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Methods capable of distributing antitumour therapeutics uniformly throughout an entire tumour and that can suppress metastasis at the same time, would be of great significance in improving cancer treatment. Bacteria-mediated synergistic therapies have been explored for better specificity, temporal and spatial controllability, as well for providing regulation of the immune microenvironment, in order to provide improved cancer treatment. To achieve this goal, here we developed an engineered bacteria delivery system (GDOX@HSEc) using synthetic biology and interfacial chemistry technologies. The engineered bacteria were concurrently modified to express heparin sulfatase 1 (HSulf-1) inside (HSEc), to attach doxorubicin-loaded glycogen nanoparticles (GDOX NPs) on their surface. Here we demonstrate that HSEc can actively target and colonise tumour sites resulting in HSulf-1 overexpression, thereby suppressing angiogenesis and metastasis. Simultaneously, the GDOX NPs were able to penetrate into tumour cells, leading to intracellular DNA damage. Our results confirmed that a combination of biotherapy and chemotherapy using GDOX@HSEc resulted in significant melanoma suppression in murine models, with reduced side effects. This study provides a powerful platform for the simultaneous delivery of biomacromolecules and chemotherapeutic drugs to tumours, representing an innovative strategy potentially more effective in treating solid tumours. STATEMENT OF SIGNIFICANCE: An original engineered bacteria-based system (GDOX@HSEc) was developed using synthetic biology and interfacial chemistry technologies to concurrently produce naturally occurring heparin sulfatase 1 (HSulf-1) inside and anchor doxorubicin-loaded glycogen nanoparticles on the surface. GDOX@HSEc allowed for combined local delivery of chemotherapeutic agents along with the enzymes and immunostimulatory bacterial adjuvants, which resulted in a synergistic action in the inhibition of tumour growth and metastasis. The study provides a potential therapeutic approach that allows therapeutic agents to be distributed in a spatiotemporally controllable manner in tumours for combinatorial enhanced therapy.

International audience; In Arabidopsis, the receptor-like kinase (RLK) FERONIA (FER) senses peptide ligands in the plasma membrane (PM), modulates plant growth and development, and integrates biotic and abiotic stress signaling for downstream adaptive responses. However, the molecular interplay of these diverse processes is largely unknown.Here, we show that FER, the receptor of Rapid Alkalinization Factor 1 (RALF1), physically interacts with C2 domain ABA-related (CAR) proteins to control the nano-organization of the PM. During this process, the RALF1-FER pathway upregulates CAR protein translation, and then more CAR proteins are recruited to the PM. This acts as a rapid feedforward loop that stabilizes the PM liquid-ordered phase. FER interacts with and phosphorylates CARs, thereby reducing their lipid-binding ability and breaking the feedback regulation at later time points.The formation of the flg22-induced FLS2-BAK1 immune complex, which depends on the integrity of FER-containing nanodomains, is impaired in fer and pentuple car14569 mutant.Together, we propose that the FER-CAR module controls the formation of PM nano-organization during RALF signaling through a self-contained amplifying loop including both positive and negative feedback.

With the advent of the era of big data, the application of big data analytics in entrepreneurial activities has become increasingly prevalent. However, research on the relationship between big data analytic capabilities and entrepreneurial activities is still in its infancy, and the mechanism by which the two interact remains unclear. Drawing on resource-based theory and entrepreneurial process theory, this research examines the impact mechanism of big data analytic capabilities on the growth performance of start-up enterprises and explores the mediating role of entrepreneurial opportunity recognition and entrepreneurial opportunity exploitation. Empirical analysis reveals that big data analytic capabilities have a significant positive impact on the growth performance of start-up enterprises; entrepreneurial opportunity exploitation plays a mediating role in the relationship between big data analytic capabilities and the growth performance of start-up enterprises, but entrepreneurial opportunity recognition does not show a significant mediating effect between the two; and entrepreneurial opportunity recognition and entrepreneurial opportunity exploitation play a chain-mediated role in the relationship between big data analytic capabilities and the growth performance of start-up enterprises. These research findings enrich the study of digital entrepreneurship and provide valuable references for the entrepreneurial practice of start-up enterprises.

