Angiotensin II type-2 receptor signaling facilitates liver injury repair and regeneration via inactivation of Hippo pathway.

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.

Angiotensin II type-2 receptor attenuates liver fibrosis progression by suppressing IRE1α-XBP1 pathway.

The renin-angiotensin system (RAS) has been recognized as a crucial contributor to the development of liver fibrosis, and AT2R, an essential component of RAS, is involved in the progression of liver fibrosis. However, the underlying mechanisms by which AT2R modulates liver fibrosis remain elusive. Here, we report that AT2R was induced to be highly expressed during the progression of liver fibrosis, and the elevated AT2R attenuates liver fibrosis by suppressing IRE1α-XBP1 pathway. In this study, we found that AT2R is not expressed in the no cirrhotic adult liver, but is induced expression during liver fibrosis in both cirrhotic patients and fibrotic mice models. Upregulated AT2R inhibits the activation and proliferation of hepatic stellate cells (HSCs). In addition, our study showed that during liver fibrosis, AT2R deletion increased the dimerization activation of IRE1α and promoted XBP1 splicing, and the spliced XBP1s could promote their transcription by binding to the AT2R promoter and repress the IRE1α-XBP1 axis, forming an AT2R-IRE1α-XBP1 negative feedback loop. Importantly, the combination treatment of an AT2R agonist and an endoplasmic reticulum stress (ER stress) alleviator significantly attenuated liver fibrosis in a mouse model of liver fibrosis. Therefore, we conclude that the AT2R-IRE1α signaling pathway can regulate the progression of liver fibrosis, and AT2R is a new potential therapeutic target for treating liver fibrosis.

Preparation and performance testing of corn starch/pullulan/gallic acid multicomponent composite films for active food packaging.

The present study investigated the mechanical characteristics, hydrophobicity, antioxidant and antibacterial properties, FTIR, SEM and XRD of films fabricated with corn starch and pullulan (CS/PUL) by adding different concentrations of Gallic acid (GA) (0%, 0.5%, 1.0%, 1.5% w/v). The mechanical strength and opacity of CS/PUL films were enhanced by the addition of 1.0% GA. The water vapor permeability (WVP) of CS/PUL films was significantly lower in films with GA compared to those without (P < 0.05). The addition of GA, especially at concentrations of 1.0% and 1.5%, resulted in considerably better free radical scavenging activities on DPPH than films without GA (P < 0.05). Interestingly, the highest water contact angle (WCA) value was observed in films with 0.5% GA, indicating stronger hydrophobicity. Furthermore, the antibacterial capabilities of the films, particularly against E. coli and P. aeruginosa, improved with an increase in GA concentration. The results of FTIR, SEM and XRD analyses showed that GA was well distributed in the CS/PUL matrix.

Insight into the mechanism of water-insoluble dietary fiber from star anise (Illicium verum Hook. f.) on water-holding capacity of myofibrillar protein gels.

This study aimed to determine the efficacy of star anise dietary fiber (SADF) in alleviating the oxidative damage of myofibrillar protein (MP) from the perspective of volatile components. SADF and SADF without essential oils (EOs) (NSADF) were added to oxidized MP. The addition of NSADF and SADF improved the water-holding capacity (WHC) and gel strength, with the 0.4% addition showing the highest values. Moreover, the WHC of MP from the SADF-treated group was significantly higher than that from the NSADF-treated group at the same dosage, suggesting that EOs in SADF improved the WHC through antioxidation. EOs in SADF prevented the attack of hydroxyl radicals on MP, increasing the ß-sheet level and decreasing the random coil level, which was supported by the results of FT-IR, carbonyl content, and sulfhydryl content. Limonene and anisaldehyde present in EOs played an antioxidant role, and anisaldehyde could scavenge free radicals through demethoxylation.

Effects of Non-Enzymatic Browning and Lipid Oxidation on Color of Ready-to-Eat Abalone during Accelerated Storage and Its Control.

