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In this study, RAW 264.7 cells and immunosuppressive models were used to investigate the immunostimulatory activity of tilapia-head chondroitin sulfate (CS) through in vitro and in vivo experiments. The results showed that tilapia-head chondroitin sulfate (CS) could induce the produce of NO, IL-1β, IL-6, IL-10 and TNF-α in RAW 264.7 cells. Cyclophosphamide (CTX) induced thymic atrophy in mice (thymic index 0.11%±0.01%), while thymic index was significantly up-regulated by low-dose CS (thymic index (0.17%±0.03%) and high-dose CS (thymic index (0.18%±0.02%) interventions (P

Abstract Image steganography aims to hide secret data in the cover media for covert communication. Though many deep‐learning‐based image steganography methods have been presented, these approaches suffer from the inefficiency of building long‐distance connections between the cover and secret images, leading to noticeable modification traces and poor steganalysis resistance. To improve the visual imperceptibility of generated stego images, it is essential to establish a global correlation between the cover and secret images. In this way, the secret image can be dispersed throughout the cover image globally. To bridge this gap, a novel image steganography framework called HiiT is proposed, which takes advantage of CNN and Transformer to learn both the local and global pixel correlation in image hiding. Specifically, a new Transformer structure called Inception Transformer is proposed, which incorporates the Inception Net in the attention‐based Transformer architecture. The Inception Net can learn different scaled image features using multiple convolution kernels, while the attention mechanism can learn the global pixel correlation. By this, the proposed Inception Transformer learns the long‐distance pixel dependency between the cover and secret images. Furthermore, we propose a ‘Skip Connection’ mechanism in the proposed Inception Transformer, which merges the low‐level visual features and high‐level semantic features and achieves better model performance. In detail, The HiiT generates higher‐quality stego images with 45.46 PSNR and 0.9915 SSIM. Besides, accurately restored secret images achieve 47.27 PSNR and 0.9952 SSIM. Extensive experimental results show the proposed HiiT significantly improves the image‐hiding performance compared with state‐of‐the‐art methods.

Abstract Image steganography is the art of concealing secret information within images to prevent detection. In deep‐learning‐based image steganography, a common practice is to fuse the secret image with the cover image to directly generate the stego image. However, not all features are equally critical for data hiding, and some insignificant ones may lead to the appearance of residual artifacts in the stego image. In this article, a novel network architecture for image steganography with hybrid attention mechanism based on generative adversarial network is introduced. This model consists of three subnetworks: a generator for generate stego images, an extractor for extracting the secret images, and a discriminator to simulate the detection process, which aids the generator in producing more realistic stego images. A specific hybrid attention mechanism (HAM) module is designed that effectively fuses information across channel and spatial domains, facilitating adaptive feature refinement within deep image representations. The experimental results suggest that the HAM module not only enhances the image quality during both the steganography and extraction processes but also improves the model's undetectability. Stego images are mixed with varying levels of noise in the training process, which can further improve robustness. Finally, it is verified that the model outperforms current steganography approaches on three datasets and exhibits good undetectability.

IntroductionCarrageenan oligosaccharides are of significant interest due to their diverse bioactivities, necessitating efficient methods for their production. To this day, the discovery and isolation of microorganisms capable of effectively degrading carrageenan is still crucial for the production of carrageenan oligosaccharides. In addition, there are no current reports of bacteria of the genus Photobacterium capable of secreting κ-carrageenanase or degrading carrageenan.MethodsIn the current study, strain GDSX-4 was obtained from Gracilaria coronopifolia after enrichment culture, primary screening and rescreening and was initially characterized by morphology and 16SrDNA. The pure culture of strain GDSX-4 was further subjected to bacterial genome sequencing assembly and bioinformatic analysis. Specifically, homology group cluster (COG) annotation, CAZy (carbohydrate-active enzyme) database annotation and CAZyme genome clusters (CGCs) annotation were utilized to identify potential polysaccharide degradation functions. Enzymatic activity was assessed under different conditions, including substrate, temperature, pH, and the presence of metal ions. Hydrolysis products were analyzed using thin-layer chromatography (TLC) and electrospray ionization mass spectrometry (ESI-MS).ResultsPhotobacterium rosenbergii GDSX-4 is a Gram-negative bacterium isolated from the red algae, capable of degrading several polysaccharides. The draft genome was predicted to have 6,407,375 bp, 47.55% G+C content and 6,749 genes. Among them, 214 genes encoding carbohydrate enzymes were annotated, including carrageenase, agarose, alginate lyase, and chitinase. GDSX-4 exhibited remarkable carrageenan-degrading activity, with a specific enzyme activity of 46.94 U/mg. Optimal hydrolysis conditions were determined to be 40°C and pH 7.0, with the enzyme retaining 80% of its activity below 30°C and across a pH range of 4.0–10.0. Metal ions such as as K+, Na+, and Ba2+ enhanced enzymatic activity, while Ni2+, Mn2+, and Cu2+ had inhibitory effects. kappa-carrageenan was totally hydrolyzed into oligosaccharides with degrees of polymerization ranging from 2 to 6.DiscussionThese findings highlight the potential of GDSX-4 for the efficient production of carrageenan oligosaccharides, paving the way for applications in the food and agricultural industries. Future studies may focus on the efficient expression of κ-carrageenase and expand its industrial application in the preparation of oligosaccharides.

