Correlation of CT features of lung adenocarcinoma with sex and age.

This study aimed to retrospectively examine the computed tomography (CT) features of lung adenocarcinoma across different demographic groups. Preoperative chest CT findings from 1266 surgically resected lung adenocarcinoma cases were retrospectively analyzed. Lung adenocarcinomas were categorized based on CT characteristics into pure ground glass (pGGO), nodule-containing ground glass opacity (mGGO), and pure solid without containing ground glass opacity (pSD). These categories were correlated with sex, age, EGFR status, and five histopathological subtypes. The diameters of pGGO, mGGO, and pSD significantly increased across all patient groups (P < 0.05). Males exhibited a significantly higher proportion of pSD than females (P = 0.002). The mean diameters of pGGO and pSD were significantly larger in males than in females (P = 0.0017 and P = 0.043, respectively). The frequency of pGGO was higher in the younger age group (≤ 60 years) compared to the older group (> 60 years) for both males (P = 0.002) and females (P = 0.027). The frequency of pSD was higher in the older age group for both sexes. A linear correlation between age and diameter was observed in the entire cohort as well as in the male and female groups (P < 0.0001 for all groups). EGFR mutations were less frequent in pSD compared to pGGO (P = 0.0002) and mGGO (P < 0.0001). The frequency of lesions containing micropapillary components increased from pGGO to mGGO and pSD (P < 0.0001 for all). The frequency of lesions containing solid components also increased from pGGO to mGGO and pSD (P = 0.045, P < 0.0001, and P < 0.0001, respectively). The CT features of lung adenocarcinoma exhibit differences across genders and age groups. Male gender and older age are risk factors for lung adenocarcinoma growth.

Factors correlating the expression of PD-L1.

OBJECTIVE: PD-L1 was an important biomarker in lung adenocarcinoma. The study was to confirm the most important factor affecting the expression of PD-L1 remains undetermined. METHODS: The clinical records of 1045 lung adenocarcinoma patients were retrospectively reviewed. The High-Resolution Computed Tomography (HRCT) scanning images of all the participants were analyzed, and based on the CT characteristics, the adenocarcinomas were categorized according to CT textures. Furthermore, PD-L1 expression and Ki67 index were detected by immunohistochemistry. All patients underwent EGFR mutation detection. RESULTS: Multivariate logistic regression analysis revealed that smoking (OR: 1.73, 95% CI: 1.04-2.89, p = 0.004), EGFR wild (OR: 1.52, 95% CI: 1.11-2.07, p = 0.009), micropapillary subtypes (OR: 2.05, 95% CI: 1.46-2.89, p < 0.0001), and high expression of Ki67 (OR: 2.02, 95% CI: 1.44-2.82, p < 0.0001) were independent factors which influence PD-L1 expression. In univariate analysis, tumor size > 3 cm and CT textures of pSD showed a correlation with high expression of PD-L1. Further analysis revealed that smoking, micropapillary subtype, and EGFR wild type were also associated with high Ki67 expression. Moreover, high Ki67 expression was observed more frequently in tumors of size > 3 cm than in tumors with ≤ 3 cm size as well as in CT texture of pSD than lesions with GGO components. In addition, multivariate logistic regression analysis revealed that only lesions with micropapillary components correlated with pSD (OR: 3.96, 95% CI: 2.52-5.37, p < 0.0001). CONCLUSION: This study revealed that in lung adenocarcinoma high Ki67 expression significantly influenced PD-L1 expression, an important biomarker for immune checkpoint treatment.

Smartphone-assisted colorimetric biosensor for the determination of organophosphorus pesticides on the peel of fruits.

Nowadays, the widespread use of organophosphorus pesticides (OPs) in agricultural production leads to varying degrees of residues in crops, which pose a potential threat to human health. Conventional methods used in national standard for the detection of OPs in fruits and vegetables require expensive instruments or cumbersome sample pretreatment steps for the analysis. To address these challenges, in this work, we took advantage of the peroxidase-like activity of PtCu3 alloy nanocrystals (NCs) for a colorimetric and smartphone assisted sensitive detection of OPs. With the assist of a smartphone, the concentration of OPs on the peel of fruits could be obtained by comparing the B/RG value (the brightness value of blue divided by those of red and green) of a test strip with a calibration curve. This work not only provides a facile and cost-effective method to detect pesticides but also makes a positive contribution to food safety warning.

