Inhibition of miR-146b-5p alleviates isoprenaline-induced cardiac hypertrophy via regulating DFCP1.

Pathological cardiac hypertrophy often precedes heart failure due to various stimuli, yet effective clinical interventions remain limited. Recently, microRNAs (miRNAs) have been identified as critical regulators of cardiovascular development. In this study, we investigated the role of miR-146b-5p and its underlying mechanisms of action in cardiac hypertrophy. Isoprenaline (ISO) treatment induced significant hypertrophy and markedly enhanced the expression of miR-146b-5p in cultured neonatal rat cardiomyocytes and hearts of C57BL/6 mice. Transfection with the miR-146b-5p mimic led to cardiomyocyte hypertrophy accompanied by autophagy inhibition. Conversely, miR-146b-5p inhibition significantly alleviated ISO-induced autophagy depression, thereby mitigating cardiac hypertrophy both in vitro and in vivo. Our results showed that the autophagy-related mediator double FYVE domain-containing protein 1 (DFCP1) is a target of miR-146b-5p. MiR-146b-5p blocked autophagic flux in cardiomyocytes by suppressing DFCP1, thus contributing to hypertrophy. These findings revealed that miR-146b-5p is a potential regulator of autophagy associated with the onset of cardiac hypertrophy, suggesting a possible therapeutic strategy involving the inhibition of miR-146b-5p.

Vitexin-rhamnoside encapsulated with zein-pectin nanoparticles relieved high-fat diet induced lipid metabolism disorders in mice by altering the gut microbiota.

This study aimed to investigate the modulatory effects of Vitexin-rhamnoside (VR) and Zein-VR-pectin nanoparticles (VRN) on lipid metabolism disorders induced by high-fat diet (HFD). The ingestion of VR or VRN attenuated dyslipidemia and fat accumulation in HFD mice, and improved intestinal dysbiosis by regulating the relative abundance of dominant bacteria, alleviating chronic inflammation and hepatic injury in HFD mice. The intervention effect of VRN was significantly higher than that of VR. After fecal microbiota transplantation (FMT) treatment, the fecal microbiota of VRN-treated donor mice significantly attenuated the symptoms associated with hyperlipidemia, confirming that VRN ameliorates HFD-induced disorders of lipid metabolism by modulating the gut microbiota, especially increasing the abundance of Rombousia and Faecalibaculum. Overall, VRN can regulate the gut microbiota and thus improve lipid metabolism. The present study provided new evidence that nanoparticles enhance the bioavailability of food bioactive ingredients.

Distinctions in structure, rheology, antioxidation, and α-glucosidase inhibitory activity of ß-glucans from different species.

To investigate the distinctions between ß-glucans from different species, Lentinula edodes ß-glucan (LG), yeast ß-glucan (YG), and oat ß-glucan (OG) were extracted with hot water and determined as ß-d-glucopyranose form by HPLC and FT-IR analysis. The molecular weight (Mw) of LG, YG, and OG was 670 kDa, 341 kDa, and 66 kDa, respectively. Scanning electron microscopy exhibited different micro surfaces of three ß-glucans and the relative crystallinity of YG was the highest (29.8 %), followed by that of LG (23.2 %) and OG (20.3 %) determined by X-ray diffraction. Congo red analysis and atomic force microscopy showed that LG and YG have triple helical structures. The apparent viscosity, storage modulus (G'), and loss modulus (G") of ß-glucans were increased with the increase of Mw. DPPH·, ABTS+·, HO·, and reducing power assays showed that ß-glucans from different species exhibited different antioxidant activities, and the DPPH· scavenging rate of 2 mg/mL LG reached >80 % higher than that of YG and OG. The α-glucosidase inhibitory activity of OG was better than YG and LG. In summary, ß-glucans from different species have different structures, physicochemical properties, and physiological functions, which provides theoretical evidence for the precise processing and utilization of ß-glucan.

Injectable catechin-based supramolecular hydrogel for highly efficient application in HPV-associated OSCC.