ObjectiveTo investigate whether progesterone levels on the human chorionic gonadotropin (hCG) trigger day are associated with clinical outcomes in fresh cycles and the first frozen–thawed cycles (the freeze-all strategy) following the transfer of a high-quality single blastocyst.MethodsThis single-center retrospective analysis was conducted on patients undergoing in vitro fertilization with the gonadotropin-releasing hormone (GnRH) antagonist protocol from January 2017 to December 2023. The study included the first and second oocyte retrieval cycles with progesterone levels ≤2 ng/ml on hCG trigger day. Clinical pregnancy rates and early miscarriage rates were compared among groups using curve fitting, threshold effect analysis, and multivariable regression.ResultsWhen progesterone levels were between 1 and 2 ng/ml, the pregnancy rate in fresh cycles was only 51% of that in cycles with progesterone levels ≤1 ng/ml (95% CI: 0.33, 0.79, p = 0.0028). And the pregnancy rate decreased by 25% (95% CI: 0.51, 1.09) for frozen cycles, although there was no statistically significant (p = 0.1273). When cycle types were used as a binary variable in multivariate regression analysis, it was found that the clinical pregnancy rate in frozen cycles was 1.84 times higher than in fresh cycles (OR = 1.84, 95% CI: 1.38–2.47). For progesterone levels between 1 and 2 ng/ml, the clinical pregnancy rate in frozen cycles was 2.90 times that of fresh cycles (OR = 2.90, 95% CI: 1.59, 5.29, p = 0.0015). Progesterone levels on hCG day had no impact on the clinical pregnancy rate in thaw cycles, nor did they affect miscarriage rates in fresh or thaw cycles (p > 0.05).ConclusionWhen progesterone levels on hCG trigger day were between 1 and 2 ng/ml, the clinical pregnancy rate for frozen–thawed cycles of high-quality single blastocyst transfer using an GnRH antagonist protocol significantly surpasses that of fresh cycles, thus elective frozen embryo transfer after the freeze-all strategy is recommended.

Objective: In this work, the optimal preparation process parameters of selenium-curcumin nanoparticles (SeNPs@Cur) were explored and its protective effect on alcoholic liver injury was evaluated. Methods: On the basis of single factor experiment, with particle size as the index, curcumin dosage, molar ratio of VC to Na2SeO3, reaction time and reaction temperature were selected as influence factors. The process parameters of SeNPs@Cur were optimized by response surface methodology, and its structure was characterized by scanning electron microscope (SEM), fourier transform infrared spectrometer (FT-IR) and energy dispersive spectrometer (EDS). The protective effect of SeNPs@Cur on ethanol-induced LO2 cell injury was investigated by MTT method. Results: The optimal conditions of SeNPs@Cur were list as follows: Curcumin dosage of 5.92 mg/mL, molar ratio of VC to Na2SeO3 of 10.39:1, the reaction time of 1.98 h, and the reaction temperature of 34.00 ℃. Under these conditions, the SeNPs@Cur with a minimum size of (100.79±3.46) nm was obtained. The loading rate of curcumin and the selenium content in the sample were 12.80%±0.80% and 23.32%±0.07%, respectively. Further structural identification showed that the prepared SeNPs@Cur was dispersed spherical nanoparticles. Moreover, compared with the model group, after treatments with different dosages of SeNPs@Cur, the cell viabilities increased from 58.06%±0.43% to 71.43%±1.39%, 77.33%±3.54%, and 85.41%±4.61%, respectively, indicating that SeNPs@Cur had a protective effect on LO2 cells damaged by ethanol in a concentration-dependent manner. Conclusion: The SeNPs@Cur with anti-alcoholic liver injury effect was successfully obtained, which provided new technical means and theoretical reference data for formulation improvement and application of curcumin.

Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate (SeCS) through the redox reaction of ascorbic acid (Vc) and sodium selenite (Na2SeO3) and we found that SeCS could inhibit tumor cell proliferation and invasion. However, its effect on angiogenesis and its underlying mechanism are unknown. In this study, we analyzed the effect of SeCS on tube formation in vitro, based on the inhibition of tube formation and migration of human umbilical vein endothelial cells (HUVECs), and evaluated the in vivo angiogenic effect of SeCS using the chick embryo chorioallantoic membrane (CAM) assay. The results showed that SeCS significantly inhibited the angiogenesis of chicken embryo urothelium. Further mechanism analysis showed that SeCS had a strong inhibitory effect on VEGFR2 expression and its downstream PI3K/Akt signaling pathway, which contributed to its anti-angiogenic effects. In summary, SeCS showed good anti-angiogenic effects in an HUVEC cell model and a CAM model, suggesting that it may be a potential angiogenesis inhibitor.

Background: Bacterial infections are a major challenge in food processing and public health, and there is an urgent need to develop novel antimicrobial agents. Objectives: The purpose of this study is to investigate the potential mechanism and key components of Pinctada martensii antimicrobial proteins (Pm-Aps) to provide a theoretical basis for the development of novel antimicrobial agents. Methods: The researchers used Vibrio parahaemolyticus (VP) to stimulate Pinctada martensii, extracted the antimicrobial proteins, and analyzed their antimicrobial activities, potential mechanisms of action, and key components using proteomics. Results: The results showed that the antimicrobial activity of Pm-Aps, with broad-spectrum antimicrobial effects, was significantly enhanced after VP stimulation. This was associated with the upregulation of LAAO, CHDH, TLR2, ATG16L1, BAK, CLCA4, and CASP8 and the downregulation of MCM3, MCM5, DTYMK, PLK1, FBXO6, LPCAT3, GST, LAMTOR5, CYP17A, CTSA, and RRM1. It is hypothesized that these proteins may inhibit bacterial growth and multiplication by activating immune-related signaling pathways, inhibiting DNA replication and repair, and inducing apoptosis and autophagy. Furthermore, it was found that LAAO may be a key component of the antimicrobial action of Pm-Aps, killing bacteria by catalyzing the oxidation of amino acids to produce hydrogen peroxide (H2O2). Conclusions: These results strongly suggest that Pm-Aps is an effective antimicrobial protein, and it is expected that new LAAO can be obtained from Pm-Aps.

To accurately, efficiently, and environmentally prepare carrageenan oligosaccharides, we have developed a method that uses H2O2 and TiO2 as catalysts for the photodegradation of κ-carrageenan (KC). The photodegradation of KC was monitored using various amounts of TiO2 and H2O2 and different concentrations of KC via HPLC and it could decrease the average molecular weight of KC into 1.6 kDa within 2 h. Further research under optimal conditions. As a control, the effects of UV, UV/H2O2, UV/TiO2, and H2O2/TiO2 treatments were studied. In contrast, UV/H2O2/TiO2 treatments showed a coordinated effect. The effect of degradation on the structure of KC was investigated by FT-IR, XRD, and there was no obvious remotion of sulfate groups. Furthermore, oral administration of KCO prolonged the healthy lifespan of nematodes induced by ultraviolet stress and significantly regulated oxidative stress. This study suggests that the precise preparation and application of KCO may be beneficial.

Sea red rice bran, a new salinity-tolerant sea rice by-product, contains high levels of ceramides (Cers), which are necessary to tap into their bioactivity for improving the health effects of the organism. This study aimed to investigate the effect of Cers on the improving the oxidative stress and lifespan of C. elegans, and the relationship of the interaction through the p38/MAPK signaling pathway and under the regulation of intestinal flora. The results showed that Cers treatment effectively reversed the oxidative damage caused by paraquat and hydrogen peroxide in C. elegans and reduced overexpression of ROS and accumulation of mitochondrial membrane damage. In addition, Cers intake successfully activated all gene targets of p38/MAPK signaling pathway, significantly promoted the migration of SKN-1 to the nucleus, and increased the abundance of probiotic bacteria such as Ruminoccus, AKKermansia, and Lactobacillus in the intestinal flora and effectively mitigated the adverse effects of oxidative stress. Therefore, these results indicate that Cers could be effectively in ameliorating the level of oxidative stress in the body, thereby increasing longevity and health indicators. Providing a theoretical basis for the prevention of aging-related chronic diseases and health care, and enhancing the high-value comprehensive utilization of sea red rice by-products.