Preservation effects of photodynamic inactivation-mediated antibacterial film on storage quality of salmon fillets: Insights into protein quality.

The preservation effects of a photodynamic inactivation (PDI)-mediated polylactic acid/5-aminolevulinic acid (PLA/ALA) film on the storage quality of salmon fillets were investigated. Results showed that the PDI-mediated PLA/ALA film could continuously generate reactive oxygen species by consuming oxygen to inactivate native pathogens and spoilage bacteria on salmon fillets. Meanwhile, the film maintained the content of muscle proteins and their secondary and tertiary structures, as well as the integrity of myosin by keeping the activity of Ca2+-ATPase, all of which protected the muscle proteins from degradation. Furthermore, the film retained the activity of total superoxide dismutase (T-SOD), suppressed the accumulation of lipid peroxides (e.g., MDA), which greatly inhibited four main types of protein oxidations. As a result, the content of flavor amino acids and essential amino acids in salmon fillets was preserved. Therefore, the PDI-mediated antimicrobial packaging film greatly preserves the storage quality of aquatic products by preserving the protein quality.

Identification and Characterization of Retinitis Pigmentosa in a Novel Mouse Model Caused by PDE6B-T592I.

The cGMP-phosphodiesterase 6 beta subunit (PDE6B) is an essential component in the phototransduction pathway for light responses in photoreceptor cells. PDE6B gene mutations cause the death of rod photoreceptors, named as hereditary retinitis pigmentosa (RP) in humans and retinal degeneration (RD) in rodents. Here, we report a new RD model, identified from a phenotypic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice, which displays retinal degeneration caused by a point mutation in the Pde6b gene that results in PDE6B-T592I mutant protein. The homozygous mutant mice show an extensive loss of rod photoreceptors at the age of 3 weeks; unexpectedly, the loss of rod photoreceptors can be partly rescued by dark rearing. Thus, this RD mutant model displays a light-dependent loss of rod photoreceptors. Both western blot and immunostaining results show very low level of mutant PDE6B-T592I protein in the retina. Structure modeling suggests that the T592I mutation probably affects the function and stability of PDE6B protein by changing intramolecular interactions. We further demonstrate that the expression of wild-type PDE6B delivered by subretinally injected adeno-associated virus (rAAV) prevents photoreceptor cell death in this RD model in vivo. The PDE6B-T592I mutant is, therefore, a valuable RD model for evaluating rAAV-mediated treatment and for investigating the molecular mechanism of light-dependent rod photoreceptor cell death that is related to impaired PDE6B function.

Aggregation-induced enhancement of peroxidase-mimetic activity of DNAzyme-gold nanoparticles for ultrasensitive detection of lead ions.

Lead ion (Pb2+) detection is critically important in environmental protection and health management. In this work, we developed a simple signal-enhanced colorimetric sensor for the detection of Pb2+ based on the peroxidase-mimetic property of gold nanoparticles (AuNPs). When a certain concentration of Pb2+ was added to a solution of DNAzyme-modified AuNPs, aggregation was triggered, and the result was an enhancement of the peroxidase-mimetic activity of AuNPs. Then, the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB) by the catalyst of AuNPs was used for the sensitive UV-Vis and colorimetric detection of Pb2+. When a higher concentration of Pb2+ was added, the greater amount of aggregation of AuNPs resulted in the enhancement of the UV-Vis adsorption of the solution at 652 nm, with a deepening of the blue color of the solution. After optimization of the experimental conditions, a linear relationship between the absorbance of oxidized TMB at 652 nm and the logarithm of Pb2+ concentration was obtained, which had been divided into two parts (25 pM to 2.5 µM, and 2.5 µM to 250 µM). The detection limit was as low as 10 pM. The satisfactory specificity and rapid response of the sensor showed that it has promising application for the detection of Pb2+ in real samples.

The two-component system expression patterns and immune regulatory mechanism of Vibrio parahaemolyticus with different genotypes at the early stage of infection in THP-1 cells.