The deepening of color of ready-to-eat (RTE) abalone during storage leads to sensory quality degradation, which seriously affects the shelf life of products and consumers' purchasing desire. The goal of this study is to look into the causes of non-enzymatic browning and lipid oxidation, as well as how to control them, and their effect on the color of RTE abalone during storage. The control, bloodletting and antioxidants groups (lactic acid, citric acid and 4-hexylresorcinol) of RTE abalone were stored for 0, 20 and 40 days at 40 °C, respectively, to explore the rule and mechanism of the color change in RTE abalone. This research shows that RTE abalone undergoes browning during storage. Meanwhile, the content of reducing sugar, phenols and unsaturated fatty acids decreases, while the formation of lipid hydroperoxides and aldehydes increases during storage. In addition, the color change in RTE abalone during storage is mainly related to the Maillard reaction, while the lipid oxidation mainly forms pyrrole and participates in the Strecker degradation process as part of the Maillard reaction. The quality of RTE abalone can be maintained by controlling browning effectively as well as lipid oxidation through bloodletting and the addition of antioxidants to ensure that RTE abalone has high storage stability. According to our research, bloodletting and the addition of antioxidants to RTE abalone have a good application prospect and popularizing value in the storage of RTE abalone.

Enhanced crystallization, heat resistance and transparency of poly(lactic acid) with self-assembling bis-amide nucleator.

The application of poly(lactic acid) (PLA) is limited by its low crystallization rate. Conventional methods to increase crystallization rate usually result in a significant loss of transparency. In this work, a bundled bis-amide organic compound N'-(3-(hydrazinyloxy)benzoyl)-1-naphthohydrazide (HBNA) was used as a nucleator to prepare PLA/HBNA blends with enhanced crystallization, heat resistance and transparency. HBNA dissolves in PLA matrix at high temperature and self-assembles into bundle microcrystals by intermolecular hydrogen bonding at a lower temperature, which induces PLA to form ample spherulites and "shish-kebab-like" structure rapidly. The effects of HBNA assembling behavior and nucleation activity on the PLA properties and the corresponding mechanism are systematically investigated. As a result, the crystallization temperature of PLA increased from 90 °C to 123 °C by adding as low as 0.75 wt% of HBNA, and the half-crystallization time (t1/2) at 135 °C decreased from 31.0 min to 1.5 min. More importantly, the PLA/HBNA maintains good transparency (transmittance > 75 % and haze is ca. 27 %) due to the decreased crystal size, even though the crystallinity of PLA is increased to 40 %, which also led to good heat resistance. The present work is expected to expand the application of PLA in packaging and other fields.

Analysis of texture properties and water-soluble fraction proteome of sea cucumber body wall with different boiling heating treatment.

Label-free quantitative proteomic analysis was utilized to determine the key proteins that affect texture properties of sea cucumber body wall (SCBW) with different boiling heating treatment. 862, 363, 315, and 258 proteins were confirmed in water-soluble fractions from fresh group, 0.5 h-, 2 h- and 4 h-heat treatment group, respectively. During boiling heating treatment, proteins with an increased abundance in water-soluble fraction primarily belong to structural proteins, such as collagens, microfibril-associated proteins, glycoproteins, and muscle proteins. It was speculated that the degradation of these structural proteins caused the progressive disintegration of network skeleton of collagen fibres and FMs as well as the gelatinization, thus resulted in the decrease of hardness and shear force. Besides, the degradation of FMs was occurred layer by layer during boiling heating treatment, and the fibrilin-1 outer layer degraded first, followed by the fibrilin-2 core component.

Differences in texture and digestive properties of different parts in boiled abalone muscles.

Differences in texture and digestive properties of different parts in 80 °C-boiled abalone muscle (adductor and transition part) after different processing time were investigated. With the extension of boiling time, the shear force and hardness of adductor increased first (6 min) and then decreased (30 min and 240 min), while the two indexes of transition part dramatically decreased after boiling for 6 min and then maintained until 240 min. Meanwhile, for adductor, the degree of protein hydrolysis, protein digestibility, and peptide transport levels declined with the extension of boiling time; While for transition part, those protein digestion and transport indexes significantly decreased first (6 min and 30 min) and then increased (240 min). By contrast, the adductor contained higher myofibrillar proteins content but lower collagen content than the transition part, which contributed to the differences in texture and digestive properties of the boiled samples.