Catechins are a group of natural polyphenols extracted from green tea. Notably, they have been proven to have excellent anti-HPV and anti-tumour properties and to be effective against some HPV-related diseases, showing great potential in the treatment of HPV-associated oral squamous cell carcinoma (HPV+ OSCC). However, the poor bioavailability, short half-lives, and stability issues of catechins hamper their clinical application. To overcome these shortcomings of catechins, we innovatively synthesised an injectable supramolecular hydrogel, namely catechin-phenylenebisboronic acid-isoguanosine (CPBisoG), with catechin (one of the simplest catechins) and isoguanosine (isoG), another natural product with self-assembly ability, via dynamic phenylborate diester bonds. The biodegradation and sustained-release time of the CPBisoG hydrogel in mice lasted up to 72 h. This supramolecular hydrogel not only functioned as a good local drug delivery platform with good stability, injectability, self-healing properties, biocompatibility, biodegradability, but also exhibited therapeutic effects toward HPV+ OSCC in vitro and in vivo. And interestingly, it also showed selective inhibition against HPV+ OSCC cells. In all, these results demonstrate that this catechin-based hydrogel could sustainedly and highly effectively treat HPV+ OSCC topically, which could also provide a promising strategy for the management of other HPV-associated diseases in the future.

DLBLS_SS: protein secondary structure prediction using deep learning and broad learning system.

Protein secondary structure prediction (PSSP) is not only beneficial to the study of protein structure and function but also to the development of drugs. As a challenging task in computational biology, experimental methods for PSSP are time-consuming and expensive. In this paper, we propose a novel PSSP model DLBLS_SS based on deep learning and broad learning system (BLS) to predict 3-state and 8-state secondary structure. We first use a bidirectional long short-term memory (BLSTM) network to extract global features in residue sequences. Then, our proposed SEBTCN based on temporal convolutional networks (TCN) and channel attention can capture bidirectional key long-range dependencies in sequences. We also use BLS to rapidly optimize fused features while further capturing local interactions between residues. We conduct extensive experiments on public test sets including CASP10, CASP11, CASP12, CASP13, CASP14 and CB513 to evaluate the performance of the model. Experimental results show that our model exhibits better 3-state and 8-state PSSP performance compared to five state-of-the-art models.

Guanosine-based Hydrogel Integrating Photothermal Effect of PDA-AuNPs through Dynamic Borate Bond for Photothermal Therapy of Cancer.

Photothermal therapy (PTT) has drawn extensive attention owing to its noninvasive and great tissue penetration depth. However, the physical encapsulation of photothermal agents may lead to their rapid release. Dual-functional hydrogel systems that integrate functions and carriers can potentially solve this problem. In this work, we successfully developed a dual-functional guanosine(G)-based hydrogel integrating the photothermal effect and localized delivery by introducing dynamic borate ester utilizing the photothermal property of PDA-AuNPs and the self-assembly ability of G. Both in vitro and in vivo results confirmed that the GBPA hydrogel not only exhibited excellent photothermal toxicity, stability, injectability, and biocompatibility, but also possessed high photothermal antitumor activity. These results suggested that the GBPA hydrogel could be used as a dual-functional hydrogel integrating photothermal effect and localized delivery in one system, which would possibly provide a new opportunity for the design of new dual-functional hydrogels for highly efficient cancer therapy.

Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma.

Cisplatin (DDP) is a first-line chemotherapeutic drug applied for the treatment of oral squamous cell carcinoma (OSCC). The anticancer activity of DDP is tightly linked to its intracellular uptake. It is unwise to increase the DDP intake by increasing the dose or shortening the dosing interval because of the severe systemic toxicity (nephrotoxicity, ototoxicity and neurotoxicity) in DDP application. The main uptake pathways of DDP include passive diffusion and active transporter transport. Therefore, finding additional uptake pathways that can improve the effective intracellular concentration of DDP is critical. Macropinocytosis, an endocytic mechanism for extracellular material absorption, contributes to the intracellular uptake of anticancer drugs. No research has been conducted to determine whether macropinocytosis can augment the intracellular uptake of DDP in OSCC cells or not. Based on that, we proved for the first time that silmitasertib (previously CX-4945) could trigger macropinocytosis, which may increase the intracellular uptake of DDP and enhance apoptosis via in vivo and in vitro experiments. We hope that our findings will inspire a new approach for the application of DDP in cancer treatment.

Multifunctional Gold Nanoparticles: A Novel Nanomaterial for Various Medical Applications and Biological Activities.

Nanotechnology has become a trending area in science and has made great advances with the development of functional, engineered nanoparticles. Various metal nanoparticles have been widely exploited for a wide range of medical applications. Among them, gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence and are highly remarkable. AuNPs, with their multiple, unique functional properties, and easy of synthesis, have attracted extensive attention. Their intrinsic features (optics, electronics, and physicochemical characteristics) can be altered by changing the characterization of the nanoparticles, such as shape, size and aspect ratio. They can be applied to a wide range of medical applications, including drug and gene delivery, photothermal therapy (PTT), photodynamic therapy (PDT) and radiation therapy (RT), diagnosis, X-ray imaging, computed tomography (CT) and other biological activities. However, to the best of our knowledge, there is no comprehensive review that summarized the applications of AuNPs in the medical field. Therefore, in this article we systematically review the methods of synthesis, the modification and characterization techniques of AuNPs, medical applications, and some biological activities of AuNPs, to provide a reference for future studies.