Vibrio parahaemolyticus must endure various challenging circumstances while being swallowed by phagocytes of the innate immune system. Moreover, bacteria should recognize and react to environmental signals quickly in host cells. Two-component system (TCS) is an important way for bacteria to perceive external environmental signals and transmit them to the interior to trigger the associated regulatory mechanism. However, the regulatory function of V. parahaemolyticus TCS in innate immune cells is unclear. Here, the expression patterns of TCS in V. parahaemolyticus-infected THP-1 cell-derived macrophages at the early stage were studied for the first time. Based on protein-protein interaction network analysis, we mined and analyzed seven critical TCS genes with excellent research value in the V. parahaemolyticus regulating macrophages, as shown below. VP1503, VP1502, VPA0021, and VPA0182 could regulate the ATP-binding-cassette (ABC) transport system. VP1735, uvrY, and peuR might interact with thermostable hemolysin proteins, DNA cleavage-related proteins, and TonB-dependent siderophore enterobactin receptor, respectively, which may assist V. parahaemolyticus in infected macrophages. Subsequently, the potential immune escape pathways of V. parahaemolyticus regulating macrophages were explored by RNA-seq. The results showed that V. parahaemolyticus might infect macrophages by controlling apoptosis, actin cytoskeleton, and cytokines. In addition, we found that the TCS (peuS/R) could enhance the toxicity of V. parahaemolyticus to macrophages and might contribute to the activation of macrophage apoptosis. IMPORTANCE This study could offer crucial new insights into the pathogenicity of V. parahaemolyticus without tdh and trh genes. In addition, we also provided a novel direction of inquiry into the pathogenic mechanism of V. parahaemolyticus and suggested several TCS key genes that may assist V. parahaemolyticus in innate immune regulation and interaction.

Effect of low temperature on the resistance of Listeria monocytogenes and Escherichia coli O157:H7 to acid electrolyzed water.

Low temperature can affect the resistance of pathogenic bacteria to other external stress. The present study was envisaged to assess the tolerance of L. monocytogenes and E. coli O157:H7 to acidic electrolyzed water (AEW) under low temperature stress. AEW treatment caused a damage to cell membrane of the pathogenic bacteria, which led to protein leakage and DNA damage. Compared with the pathogenic bacteria cultured at 37 °C (pure culture), the L. monocytogenes and E. coli O157:H7 cells cultivated at low temperature presented a less damage and had a higher survival rate when exposed to AEW. Therefore, 4 °C or 10 °C grown bacteria were less susceptible to AEW than those cultured at 37 °C. And this phenomenon was verified when AEW was used to treat the pathogenic bacteria inoculated in salmon. In addition, transcriptomic sequencing technology (RNA-seq) was used to reveal the mechanism of AEW tolerance of L. monocytogenes under low temperature stress. Transcriptomic analysis showed the expression of the cold shock protein, regulation of DNA-templated transcription, ribosome pathway, phosphotransferase system (PTS), bacteria chemotaxis, SOS response and DNA repair were involved in the resistance of L. monocytogenes to AEW. We speculated that the direct modulation of the expression of cold shock protein CspD, the indirect effect on the expression of cspD by inhibiting the expression of Crp/Fnr family transcriptional regulator or enhancing the level of cAMP by regulating PTS could reduce the resistance of L. monocytogenes cultivated at 4 °C to AEW. Our study contributes to solving the problem of the reduced bacteriostatic effect in cold storage environment.

Expression patterns and influence of the two-component system in Vibrio parahaemolyticus of different genotypes.

Vibrio parahaemolyticus is a foodborne pathogen that threatens global food security and human health. The two-component system (TCS) is a primary method for bacteria self-regulate and adapt to the environment. Previous studies have shown that V. parahaemolyticus has four hemolytic genotypes with diverse biological phenotypes and environmental adaptability, but the mechanism is unclear. In this study, we investigated TCS expression patterns in V. parahaemolyticus with different genotypes for the first time and explored the differences in TCS between strains. The results showed similarities in the TCS expression pattern between VPC17 (tdh+/trh-) and VPC44 (tdh-/trh-), while VPC85(tdh-/trh+) had the least similar TCS expression pattern to the other three strains. Analysis of biological information revealed that different regulations of C4 dicarboxylate transport, tetrathionate uptake, antibiotic resistance, and flagellar synthesis involved in the TCS might influence strains' growth, antibiotic resistance, biofilm, and virulence. The different TCS regulatory abilities of strains might be one of the reasons for diverse biological characteristics and different environmental adaptations. This work provides a theoretical basis and a new research direction for the strain variability of V. parahaemolyticus.