Effect of boiling on texture of abalone muscles and its mechanism based on proteomic techniques.

The precise mechanism of texture changes in abalone muscles during boiling was investigated using quantitative proteomic analysis. A total 353 water-soluble proteins were identified in fresh abalone muscle. The number was decreased to 233 (6 min) and 201 (30 min), and then increased to 271 (240 min) during boiling. The undetectable protein in water-soluble fraction caused by boiling mainly belong to hemocyanins, protein kinases, dehydrogenases, phosphorylases, and transferases, while the newly identified proteins in water-soluble fraction during boiling mainly belong to collagen and myofibrillar proteins (MPs).Additionally, results also showed that boiling caused protein oxidation, denaturation, aggregation, crosslinking and degradation. Combined with the texture changes of abalone muscles during boiling, it was speculated that the oxidation, denaturation, aggregation and crosslinking of proteins led to the increase of shear force, however, the degradation of structural proteins such as MPs and collagen caused the decreases in shear force and hardness.

Effects of antioxidants of bamboo leaves on protein digestion and transport of cooked abalone muscles.

The effects of oxidation on protein digestion and transport in cooked abalone muscles were investigated using a combination of simulated digestion and everted-rat-gut-sac models for the first time. Boiling heat treatments caused protein oxidation in the abalone muscles, reflected by increases in the carbonyl group and disulfide bond contents, protein hydrophobicity and aggregation degree, as well as decreases in the free sulfhydryl group and amino acid contents. Protein oxidation significantly inhibited the degree of hydrolysis, digestion rate, and digestibility of the abalone muscles in the simulated digestion model. The results from the everted-rat-gut-sac model showed that amino acid and peptide transport levels from the digestion products of the cooked abalone muscles were lower than those of the uncooked samples. In contrast, the addition of antioxidants of bamboo leaves mitigated heat-treatment-induced protein oxidation, aggregation and increased hydrophobicity, and consequently improved abalone muscle protein digestibility and transport levels.

Enhanced crystallization and storage stability of mechanical properties of biosynthesized poly (3-hydroxybutyrate-co-3-hydroxyhexanate) induced by self-nucleation.

The poor mechanical properties induced by unsatisfactory crystallization ability limit the widespread use of biosynthesized poly (3-hydroxybutyrate-co-3-hydroxyhexanate) (PHBH). In this work, poly (3-hydroxybutyrate) (PHB) with a high melting point was first used as a homogeneous nucleating agent to increase the crystallization rate of PHBH by a self-nucleation method with a wider processing temperature window and crystallization kinetics and storage stability of mechanical properties of the PHBH/PHB mixtures were systematically investigated. By controlling the processing temperature and PHB content, the crystal nucleus density and crystallization rate of PHBH could be greatly increased while secondary crystallization was inhibited. When the processing temperature is 185 °C and PHB content is 20 wt%, the half crystallization time is shortened by 96% and the crystallinity was increased to 37.2%. Meanwhile, the mechanical performance of PHBH and its storage stability are greatly improved. Therefore, this work provides a simple and efficient way to improve the crystallization and mechanical performance of PHBH, which is expected to be applied to industrial production on a large scale.

Molecular Sizes and Antibacterial Performance Relationships of Flexible Ionic Liquid Derivatives.