Formation and disappearance of aldehydes during simulated gastrointestinal digestion of fried clams.

The formation and disappearance of aldehydes during simulated gastrointestinal digestion (SD) of fried clams was investigated in order to shed light on the underlying mechanism. Results from the thiobarbituric acid reactive substance (TBARS) and fluorometric assays using a specific aldehyde probe indicated that the SD (with lipase) of fried clams initially reduced (at the gastric stage), but subsequently increased (mainly at the intestinal stage) the contents of total aldehydes. Meanwhile, eight specific aldehydes including propanal, acrolein, trans-2-pentenal, hexanal, trans,trans-2,4-octadienal, trans,trans-2,4-decadienal, 4-hydroxy-hexenal and 4-hydroxy-nonenal in the digested meal were determined by using a high-performance liquid chromatography-tandem electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) method. Results indicated that the changes in the trend of the contents of the eight aforementioned aldehydes were similar to those of total aldehydes during SD (with lipase) of fried clams. However, a similar SD process without lipase time-dependently reduced the contents of total and individual aldehydes. Moreover, lipid classes and free fatty acids (FFAs) in the digested meal were determined to reveal the degree of hydrolysis of lipids during the SD process. Results indicated that the SD (with lipase) of fried clams significantly hydrolyzed triacylglycerols (TAG) and polar lipids (PL) and produced FFAs, but the SD process without lipase resulted in negligible lipid hydrolysis. Thus, our results demonstrated a positive correlation between lipid hydrolysis and aldehyde generation during the SD of fried clams. Alternatively, unsaturated FFAs instead of TAG and PL could have served as the main precursors for aldehyde generation due to their high oxidative susceptibility.

Preparation and characterization of highly lipophilic modified potato starch by ultrasound and freeze-thaw treatments.

In order to explore the potential application of combined physical treatment in producing highly lipophilic modified starch, the effects of ultrasound combined with freeze-thaw treatment on the microstructure and physicochemical properties of potato starch were investigated. The samples treated by combined treatment had the roughest structure and the oil adsorptive capacity value increased from 59.62% (native starch, NS) to 80.2% (7 cycles of ultrasound-freeze-thaw treatment starch, 7UT-FTS). Compared to NS, the crystalline type and chemical groups of modified starches did not change, but the relative crystallinity, enthalpy change, and paste viscosity decreased to varying degrees, while the gelatinization temperature increased. The digestibility of raw modified starch was higher than that of NS, but this phenomenon disappeared after gelatinization. 7UT-FTS showed better resist-digestibility than NS after encapsulating oil. Hence, this would be an efficient and environmentally friendly way to produce modified starch with safety, highly lipophilic and heat resistance.

Effects of temperature and heating time on the formation of aldehydes during the frying process of clam assessed by an HPLC-MS/MS method.

This study aimed at investigating the formation and accumulation of 16 reactive aldehydes in clam (Ruditapes philippinarum) during oil frying in both the tissue and the oil using an HPLC-ESI-MS/MS methodology. After processing, the accumulation of acrolein, crotonaldehyde, pentanal, trans-2-hexenal, hexanal, trans, trans-2,4-heptadienal, heptanal, nonanal, trans, trans-2,4-decadienal and 4-hydroxy-2-nonenal was most noticeable in both fried clam and frying oil. Most of the aldehyde species showed a time- and temperature-dependent manner of formation and accumulation during frying due to continuous oxidative degradation under conditions employed. However, several species of aldehyde such as acrolein and trans-2-pentenal slightly decreased at higher temperatures and/or longer frying times, which may be due to the imbalance toward disappearance of aldehydes resulting from their evaporation under the extreme conditions. Presence of natural polyphenols in bamboo leaves significantly prevented the formation of aldehydes in both fried clam and frying oil due to their antioxidant activity (P < 0.05).

Stability of resveratrol esters with caprylic acid during simulated in vitro gastrointestinal digestion.