The issue of model explainability has gained significant attention in understanding the vulnerabilities and anonymous decision-making processes inherent in deep neural networks (DNN).While there has been considerable research on explainability for traditional DNN, there is a lack of exploration on the operation mechanism and explainability of reversible neural networks (RevNN).Additionally, the existing explanation methods for traditional DNN are not suitable for RevNN and suffer from issues such as excessive noise and gradient saturation.To address these limitations, a visual explanation method called visual explanation method for reversible neural network (VERN) was proposed for RevNN.VERN leverages the reversible property of RevNN and is based on the class-activation mapping mechanism.The correspondence between the feature map and the input image was explored by VERN, allowing for the mapping of classification weights of regional feature maps to the corresponding regions of the input image.The importance of each region for model decision-making was revealed through this process, which generates a basis for model decision-making.Experimental comparisons with other explanation methods on generalized datasets demonstrate that VERN achieves a more focused visual effect, surpassing suboptimal methods with up to 7.80% improvement in average drop (AD) metrics and up to 6.05% improvement in average increase (AI) metrics in recognition tasks.VERN also exhibits an 82.00% level of localization for the maximum point of the heat value.Furthermore, VERN can be applied to explain traditional DNN and exhibits good scalability, improving the performance of other methods in explaining RevNN.Furthermore, through adversarial attack analysis experiments, it is observed that adversarial attacks alter the decision basis of the model.This is reflected in the misalignment of the model’s attention regions, thereby aiding in the exploration of the operation mechanism of adversarial attacks.

Objectives: Oral insulin delivery has received much attention over the past 20 years due to its high compliance. The aim of this study is to prepare nanoparticles for the oral delivery of insulin; Methods: Fucoidan and protamine were used to prepare a pH-sensitive nanoparticle via self-assembly. The secondary structure and in vitro stability of the nanoparticles were characterized using FTIR, XRD, ITC, and TEM. the nanoparticles had a controlled release effect on insulin in simulated intestinal fluid. The pre-liminary therapeutic effect on high-fat-fed type 2 diabetic mice; Results: When the fucoidan/protamine mass ratio was 10:3 (w/w), the particle size and zeta potential were 140.83 ± 1.64 nm and −48.13 ± 0.61 mV.The encapsulation efficiency of insulin was 62.97 ± 0.59%. The preliminary therapeutic effect on type 2 diabetic mice showed that the fasting blood glucose of diabetic mice decreased from 10.28 ± 0.88 mmol/L to 9.22 ± 0.64 mmol/L, the area under the curve value of oral glucose tolerance test was reduced by 11.70%, and the insulin se-cretion of diabetic mice was increased by 13.3%; Conclusions: The nanoparticles were prepared successfully by self-assembly. The empty and insulin-loaded nanoparticles remained stable in simulated gastric fluid, and the nanoparticles had a controlled release effect on insulin in simulated intestinal fluid. Moreover, insulin-loaded nanoparticles could relieve on type 2 diabetic mice.

With the continuous increase in the penetration rate of renewable energy, the randomness and flexibility demand in the power system continues to increase. The main grid side of the power system vigorously develops pumped hydro storage (PHS) resources. However, the current PHS station scheduling method of a fixed time period and fixed power has lost a certain flexibility supply. In this paper, an optimal dispatching model of multi-pumped hydro storage stations is proposed to supply flexibility for different regions of the state grid in east China. Firstly, the credible predictable power (CPP) of renewable energy is calculated and the definition of flexibility demand of a power system is given. The calculation model for flexibility demand is established. Secondly, considering the regional allocation constraint in the state grid in east China, a non-centralized model of multi-PHS within the dispatch scope is established. In the model, the constraints of storage capacity of different hydropower conversion coefficients of each PHS station is considered. The flexibility supply model of PHS stations to each region of the state grid in east China is established to realize reasonable flexibility allocation. Then, by combining the PHS station models and the flexibility demand calculation model, the optimal dispatching model for the flexibility supply of multi-PHS stations is established. Finally, based on the network dispatching example, the effectiveness and superiority of the proposed strategy are verified by a case study.