Cationic agents, such as ionic liquids (ILs)-based species, have broad-spectrum antibacterial activities. However, the antibacterial mechanisms lack systematic and molecular-level research, especially for Gram-negative bacteria, which have highly organized membrane structures. Here, we designed a series of flexible fluorescent diketopyrrolopyrrole-based ionic liquid derivatives (ILDs) with various molecular sizes (1.95-4.2 nm). The structure-antibacterial activity relationships of the ILDs against Escherichia coli (E. coli) were systematically studied thorough antibacterial tests, fluorescent tracing, morphology analysis, molecular biology, and molecular dynamics (MD) simulations. ILD-6, with a relatively small molecular size, could penetrate through the bacterial membrane, leading to membrane thinning and intracellular activities. ILD-6 showed fast and efficient antimicrobial activity. With the increase of molecular sizes, the corresponding ILDs were proven to intercalate into the bacterial membrane, leading to the destabilization of the lipid bilayer and further contributing to the antimicrobial activities. Moreover, the antibacterial activity of ILD-8 was limited, where the size was not large enough to introduce significant membrane disorder. Relative antibacterial experiments using another common Gram-negative bacteria, Pseudomonas aeruginosa (PAO1), further confirmed the proposed structure-antibacterial activity relationships of ILDs. More impressively, both ILD-6 and ILD-12 displayed significant in vivo therapeutic effects on the PAO1-infected rat model, while ILD-8 performed poorly, which confirmed the antibacterial mechanism of ILDs and proved their potentials for future application. This work clarifies the interactions between molecular sizes of ionic liquid-based species and Gram-negative bacteria and will provide useful guidance for the rational design of high-performance antibacterial agents.

Change of lipids in whelks (Neptunea arthritica cumingi Crosse and Neverita didyma) during cold storage.

The objective of this study was to evaluate the change of lipids in two whelk samples during cold storage. Results showed that the peroxide value (PV) and thiobarbituric acid reactive substance (TBARS) increased while the percentage of polyunsaturated fatty acid decreased, indicating that lipid oxidation occurred. The cold storage significantly reduced the levels of triacylglycerol (TAG), polar lipid (PoL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) but increased the levels of acid value (AV), free fatty acid (FFA) and monoacylglycerol, suggesting the hydrolysis of lipids. Moreover, the results showed that the lipoxygenase, acid lipase and phospholipase contributed to the hydrolysis and oxidation of lipids in the two whelks. Additionally, partial least squares discriminant analysis showed PC was positively correlated with PE, PoL and TAG, but negatively correlated with AV, FFA, PV and TBARS, indicating there is a close relationship between hydrolysis and oxidation of lipids.

Effects of proteolysis and oxidation on mechanical properties of sea cucumber (Stichopus japonicus) during thermal processing and storage and their control.

The effects of endogenous proteolysis and oxidation on mechanical properties of sea cucumber (Stichopus japonicus) during thermal processing and storage and their control were investigated. The lactic acid (LA) + tea polyphenols (TP)-treated sea cucumbers showed relatively higher values in texture and rheological indicators than the blank control group after thermal processing. By contrast, the (LA + TP)-treated sea cucumbers also had lower values in water-soluble hydroxyproline, glycosaminoglycans and proteins, trichloroacetic acid-soluble peptide content, and more orderly secondary structure of proteins, indicating that the additives affected the mechanical properties of thermally processed sea cucumbers by preventing the proteolysis of proteins. All texture and rheological indicators of thermally processed sea cucumbers decreased time-dependently during chilled storage. The additives (LA + TP) significantly prevented the progressive deterioration in mechanical properties by retarding the changes in microstructure as well as phase state and distribution of water through preventing protein oxidation.

Inhibitory effect of natural metal ion chelators on the autolysis of sea cucumber (Stichopus japonicus) and its mechanism.

Live sea cucumbers (Stichopus japonicus) were stored in a solution containing oxalic acid and tea polyphenols as natural metal ion chelators. The inhibitory effects of these chelators on the autolysis phenomenon and the underlying mechanism of action were investigated for the first time by using scanning electron microscopy, differential scanning calorimetry, low-field nuclear magnetic resonance and confocal laser scanning microscopy. External stimuli cause autolysis through the release of calcium ions (Ca2+) from cells into the extracellular connective tissue, initiating activity of the matrix metalloprotease (MMP) in the sea cucumber body wall (SCBW). MMP subsequently degrades the microfibrillar networks, that support the interconnecting collagen fibres and the interfibrillar proteoglycan bridges linking the collagen fibrils, to release the water restricted within the interspaces between collagen fibres and collagen fibrils, ultimately causing mucoid degeneration of SCBW. The natural metal ion chelators significantly inhibited the activation of MMP by chelating Ca2+, consequently effectively preventing the autolysis of SCBW.