Lipophenols, esterified phenols with fatty acids, have attracted increasing attention because of their better protective effects in lipid-based food matrices from oxidation. However, little is known about their digestion. In this study, the digestive stability of resveratrol (RSV) esters with caprylic acid (RCAPs) in a model gastrointestinal digestion system was evaluated. The results demonstrated that RCAPs were relatively stable without hydrolysis in mouth and gastric phases. However, in the intestinal phase, pancreatic lipase rather than phospholipase A2 could hydrolyze monoester and diesters to free RSV. After 120 min of incubation at 37 °C, 53.68% of monoester and 11.36% of diesters were hydrolyzed. However, no hydrolysis of the triester was noticed. Obviously, the level of hydrolysis of RCAPs was negatively correlated with the degree of substitution. Therefore, it was speculated that RSV in fatty acid ester forms could partially be absorbed by intestinal lumen in the form of free RSV.

Hydrolysis and Transport Characteristics of Tyrosol Acyl Esters in Rat Intestine.

Lipophenols such as palmitoyl esters of green-tea polyphenols (GTP) have been allowed for use as food additives for oxidation control. However, their digestive absorption remains unexplored. In this paper, the hydrolysis and transport characteristics of tyrosol acyl esters (TYr-Es) with various fatty acids (C12:0, C14:0, C16:0, C18:0, C18:1, and C18:2) were evaluated using the everted-rat-gut-sac model for the first time. HPLC-UV measurements demonstrated that TYr-Es were hydrolyzed to TYr, which contributed significantly to TYr transport across the sacs. The hydrolysis and transport rates correlated negatively with the chain lengths of their lipid moieties but showed a positive correlation with the degree of unsaturation. In general, all TYr-Es exhibited sustained-release behavior; therefore, the production of TYr-Es may serve as a useful way to prolong the duration of action and further improve the bioactivities of TYr.

Evaluation of the stability of tyrosol esters during in vitro gastrointestinal digestion.

Lipophenols such as tea polyphenol palmitate derivatives (palmitoyl esters of tea polyphenols) have been classified as non-toxic food additives due to their better protective effects on lipidic food matrices from oxidation, but their digestion and absorption have remained unexplored. In this study, the digestive stability of tyrosol acyl esters (TYr-Es) with fatty acids of different chain lengths and different degrees of unsaturation such as C12:0, C14:0, C16:0, C18:0, C18:1, C18:2, and C22:6 was evaluated using an in vitro simulated gastrointestinal tract model containing various digestive enzymes (pancreatin, pancreatic lipase and phospholipase A2). HPLC-UV measurements demonstrated that only pancreatin and pancreatic lipase, but not phospholipase A2, could hydrolyze TYr-Es to free TYr. The degree of TYr-E hydrolysis negatively correlated with the chain length but positively correlated with the degree of unsaturation of their lipid moiety. In addition, the fact that TYr in fatty acid ester forms could be absorbed by the intestinal lumen, at least partially in the form of free TYr, may explain a sustained release behavior of TYr-Es to TYr during the time-course following the digestion process.

Changes in Lipid Profiles of Dried Clams ( Mactra chinensis Philippi and Ruditapes philippinarum) during Accelerated Storage and Prediction of Shelf Life.

To predict the shelf life through an Arrhenius model and evaluate the changes in lipid profiles, two types of dried clams were stored at 50 and 65 °C and collected periodically for analysis. The predicted shelf life values of the two dried clam samples were 530 ± 14 and 487 ± 24 h (24 °C), and the relative errors between the actual and predicted values were 5.7 and 6.8%, respectively. During accelerated storage, the peroxide value, p-anisidine value, thiobarbituric acid-reactive substances value, total oxidation value, acid value, and free fatty acid content all increased, while the levels of triacylglycerol, phosphatidylcholine, phosphatidylethanolamine, major glycerophospholipid molecular species, and polyunsaturated fatty acid (PUFA) decreased. Moreover, content of phospholipid containing PUFA decreased significantly than that of triacylglycerol containing PUFA. Results indicated that the Arrhenius model was suitable for the shelf life prediction of dried clams and accelerated storage caused loss in quality of dried clams in terms of lipids.

Characterization of lipids in three species of sea urchin.

Sea urchin gonad has been regarded as a "healthy" food. Although previous studies have suggested that sea urchin gonad might serve as a potential rich source of long chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFA) enriched phospholipid (PL), the molecular species profile of its PL has rarely been reported. In this study, about 200 molecular species of glycerophospholipid (GP), including glycerophosphocholine, glycerophosphoethanolamine, glycerophosphoserine, glycerophosphoinositol, lysoglycerophosphocholine and lysoglycerophosphoethanolamine, in gonads from three species of sea urchin (Glyptocidaris crenularis, Strongylocentrotus intermedius and Strongylocentrotus nudus) were characterized using tandem mass spectrometry. Most of the predominant GP molecular species contained PUFA, especially eicosapentaenoic acid (EPA). Meanwhile, the sea urchin lipids contained a high proportion of PL (39.45-50.30% of total lipids) and PUFA (34.47-46.56% of total FA). Among PL, phosphatidylcholine (67.88-72.58mol%) was dominant. Considering the high level of PUFA enriched GP, sea urchin gonads provide great potential as health-promoting food for human consumption.