Abstract Transfer learning is a great technology that can leverage knowledge from label-rich domains to address problems in similar domains that lack labeled data. Most previous works focus on single-source transfer, assuming the source domain contains sufficient labeled data and is close to the target domain. However, in practical applications, this assumption is hardly met, and labeled data exist in different domains. To improve the adaptability of transfer learning models for multi-source scenarios, many existing methods utilize the commonality and specificity across source domains. They either map all source domains with the target domain into a common feature space for knowledge transfer or combine multiple classifiers trained on pairs of each source and target to form a target classifier. However, the correlations across multiple source domains that can bring significant impacts on learning performance are ignored. In light of this, we propose a novel multi-source transfer learning method based on the power set framework (PSF-MSTL). First, PSF-MSTL constructs a power set framework that enables different source domains to be interrelated. Second, PSF-MSTL makes the source-domain framework integral and able to provide complementary knowledge using a dual-promotion strategy. Additionally, PSF-MSTL is formulated as an optimization problem, and an iterative algorithm is presented to address it. Finally, we conduct extensive experiments to show that PSF-MSTL can outperform many advanced multi-source transfer learning methods.

A disorder of the immune system is the fundamental cause of cancer. The body can defend against external threats only when the immune system is robust. Polysaccharides are natural immune regulators that can regulate the immune function of the body at multiple levels and targets. Recent studies have shown that polysaccharides can inhibit tumor growth by stimulating the immune system, thereby promoting immune cell proliferation, increasing cytokine secretion, and regulating the immune functions of the body as a whole. However, there are few reports on the potential mechanism by which polysaccharides inhibit tumor immune escape. Therefore, this article reviews the immune anti-tumor effect of polysaccharides, the mechanism by which they inhibit tumor immune escape, and their signaling pathways, in order to provide a theoretical basis for the development of anti-tumor drugs and malignant tumor treatment.

Abstract The International Agency for Research on Cancer has classified semimetal arsenic as a human carcinogen. Arsenic poisoning can severely impact human health. Arsenic can be classified into inorganic and organic arsenic, with arsenolipids (AsLs) belonging to the category of organic arsenic. The primary species of AsLs include arsenic‐containing hydrocarbons (AsHCs), fatty acids, and phospholipids. AsLs are highly abundant in marine organisms and diet may be the primary source of exposure to AsLs. Although increasing evidence shows that AsLs are cytotoxic to humans, the specific toxicity and its mechanism remain unclear. This study aimed to evaluate the hepatotoxicity and possible mechanisms of the toxic effects of AsLs in mice. Three AsLs (AsHC 332, AsHC 346, and AsHC 374) were administered via gavage at a dose of 3 mg/kg for 4 weeks. The results showed that short‐term exposure did not affect the normal growth and development of mice. However, it caused liver damage in mice, mainly by disrupting the metabolism of selenium, copper, zinc, and other elements related to the synthesis of antioxidant enzymes, thereby reducing the activity of antioxidant enzymes and the expression of related genes. The liver damage effect of AsHC 332 was the strongest among the three AsLs.

ObjectiveCognitive-behavioral stress management (CBSM) is a psychotherapy that helps patients cognize and manage stress to improve mental health and quality of life. This study aimed to explore the influence of CBSM on anxiety, depression, and quality of life in non-small cell lung cancer (NSCLC) patients.MethodsIn total, 172 NSCLC patients who received tumor resection were randomized 1:1 into the usual care (UC) group (N = 86) and CBSM group (N = 86) to receive 10-week UC and CBSM interventions. Moreover, all participants attended a 6-month follow-up.ResultsHospital Anxiety and Depression Scales (HADS)-anxiety score at 3rd month (M3) (P = 0.015) and 6th month (M6) (P = 0.018), HADS-depression score at M3 (P = 0.040) and M6 (P = 0.028), and depression rate at M6 (P = 0.035) were descended in CBSM group compared to UC group. Besides, depression severity was reduced at M6 (P = 0.041) in CBSM group compared to UC group, but anxiety severity only showed a decreased trend (P = 0.051). Additionally, Quality of Life Questionnaire-Core 30 (QLQ-C30) global health status score and QLQ-C30 function score at 1st month (M1), M3, and M6 were elevated (all P < 0.05), while QLQ-C30 symptoms score was declined at M1 (P = 0.031) and M3 (P = 0.014) in CBSM group compared to UC group. Notably, the efficacy of CBSM was impressive in patients with baseline depression or undergoing adjuvant therapy.ConclusionCBSM is a feasible intervention that effectively improves mental health and quality of life in postoperative NSCLC patients.