Action of endogenous proteases on texture deterioration of the bay scallop (Argopecten irradians) adductor muscle during cold storage and its mechanism.

Texture deterioration occurs in adductor muscle of scallop (Argopecten irradians) (AMS) after 5 d of cold storage. Principal component analysis indicated the texture deterioration resulted in significant decrease of hardness, springiness, adhesiveness and chewiness, but significantly increased cohesiveness. Endogenous proteases degraded structural proteins, among which cysteine proteases were mainly responsible for myofibrillar proteins (MPs) degradation, while serine proteases degraded both MPs and connective tissue proteins. Pearson coefficient analysis showed that texture indicators significantly correlated with structural protein indicators in AMS. To be more specific, the hardness, springiness, adhesiveness and chewiness negatively correlated with myofibrillar fragmentation index, soluble hydroxyproline (Hyp) and soluble glycosaminoglycans, but positively correlated with solubility of MPs and water holding capacity. Meanwhile, the cohesiveness positively correlated with soluble Hyp. The Taylor diagram and Hierarchical cluster analysis confirmed that the inhibitors of cysteine and serine proteases could effectively retard textural deterioration of AMS during 5 d of cold storage.

Oxidation kinetics of polyunsaturated fatty acids esterified into triacylglycerols and phospholipids in dried scallop (Argopecten irradians) adductor muscles during storage.

The difference between the oxidative susceptibility of polyunsaturated fatty acids (PUFAs) esterified into triacylglycerols (TAG) and phospholipids (PL) and the effects of polyphenolic antioxidants on such susceptibility in dried seafood were investigated. Lipid fractions containing TAG and PL were extracted from dried scallops stored for various times, and their fatty acid contents were determined. The changes in contents of four representative PUFAs, including α-linolenic acid (ALA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) esterified into TAG or PL, were used to fit kinetic models to obtain the reaction rate constant (k), which reflects the oxidation rates of different lipid classes. The results indicated that the oxidation of PUFAs (ALA, AA, EPA, and DHA) esterified into TAG or PL at two storage temperatures (15 °C and 25 °C) followed the first-order kinetic model, and TAG had a greater oxidation rate than PL under the experimental conditions. The results further showed that natural phenolics could effectively inhibit the oxidation of PUFAs esterified into PL and TAG, while retaining the nutritional value of dried scallops during long term storage. Furthermore, PL could be protected by the polar polyphenolic antioxidant better than TAG. This study shows that monitoring substrate loss and using kinetic models of PUFAs esterified into different lipid classes can provide insights into further chemical and nutritional studies on food systems containing complex lipid class compositions.

Rheology-determined critical conditions for shear-induced crystallization of biosynthesized polyhydroxyalkanoates.

Shear-induced crystallization plays a crucial role in the manufacturing process of polymers. In this work, crystallization kinetics of biosynthesized polyhydroxyalkanoates (PHA) under different shear conditions were systematically investigated by rheometers. First, rheological properties of PHA melts were performed at different temperature to obtain mastercurves via the time-temperature superposition principle at 170 °C as a reference temperature. Then the stretch relaxation time and corresponding critical shear rate at different temperatures for the flow regime transition were calculated via the discrete Maxwell relaxation time spectrum and Arrhenius equation. Finally, the influence of shear temperature (Ts), shear time (ts) and shear rate (γ̇) on the crystallization process of PHA were discussed. The results showed the crystallization rate of PHA was improved significantly under high shear rate and long shear time. Interestingly, the t1/2 reached the minimum value when the γ̇ or the ts was large enough, which reached around 450 s at isothermal crystallization condition of 100 °C. Moreover, the nucleation density for PHA increased by appx.100 times than that under quiescent conditions. Therefore, this work may provide a useful theoretical guidance on the shear-induced crystallization of PHA.