Hierarchical Flower-like WO3 Nanospheres Decorated with Bimetallic Au and Pd for Highly Sensitive and Selective Detection of 3-Hydroxy-2-butanone Biomarker.

Listeria monocytogenes, which is abundant in environment, can lead to many kinds of serious illnesses and even death. Nowadays, indirectly detecting the metabolite biomarker of L. monocytogenes, 3-hydroxy-2-butanone, has been verified to be an effective way to evaluate the contamination of L. monocytogenes. However, this detection approach is still limited by sensitivity, selectivity, and ppb-level detection limit. Herein, low-cost and highly sensitive and selective 3-hydroxy-2-butanone sensors have been proposed based on the bimetallic AuPd decorated hierarchical flower-like WO3 nanospheres. Notably, the 1.0 wt % AuPd-WO3 based sensors displayed the highest sensitivity (Ra/Rg = 84 @ 1 ppm) at 250 °C. In addition, the sensors showed outstanding selectivity, rapid response/recovery (8/4 s @ 10 ppm), and low detection limit (100 ppb). Furthermore, the evaluation of L. monocytogenes with high sensitivity and specificity has been achieved using 1.0 wt % AuPd-WO3 based sensors. Such a marvelous sensing performance benefits from the synergistic effect of bimetallic AuPd nanoparticles, which lead to thicker electron depletion layer and increased adsorbed oxygen species. Meanwhile, the unique hierarchical nanostructure of the flower-like WO3 nanospheres benefits the gas-sensing performance. The AuPd-WO3 nanosphere-based sensors exhibit a particular and highly selective method to detect 3-hydroxy-2-butanone, foreseeing a feasible route for the rapid and nondestructive evaluation of foodborne pathogens.

Antibacterial activity of essential oils extracted from the unique Chinese spices cassia bark, bay fruits and cloves.

Spices are widely used in daily life such as diet and have certain activity. Especially in China, spices have been mainly used as condiments for thousands of years in order to improve the sensory quality of food; in addition, they and their derivatives can also be used as preservatives. In this study, three spices with unique Chinese characteristics widely used were selected: cassia bark (bark of Cinnamomum camphora Presl), bay fruits (Laurus nobilis), and cloves (Syzygiumaromaticum). The main components and antibacterial ability of these three spices were analyzed by simulated extraction method. Through headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) analysis, it was determined that the main active compounds in the essential oils of cassia bark, bay fruits and cloves were cinnamaldehyde (78.11%), cinnamaldehyde (61.78%) and eugenol (75.23%), respectively. The agar plate diffusion test and the simulated food culture medium experiment confirmed that the essential oils extracted from the three flavors have antibacterial effects on Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Listeria ivanovii, Listeria grayi and Vibrio parahaemolyticus. The antibacterial activity of different strains has different optimal extraction conditions. Generally speaking, cinnamon essential oil has the strongest antibacterial activity, while laurel fruit has the lowest antibacterial activity. The study proved the antibacterial activity of these three Chinese-specific spices and provided some new ideas and methods for the subsequent research and preparation of natural food additives and food antibacterial agents.

Icariin attenuates the tumor growth by targeting miR-1-3p/TNKS2/Wnt/ß-catenin signaling axis in ovarian cancer.

