabolomics investigation on the volatile and non-volatile composition in enzymatic hydrolysates of Pacific oyster (Crassostrea gigas).

To investigate the differences of volatile and non-volatile metabolites between oyster enzymatic hydrolysates and boiling concentrates, molecular sensory analysis and untargeted metabolomics were employed. "Grassy," "fruity," "oily/fatty," "fishy," and "metallic" were identified as sensory attributes used to evaluate different processed oyster homogenates. Sixty-nine and 42 volatiles were identified by gas chromatography-ion mobility spectrometry and gas chromatography-mass spectrometry, respectively. Pentanal, 1-penten-3-ol, hexanal, (E)-2-pentenal, heptanal, (E)-2-hexenal, 4-octanone, (E)-4-heptenal, 3-octanone, octanal, nonanal, 1-octen-3-ol, benzaldehyde, (E)-2-nonenal, and (E, Z)-2,6-nonadienal were detected as the key odorants (OAV > 1) after enzymatic hydrolysis. Hexanal, (E)-4-heptenal, and (E)-2-pentenal were significantly associated with off-odor, and 177 differential metabolites were classified. Aspartate, glutamine, alanine, and arginine were the key precursors affecting the flavor profile. Linking sensory descriptors to volatile and nonvolatile components of different processed oyster homogenates will provide information for the process and quality improvement of oyster products.

Repurposing Axl Kinase Inhibitors for the Treatment of Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) infection persists as a common pathogen of pulmonary infection in infants and in the elderly with high morbidity and mortality. However, no specific therapeutics are available. Axl, a member of the TAM (Tyro3, Axl, and Mertk) family receptor kinases, is a pleiotropic inhibitor of the innate immune response and functions as a negative regulator of interferon pathway activation. In this report, we investigated Axl inhibitors for their effects against RSV infection. Axl inhibition with kinase inhibitors, including BMS-777607, R428, and TP-0903, or Axl ablation resulted in a significant reduction of RSV infection in cell-based assays. In an animal model of pulmonary RSV infection, treatment with BMS-777607, R428, or TP-0903 ameliorated pulmonary pathology with a significant reduction of RSV titers in the lung tissues and, consequently, decreased the expression of proinflammatory genes. The host promotes ISG expression for the antiviral response and for viral clearance. We found that Axl inhibition led to more robust IFN-ß expression and antiviral gene induction. Thus, the results of this study imply that Axl kinase inhibitors may possess a broad spectrum of antiviral effects by promoting ISG expression.