Facile Surface Multi-Functionalization of Biomedical Catheters with Dual-Microcrystalline Broad-Spectrum Antibacterial Drugs and Antifouling Poly(ethylene glycol) for Effective Inhibition of Bacterial Infections.

With the development of biomedical materials, the widespread use of implantable medical devices such as biomedical catheters has saved lives and improved therapeutic outcomes in the clinic. Biomedical catheters (BCs) have the ability to connect the body inside and outside and are widely used in clinical sites for fluid discharging, blood indwelling, mechanical ventilating, and so on. However, catheter-related infections (CRIs) are common nosocomial infections with high morbidity and mortality. The pathogens in the urinary tract, blood, and lung tissue carried by BCs may be the direct cause of CRIs, and the bacterial biofilm on the surface of BCs provides a notable source of persistent diseases. Microcrystalline sulfamethoxazole (SMZ) and trimethoprim (TMP) were prepared in this study to increase both the specific surface area and water-solubility of antibacterial drugs, as well as to enhance the antibacterial and antifouling effects on the surface of BCs. As-prepared drugs and the excellent antifouling agent polyethylene glycol (PEG) were then used for the functionalization of BCs. The result indicated that the sizes of microcrystalline SMZ and TMP were 0.5-3 µm, 1-5 µm, respectively. The coating of BC-PEG-drugs exhibited excellent antibacterial efficacy in culture as well as preeminent antibacterial and antifouling abilities on the surface of BCs toward Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Moreover, the BC-PEG-drugs groups exhibited outstanding antibacterial and antifouling abilities in vivo by an animal infection model with S. aureus. This study offers a simple and effective approach for the synthesis of antibacterial and antifouling coatings that consist of microcrystalline drugs, with promising clinical applicability.

Effects of ammonium to nitrate ratio on growth, nitrogen metabolism, photosynthetic efficiency and bioactive phytochemical production of Prunella vulgaris.

CONTEXT: Prunella vulgaris L (Labiatae) is commonly used as a traditional medicinal herb in some Asian and Europe countries. To date, few studies have been conducted to determine the influence of [Formula: see text] - N/[Formula: see text] - N ratio on growth, physiological development, and bioactive phytochemical accumulation in hydroponically grown P. vulgaris. OBJECTIVE: The current study was conducted to evaluate the effect of five [Formula: see text] - N/[Formula: see text] - N ratios on growth, nitrogen metabolism, photosynthetic efficiency, and bioactive phytochemical production in P. vulgaris. MATERIALS AND METHODS: Hydroponically cultivated P. vulgaris were fertilized with five [Formula: see text] - N/[Formula: see text] - N ratios in a greenhouse for 85 d. Dried weight of root, stem, leaf and spica, leaf area, photosynthetic efficiency, activities of nitrate reductase (NR), glutamine synthetase (GS), and the concentrations of N, soluble protein, and free amino acids in the leaves, as well as the contents of rosmarinic acid (RA), ursolic acid (UA), and oleanolic acid (OA) in the spicas were measured. RESULTS: Both [Formula: see text] - N and [Formula: see text] - N as the sole source of nitrogen had inhibitory effects on P. vulgaris growth. P. vulgaris fertilized with the 25/75 ([Formula: see text] - N/NO3 - N) ratio had the highest leaf area, photosynthetic rate, and chlorophyll content. The 25/75 ([Formula: see text]/[Formula: see text]) ratio increased the spica biomass by 1828%, nitrate-reductase (NR) activity by 98%, and soluble protein concentration by 29.45% compared with the 100/0 ([Formula: see text]/[Formula: see text]) treatment. Additionally, 25 [Formula: see text] - N/75 NO3 - N resulted in the highest contents of RA and total flavonoids as well as relatively high contents of UA and OA; therefore, this ratio had the highest yield of RA, UA, OA, and total flavonoids in spicas. DISCUSSION AND CONCLUSION: The use of 25 [Formula: see text] - N/75 [Formula: see text] - N is recommended to improve biomass production and medicinal quality of P. vulgaris.