Purpose: Despite various therapy advances, ovarian cancer remains an incurable disease for which survival rates have only modestly improved. Natural products are important sources of anti-cancer lead compounds. Icariin exhibited broad anti-cancer efficacy. However, the mechanism of icariin against ovarian cancer is poorly elucidated. Methods: Cell viability was detected to evaluate the effect of icariin on SKOV-3 cells. The cell cycle and apoptosis were analyzed. The transcript of SKOV-3 cells was profiled by RNA-seq. GSEA and DEGs analyses were performed to interpret gene expression data. Western blot and TOP/FOP flash assay were applied to detect Wnt/ß-catenin signaling. MiRDB database and dual-luciferase reporter assay was applied to study the regulation of miR-1-3p on TNKS2. Anti-tumor efficacy of icariin was evaluated by xenograft mouse model. Immunohistochemistry was performed with antibodies against Ki67. Results: Icariin significantly suppressed the proliferation of SKOV-3 cells. Furthermore, icariin stalled cell cycle and induced apoptosis by blocking TNKS2/Wnt/ß-catenin pathway through upregulating the level of miR-1-3p. Finally, icariin dramatically suppressed tumor growth in vivo. Conclusions: In this study, we demonstrated for the first time that icariin significantly attenuated the growth of ovarian tumor in xenograft mouse model. Furthermore, we systematically revealed that icariin attenuates the tumor progression by suppressing TNKS2/Wnt/ß-catenin signaling via upregulating the level of miR-1-3p in ovarian cancer with transcriptome analysis.

Enhanced Response for Foodborne Pathogens Detection by Au Nanoparticles Decorated ZnO Nanosheets Gas Sensor.

Listeria monocytogenes is a hazardous foodborne pathogen that is able to cause acute meningitis, encephalitis, and sepsis to humans. The efficient detection of 3-hydroxy-2-butanone, which has been verified as a biomarker for the exhalation of Listeria monocytogenes, can feasibly evaluate whether the bacteria are contained in food. Herein, we developed an outstanding 3-hydroxy-2-butanone gas sensor based on the microelectromechanical systems using Au/ZnO NS as a sensing material. In this work, ZnO nanosheets were synthesized by a hydrothermal reaction, and Au nanoparticles (~5.5 nm) were prepared via an oleylamine reduction method. Then, an ultrasonic treatment was carried out to modified Au nanoparticles onto ZnO nanosheets. The XRD, BET, TEM, and XPS were used to characterize their morphology, microstructure, catalytic structure, specific surface area, and chemical composition. The response of the 1.0% Au/ZnO NS sensors vs. 25 ppm 3-hydroxy-2-butanone was up to 174.04 at 230 °C. Moreover, these sensors presented fast response/recovery time (6 s/7 s), great selectivity, and an outstanding limit of detection (lower than 0.5 ppm). This work is full of promise for developing a nondestructive, rapid and practical sensor, which would improve Listeria monocytogenes evaluation in foods.

Determination of arsenic in Chinese mitten crabs (Eriocheir sinensis): Effects of cooking and gastrointestinal digestion on food safety.

This study used the sexually mature Chinese mitten crabs as the research object, and the total arsenic and six major species were determined by high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The influence of three common cooking methods on the forms of arsenic and content in different edible parts of crabs were explored. Furthermore, the bioavailability of arsenic and its different forms in the crabs were studied by in vitro gastrointestinal digestion. Based on the risk assessment of arsenic in gastrointestinal digestion, the results showed that the Target Hazard Quotient (THQ) of arsenic was less than 1, which did not pose a significant health risk, but the risk of carcinogenesis of arsenic can not be ignored. Considering the effects of cooking and gastrointestinal digestion into account, a more realistic estimate of the risk associated with the consumption of Chinese mitten crabs can be deciphered.

Composition engineering of AZO films for controlled photon-electron conversion and ultrafast nonlinear optical behavior.