Lipid profiles in different parts of two species of scallops (Chlamys farreri and Patinopecten yessoensis).

Different classes of lipids and phospholipids (PL) as well as fatty acid (FA) compositions, and glycerophospholipid (GP) molecular species in edible parts (adductor muscles) and by-products (gonads and mantles) of scallops Patinopecten yessoensis and Chlamys farreri were characterized. The lipids contained high levels of polyunsaturated FA (PUFA) (20.44-58.81% of total FAs) and PL (54.99-78.26% of total lipids). Among PL, phosphatidylcholine (41.39-51.86 mol%) was dominant. More than 230 GP species belonging to glycerophosphocholine, glycerophosphoethanolamine, glycerophosphoserine, glycerophosphoinositol, lysoglycerophosphocholine, lysoglycerophosphoethanolamine and lysoglycerophosphoinositol were characterized. Individual GP molecular species in different body parts of scallops were also partially quantified. Most of the dominant GP species contained PUFA, especially eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Considering the high level of PUFA enriched GP, edible parts and by-products (gonads and mantles) of scallops Patinopecten yessoensis and Chlamys farreri provide great potential as health-promoting food for human consumption.

Effect of high hydrostatic pressure and retrogradation treatments on structural and physicochemical properties of waxy wheat starch.

In this study, the effects of high hydrostatic pressure and retrogradation (HHPR) treatments on in vitro digestibility, structural and physicochemical properties of waxy wheat starch were investigated. The waxy wheat starch slurries (10%, w/v) were treated with high hydrostatic pressures of 300, 400, 500, 600MPa at 20°C for 30min, respectively, and then retrograded at 4°C for 4d. The results indicated that the content of slowly digestible starch (SDS) in HHPR-treated starch samples increased with increasing pressure level, and it reached the maximum (31.12%) at 600MPa. HHPR treatment decreased the gelatinization temperatures, the gelatinization enthalpy, the relative crystallinity and the peak viscosity of the starch samples. Moreover, HHPR treatment destroyed the surface and interior structures of starch granules. These results suggest that the in vitro digestibility, physicochemical, and structural properties of waxy wheat starch are effectively modified by HHPR.

Characterization of glycerophospholipid molecular species in six species of edible clams by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

The molecular species of glycerophosphocholine (GPCho), glycerophosphoethanolamine (GPEtn), glycerophosphoserine (GPSer), lysoglycerophosphocholine (LGPCho) and lysoglycerophosphoethanolamine (LGPEtn) from six species of edible clams were characterized by using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. At least 435, 453, 468, 443, 427 and 444 glycerophospholipid (GP) molecular species were characterized, respectively, from Cyclina sinensis, Mactra chinensis Philippi, Mactra veneriformis Reeve, Meretrix meretrix, Ruditapes philippinarum and Saxidomus purpurata. Most of the predominant GP molecular species in clam contained polyunsaturated fatty acids (PUFA), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), indicating that clam is a potential resource of GP enriched PUFA. According to the amount of the major molecular species containing EPA and DHA, Cyclina sinensis was the best fit species for GPCho, Mactra veneriformis Reeve was the best fit species for GPEtn, Mactra chinensis Philippi was the best fit species for GPSer and LGPEtn, and Saxidomus purpurata was the best fit species for LGPCho.

Identification of glycerophospholipid molecular species of mussel (Mytilus edulis) lipids by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

This study was carried out to identify the glycerophosphocholine (GPCho), glycerophosphoethanolamine (GPEtn) and glycerophosphoserine (GPSer) compositions in lipids extracted from mussels using Folch, Bligh-Dyer and methyl-tert-butyl ether (MTBE) methods by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). The molecular species of GPCho, GPEtn and GPSer were characterized according to the MS and MS/MS information. A semi-quantitative method using internal standard was established to compare the difference in glycerophospholipids (GP) between samples recovered with different methods. At least 212, 230 and 206 GP species were identified, respectively, from lipids recovered by Folch, Bligh-Dyer and MTBE methods. Most of the abundant GP species in mussels contained EPA and DHA. Some GP species with low content were not present in lipids recovered by the Folch and MTBE methods when compared with that recovered by the Bligh-Dyer method. However, for most GP species in lipids recovered by different methods, no quantitative differences existed.