Chemotherapy is currently one of the most widely used treatments for cancer. However, traditional chemotherapy drugs normally have poor tumor selectivity, leading to insufficient accumulation at the tumor site and high systemic cytotoxicity. To address this issue, we designed and prepared a boronic acid/ester-based pH-responsive nano-drug delivery system that targets the acidic microenvironment of tumors. We synthesized hydrophobic polyesters with multiple pendent phenylboronic acid groups (PBA-PAL) and hydrophilic PEGs terminated with dopamine (mPEG-DA). These two types of polymers formed amphiphilic structures through phenylboronic ester linkages, which self-assembled to form stable PTX-loaded nanoparticles (PTX/PBA NPs) using the nanoprecipitation method. The resulting PTX/PBA NPs demonstrated excellent drug encapsulation efficiency and pH-triggered drug-release capacity. In vitro and in vivo evaluations of the anticancer activity of PTX/PBA NPs showed that they improved the pharmacokinetics of drugs and exhibited high anticancer activity while with low systemic toxicity. This novel phenylboronic acid/ester-based pH-responsive nano-drug delivery system can enhance the therapeutic effect of anticancer drugs and may have high potential for clinical transformations.

We address the existence, stability, and propagation dynamics of both one- and two-dimensional defect solitons supported by optical lattice with saturable nonlinearity in fractional Schrödinger equation. Under the influence of fractional effect, in one dimension, solitons exist stably in limited regions in the semi-infinite bandgap with high and low power both for a negative and positive defect lattice. In the first bandgap, solitons are stable for negative defect lattice, while unstable for positive defect lattice. In the second bandgap, only stable solitons can propagate in small regions for the positive defect lattice. With increasing the Lévy index from 1 to 2, the power of the defect solitons decreases in the semi-infinite bandgap and increases in the first bandgap. Linear stability analyses show that, the domains of stability for defect solitons strongly depend on the Lévy index, defect strength and different bandgaps. In two dimension, defect solitons can exist stably at high and moderate power regions in the semi-infinite bandgap and all regions in the first bandgap with negative defect lattice, while they are stable at high, moderate and low power regions in the semi-infinite bandgap and unstable in the first bandgap with positive defect lattice.

Accurate acquisition of image contrast is an important factor for measuring modulation transfer function and minimum resolvable contrast of camera. Under low illumination, image from intensified charge-coupled device exhibits ion feedback noise with high brightness, resulting in lower signal-to-noise ratio of the image. Thus, one cannot obtain easily the accurate image contrast results by using the conventional contrast calculation method. In this paper, the ion feedback noise of the rectangular target image under low illumination is first reduced by means of constrained noise screening method and asymmetrical orientation window weighted mean filling algorithm. According to the spatial height correlation of the rectangular target image, the maximum sampling region is then founded by using spatial one-way statistical average algorithm combined with Otsu binarization. The image contrast is finally calculated after removing the fuzzy interval in the boundary between black and white stripes. It is shown that the method proposed can achieve the maximum sampling region acquisition and the contrast calculation for the image captured under low illumination, which reduces the error of calculation contrast caused by manually selecting the sampling region.

To reduce the adverse physical effects on the oral mucosa caused by excessive hardness of betel nut fibres, steam explosion was used to soften betel nuts. The effect of 3 operating parameters (pressure holding time, explosion pressure and initial moisture content) on the morphology, texture and chemical composition of the betel nuts was investigated. The fibre hardness and Shore hardness decreased by 56.17%-89.28% and 7.03%-34.29%, respectively, and the transverse tensile strength and fibre tensile strength also decreased by up to 60.72% and 24.62%, respectively. Moreover, the coefficient of friction and moisture content increased. After steam explosion, the betel nut increased in transverse diameter, became darker and more yellow‒red in colour, and showed a damaged microstructure. The contents of lignin, hemicellulose, free phenol, bound phenol and alkaloids decreased after steam treatment, with total phenols and alkaloids decreasing from 44.07 mg(GAE)/g and 7.84 mg/g to 30.61 mg(GAE)/g and 6.50 mg/g, respectively, after the A-50 s treatment condition. A slight increase in cellulose was observed when steam explosion conditions exceeded 80 s or 0.75 MPa. The steam explosion increased the quantity of phenols, alkaloids and soluble solids released from the betel nut under the same simulated release conditions. The research also showed that the explosion efficiency was positively correlated with the pressure holding time and explosion pressure, while the initial moisture content was reduced the explosion efficiency. Therefore, steam explosion is an effective pretreatment approach to soften betel nut and facilitate healthy development of the betel nut industry.