Exploring micro-nano photonic crystals as nonlinear optical switching and optical limiting devices for Gaussian light fields with ultrashort pulse widths has attracted extensive research, mainly originating from its controllable modulation of the third/fifth-order nonlinear optical behavior and ultrafast carrier dynamics. In this work, Al-doped ZnO (AZO) films with controllable and excellent third-order nonlinear optical behavior have been uniformly deposited on quartz substrates by a single-step co-sputtering method. Al dopant-dependent ultrafast carrier dynamics and nonlinear optical properties in hexagonal ZnO films are discussed. The bonding mode of Al atoms in the ZnO lattice changed from substitutional to substitutional-decoration, which has been controllably achieved at different DC sputtering powers. The strain, crystallinity, grain size, dislocation density, and texture coefficient of the sample were quantitatively calculated by XRD and Raman spectroscopy, which confirmed that the phase parameters can be regulated by the sputtering power. In addition, Hall test and photoluminescence spectra showed the contribution of the donor level on the band structure and the electron transfer characteristics, which will provide a strategy for understanding multi-type carrier dynamics under strong light fields. The finite-difference time-domain method was used to simulate the linear optical absorption/transmittance of the sample under a plane-wave optical field, which proved that the light-matter interaction failed to be significantly suppressed by shading and scattering effects. The carrier relaxation process and nonlinear absorption/refractive effects were controllably optimized by dopant Al atoms, which were confirmed by Z-scan and transient absorption spectroscopy. Compared with pure ZnO films, the third-order nonlinear refraction and absorption coefficients of AZO-power films can reach -8.926 × 10-15 m2 W-1 and -0.634 × 10-7 m W-1, respectively. AZO films with ultrafast carrier dynamics and controllable excellent third-order nonlinear optical coefficients can be used as all-optical switches and optical limiting devices, which provide a reference for advanced micro-nano optical materials.

Ultra-efficient trimethylamine gas sensor based on Au nanoparticles sensitized WO3 nanosheets for rapid assessment of seafood freshness.

Trimethylamine (TMA) is an organic amine gas used as an important index to assess the seafood freshness. In this work, an ultra-efficient trimethylamine gas sensor was constructed by ultrasonic treatment loading of Au nanoparticles (∼4 nm) on WO3 nanosheets prepared by solvothermal self-assembly method. The response of the sensor to 25 ppm TMA was as high as 217.72 (Rair/Rgas) at 300 ℃. In addition, the Au/WO3 nanosheets sensor exhibited rapid response-recovery time (8 s/6 s), low detection limit (0.5 ppm), and high selective detection of TMA. Moreover, the composition of volatiles produced by decay of Larimichthys crocea (0-15 days) was examined, which proved that the detection of TMA by the Au/WO3 sensor can evaluate the freshness of Larimichthys crocea. Such a magnificent gas sensing performance reveals that the Au/WO3 sensor has remarkable application potential in rapid and non-destructive seafood freshness assessment on the spot.

Gelatin/Chitosan Films Incorporated with Curcumin Based on Photodynamic Inactivation Technology for Antibacterial Food Packaging.

Photodynamic inactivation (PDI) is a new type of non-thermal sterilization technology that combines visible light with photosensitizers to generate a bioactive effect against foodborne pathogenic bacteria. In the present investigation, gelatin (GEL)/chitosan (CS)-based functional films with PDI potency were prepared by incorporating curcumin (Cur) as a photosensitizer. The properties of GEL/CS/Cur (0.025, 0.05, 0.1, 0.2 mmol/L) films were investigated by evaluating the surface morphology, chemical structure, light transmittance, and mechanical properties, as well as the photochemical and thermal stability. The results showed a strong interaction and good compatibility between the molecules present in the GEL/CS/Cur films. The addition of Cur improved different film characteristics, including thickness, mechanical properties, and solubility. More importantly, when Cur was present at a concentration of 0.1 mM, the curcumin-mediated PDI inactivated >4.5 Log CFU/mL (>99.99%) of Listeria monocytogenes, Escherichia coli, and Shewanella putrefaciens after 70 min (15.96 J/cm2) of irradiation with blue LED (455 ± 5) nm. Moreover, Listeria monocytogenes and Shewanella putrefaciens were completely inactivated after 70 min of light exposure when the Cur concentration was 0.2 mM. In contrast, the highest inactivation effect was observed in Vibrio parahaemolyticus. This study showed that the inclusion of Cur in the biopolymer-based film transport system in combination with photodynamic activation represents a promising option for the preparation of food packaging films.

Proapoptotic Effect of Icariin on Human Ovarian Cancer Cells via the NF-[Formula: see text]B/PI3K-AKT Signaling Pathway: A Network Pharmacology-Directed Experimental Investigation.

Based on network pharmacology tools and public bioinformatics databases, the pharmacodynamic target and key mechanism of icariin (ICA) in the treatment of ovarian cancer (OC) were identified and experimentally verified. Our previous research showed that TNF, MMP9, STAT3, PIK3CA, ERBB2, MTOR, IL2, PTGS2, KDR and F2 are important targets of ICA in the treatment of OC. TNF, as a hub gene in tumor tissues, was associated with poor prognosis. ICA acted on OC mainly through the biological functions of various kinases, and the pathway with the highest accuracy ([Formula: see text]-value) was PI3K. Meanwhile, we observed a close upstream and downstream relationship between NF-[Formula: see text]B and the Pl3K-AKT pathway. This study further verified the mechanism of ICA in promoting apoptosis of SKOV3 cells through the NF-[Formula: see text]B signaling pathway and the tandem relationship between NF-[Formula: see text]B and the Pl3K-AKT pathway. The assay results demonstrated that ICA can promote the apoptosis of SKOV3 cells as indicated by the proapoptotic markers Bax, Bcl-xl and Caspase-3 and the key factors of the NF-[Formula: see text]B signaling pathway (NF-[Formula: see text]Bp65, p-NF-[Formula: see text]Bp65, p-I[Formula: see text]B[Formula: see text] and I[Formula: see text]B[Formula: see text]. ICA can block the classical NF-[Formula: see text]B pathway by inhibiting I[Formula: see text]B[Formula: see text] phosphorylation and consequently blocking the activation of the NF-[Formula: see text]B pathway in SKOV3 cells. ICA can also promote apoptosis by blocking the activation of the NF-[Formula: see text]B pathway in SKOV3 cells via inhibition of NF-[Formula: see text]Bp65 nuclear translocation. After using a PI3K pathway inhibitor, we further discovered that ICA may reduce AKT signal transduction by inhibiting the level of Akt phosphorylation, resulting in a loss of PI3K/Akt-dependent activation of the NF-[Formula: see text]B pathway.

Anti-tyrosinase, antioxidant and antibacterial activities of gallic acid-benzylidenehydrazine hybrids and their application in preservation of fresh-cut apples and shrimps.

A series of gallic acid-benzylidenehydrazine hybrids were synthesized and evaluated for their tyrosinase inhibitory activity. Thereinto, compounds 5d and 5f potently inhibited tyrosinase with IC50 of 15.3 and 3.3 µM, compared to kojic acid (44.4 µM). The inhibition mechanism suggested that 5d and 5f not only chelated with Cu2+, but also reduced Cu2+ to Cu1+ in the tyrosinase active site. Additionally, 5d and 5f exhibited strong DPPH scavenging and antibacterial activities against Vibrio parahaemolyticu and Staphylococcus aureus, which can be attributed to the function of gallic acid and hydrazone moiety. These compounds also exhibited capacity to preserve fresh-cut apples and shrimps. Finally, 5d and 5f exhibited low cytotoxic activity in a human cell line (HEK293). Therefore, these compounds possess anti-tyrosinase, antioxidant, and antibacterial activities, and can be used in the development of novel food preservatives.

A systematic review of synthetic tyrosinase inhibitors and their structure-activity relationship.

Tyrosinase is a copper-containing oxidation enzyme, which is responsible for the production of melanin. This enzyme is widely distributed in microorganisms, animals and plants, and plays an essential role in undesirable browning of fruits and vegetables, antibiotic resistance, skin pigment formation, sclerotization of cuticle, neurodegeneration, etc. Hence, it has been recognized as a therapeutic target for the development of antibrowning agents, antibacterial agents, skin-whitening agents, insecticides, and other therapeutic agents. With great potential application in food, agricultural, cosmetic and pharmaceutical industries, a large number of synthetic tyrosinase inhibitors have been widely reported in recent years. In this review, we systematically summarized the advances of synthetic tyrosinase inhibitors in the literatures, including their inhibitory activity, cytotoxicity, structure-activity relationship (SAR), inhibition kinetics, and interaction mechanisms with the enzyme. The collected information is expected to provide a rational guidance and effective strategy to develop novel, potent and safe tyrosinase inhibitors for better practical applications in the future.