AimsThis study aimed to investigate the mechanism of linalool against Pseudomonas lundensis and its application on beef.Methods and ResultsField emission scanning electron microscopy found that linalool exerted antibacterial activity with a minimum inhibitory concentration (MIC) of 1.5 ml l−1 by disrupting cell structure. Loss of cell membrane integrity was monitored due to leakage of nucleic acids and K+. In addition, respiratory depression appeared in Ps. lundensis based on inhibition of enzyme activities including hexokinase (HK), glucose 6-phosphate dehydrogenase (G6PDH), phosphofructokinase (PFK), pyruvate kinase (PK), pyruvate dehydrogenase (PDH), citrate synthase (CS), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH). Subsequently, energy limitation also occurred according to the decrease in ATP content and ATPase activity. Molecular docking confirmed that linalool can combine with enzymes in cell wall (ddlB) and energy synthesis (AtpD) pathways to exert antibacterial effect. Of note, linalool has advantages for beef preservation by delaying quality changes including pH, total volatile basic nitrogen (TVB-N) and total viable count (TVC).ConclusionsLinalool has significant inhibitory effect on Ps. lundensis, and respiratory depression driven by membrane damage is the main inhibitory mechanism.

Multidrug resistance (MDR) is the main challenge faced by cancer chemotherapy. Drug-conjugate offers a promising strategy for breast cancer therapy. In this regard, we developed a DNVM multifunctional drug delivery system by crosslinking doxorubicin (DOX) and vitamin E succinate (VES) with a pH-sensitive hydrazone bond and then encapsulated the DOX-NN-VES prodrug into pH-sensitive hyaluronic acid-2-(octadecyloxy)-1,3-dioxan-5-amine (HOD) micelles. DOX resistant MCF-7/ADR cell were adopted as a model to study the capability and mechanism of MDR reversal. DNVM exhibited much higher cytotoxicity and cell uptake efficiency compared with that of acid-insensitive DOX-VES loaded HOD micelles (DVSM) and DOX loaded HOD micelles (DOXM), indicating the better capacity of DNVM for the reversal of MDR. Moreover, DNVM prevented drug efflux more effectively, inhibited the expression of P-gp, induced excessive production of reactive oxygen species and affected the expression of apoptosis-related proteins. In vivo experiments showed that DNVM significantly inhibited the tumor growth with no obvious changes in the body weight of MCF-7/ADR cells-bearing nude mice. The results suggested that the "double gain" DNVM can synergistically enhance the efficacy of chemotherapeutics for DOX resistant tumor cells and has the potential to overcome tumor MDR. STATEMENT OF SIGNIFICANCE: A dual-functional pH-sensitive doxorubicin - vitamin E succinate prodrug was developed and loaded into tumor microenvironment-sensitive hyaluronic acid-2-(octadecyloxy)-1,3-dioxan-5-amine micelle system (DNVM) for sequencing stimuli-release and overcoming doxorubicin resistance. The "double gain" DNVM can synergistically enhance the efficacy of chemotherapeutics for doxorubicin resistant tumor cells and has the potential to overcome tumor multiple drug resistance.

In this study, we conducted a 56-d feeding trial to investigate the effects of replacing the fish oil (FO) with palm oil (PO) on the performance, tissue fatty acid (FA) composition, and mRNA levels of genes related to hepatic lipid metabolism in grouper (Epinephelus coioides). Five isolipidic (13% crude lipid) and isonitrogenous (48% CP) diets were formulated by incrementally adding PO to the control diet (25% fish meal and 9% added FO) to replace FO in the control diets. Triplicate groups of 30 groupers (initial weight: 12.6 ± 0.1 g) were fed one of the diets twice daily, to apparent satiety. The replacement of FO with 50% PO revealed maximum growth without affecting the performance and whole-body proximate compositions, and replacing FO with 100% PO revealed a comparable (P > 0.05) growth with that of the control diet, suggesting PO as a suitable alternative to FO. The analysis of FA profiles in the dorsal muscle and liver though reflected the FA profile of the diet, PO substitutions above 50% could compromise (P

Copper-cysteamine as a new generation of sensitizers can be activated by light, X-rays, microwaves, or ultrasound to produce reactive oxygen species. X-ray induced photodynamic therapy (X-PDT) has been studied extensively; however, most of the studies reported so far were conducted in the laboratory, which is not conducive to the clinical translation conditions. In this contribution, for the first time, we investigated the treatment efficiency of copper-cysteamine (Cu-Cy) based X-PDT by mimicking the clinical conditions with a clinical linear accelerator and building deep-seated tumor models to study not only the effectiveness but also its effects on the cell migration and proliferation in the level of the cell, tissue, and animal. The results showed that, without X-ray irradiation, Cu-Cy nanoparticles (NPs) had a low toxicity in HepG2, SK-HEP-1, Li-7, and 4T1 cells at a concentration below 100 mg/L. Interestingly, for the first time, it was observed that Cu-Cy mediated X-PDT can inhibit the proliferation and migration of these cell lines in a dose-dependent manner. Antigen markers of migration and cell proliferation, proliferating cell nuclear antigen (PCNA) and E-cadherin, from tumor tissue in the X-PDT group were remarkably different from that of the control group. Furthermore, the MRI assessment showed that the Cu-Cy based X-PDT inhibited the growth of deeply located tumors in mice and rabbits (p, Graphical abstract Image 1, Highlights • X-PDT was studied by mimicking the clinical conditions with a clinical linear accelerator and building deep-seated tumor. • Cu-Cy mediated X-PDT can inhibit the proliferation and migration of these cell lines in a dose-dependent manner. • Cu-Cy based X-PDT inhibited the growth of deeply located tumors in mice and rabbits without any obvious toxicities in vivo. • Cu-Cy NPs have a safe and promising clinical application prospect in X-PDT to improve the efficiency of radiotherapy.

The study aimed to investigate the effects of dietary sodium butyrate (NaBT) supplementation on the gut health of largemouth bass (Micropterus salmoides) fed with a high soybean meal diet. Three isonitrogenous and isolipidic diets were formulated: a high fishmeal group (Control); a high soybean meal group (SBM), in which the 30% fishmeal protein in the Control diet was replaced by soy protein; and an NaBT group, in which 0.2% NaBT was added to the SBM diet. Each diet was fed to triplicate tanks (20 fish in each tank). After 8 weeks of feeding trial, the distal intestine and intestinal digesta of the fish in each treatment were sampled. The results showed that fishmeal replacement and NaBT supplementation did not affect fish growth performance. Dietary 0.2% NaBT supplementation improved intestinal morphology, increasing the villus width and villus height and reducing the width of lamina propria. The distal intestine of fish in the control and NaBT groups demonstrated lower activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GPx) and a lower malondialdehyde (MDA) content, compared with the fish in the SBM group. Moreover, the addition of 0.2% NaBT in the feed significantly decreased the expression of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) compared to the SBM diet. PCoA and UPGMA analyses based on weighted UniFrac distances demonstrated that intestinal microbial communities in the NaBT group were closer to those in the control group than to those in the SBM group. In addition, dietary 0.2% NaBT supplementation significantly increased the abundance of Firmicutes and Bacteroidetes and decreased the abundance of Tenericutes at the phylum level. Furthermore, the abundance of Bacteroides, Lachnospiraceae_unclassified, and Lachnospiraceae_uncultured was significantly increased, while that of Mycoplasma was significantly decreased in fish intestine at NaBT group at the genus level. In conclusion, dietary NaBT supplementation had beneficial roles in protecting the gut health of largemouth bass from the impairments caused by soybean meal.

The aim of the study is to investigate whether dietary Chlorella sorokiniana supplementation could improve growth performance, antioxidant status, and immune response of Oncorhynchus mykiss. Three isonitrogenous (47%) and isolipidic (16.5%) diets supplemented with 0% (Control), 5% (5% CS), and 10% C. sorokiniana meal (10% CS) were assigned to O. mykiss (three replicates per diet, 30 fish in each replicate, initial body weight 165.24 ± 0.46 g). The results indicated that O. mykiss fed with 5% CS diet had an increased feeding rate (FR), specific growth rate (SGR), and weight gain rate (WGR) compared to the control (P

The aim of the present study was to investigate the effect of glycosylation with sugar beet pectin (SBP) on the interfacial behaviour and emulsifying ability of coconut protein (CP). The physical stabilities of the emulsions were predicted by transmission variation, droplet distribution and zeta potentials. The results showed that SBP-CP-stabilized emulsions showed better stability during centrifugation than those stabilized by CP because SBP-CP reduced the degree of variation in the CP transmission profile. The adsorption kinetics of all emulsifiers at the oil-water interface were determined to investigate the relationship between the interfacial behaviour and emulsion stability. The presence of SBP considerably reduced the adsorption rate of CP (0.698 mN/m/s1/2) and hampered the development of a highly viscoelastic network at the oil-water interface. The values of the dilatational elastic modulus (Ed = 19.477 mN/m) and dilatational viscous modulus (E = 19.719 mN/m) were approximately equal, indicating that the adsorption process was mainly dominated by elastic behaviour. Additionally, the SBP-CP interaction enhanced the dilatational property of the CP-absorbed layer.