Alpinia officinarum Hance, a well known agricultural product in the Lei Zhou peninsula, is generally rich in polysaccharides. In order to enhance the use of A. officinarum Hance polysaccharides (AOP) in functional food, AOP was extracted using an ultrasonic-assisted extraction method, and the ultrasonic extraction parameters of AOP was optimized. Furthermore, this study investigated the physicochemical and antioxidant activities of AOPs. In addition, the structural properties were preliminarily determined using Fourier-transform infrared spectroscopy (FTIR), high performance size exclusion chromatography, and a Zetasizer. Ultimately, this study explored the mechanism underlying the antioxidant activities of AOP. The results showed that the optimal ultrasonic-assisted extraction parameters were as follows: ultrasonic time, 6 min; ratio of water to material, 12 mL/g; and ultrasonic power, 380 W. Under these conditions, the maximum yield of AOPs was 5.72%, indicating that ultrasonic-assisted extraction technology is suitable for extracting AOPs due to the reduced time and water usage. Additionally, AOPs were purified using graded alcohol precipitation, resulting in three fractions (AOP30, AOP50, and AOP70). AOP30 had the lowest molecular weight of 11.07 kDa and mainly consisted of glucose (89.88%). The half inhibitory concentration (IC50) value of AOP30 and AOP70 was lower than that of AOP50 in the ability to scavenge the ABTS radical, while a reverse trend was observed in reducing ferric ions. Notably, the antioxidant activities of AOPs were highly correlated with their polydispersity index (Mw/Mn) and Zeta potential. AOP30, a negatively charged acidic polysaccharide fraction, exhibited electron donating capacities. Additionally, it displayed strong antioxidant abilities through scavenging 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radicals and reducing ferric ions. In conclusion, the present study suggests that AOP30 could be developed as an antioxidant ingredient for the food industry.

Heparinoid, a sulfate polysaccharide derived from marine organisms was attracted largely attention due to its versatile activities. A naturally occurring heparinoid (M2) that was extracted from the mollusk Meretrix lusoria and used in this investigation shown strong antithrombotic action. UV–Vis, FT-IR, SAX-HPLC, and NMR were used to explore the structural characteristics of M2, results indicated that M2 similar with heparin, its average molecular weight was 22.58 kDa. Which was primarily made up of→4)-α-IdoA2S-(1→4)-α-GlcNS6S-(1→ (31.19%), →4)-β-GlcA-(1→4)-α-GlcNAc (1→ (23.21%), →4)-β-GlcA-(1→4)-α-GlcNS (1→ (13.87%), →4)-α-IdoA2S-(1→4)-α-GlcNS (1→ (8.95%), →4)-β-GlcA-(1→4)-α-GlcNAc6S (1→ (7.39%) and →4)-β-GlcA-(1→4)-α-GlcNS6S (1→ (7.63%). The antithrombotic activity of M2 was evaluated using measurements of the anticoagulant effect in vitro and the fibrinolytic capability in vitro and in vivo, and M2 has 122.4 U/mg of anticoagulant activity and 1.41 U/mg of fibrinolytic activity, respectively. Additionally, a mouse tail-cutting model was used to assess the bleeding effect in real time, it found that M2 had a reduced hemorrhagic risk than heparin. Consequently, M2 could be exploited to develop functional foods or medications with antithrombotic properties.

IntroductionSargassum fusiform is considered a traditional Chinese medicinal herb to treat many diseases, Sargassum fusiform polysaccharides (SFPS) were found to display many important biological activities. The purpose of this study was to investigate the in vitro antioxidant activity of crude polysaccharide from Sargassum fusiforme and its protective effect against H2O2-induced injury in LO2 cells.MethodsSFPS was extracted from Sargassum fusiforme using water extraction and alcohol precipitation. High-performance liquid chromatography (HPLC) was used to measure its monosaccharide composition. The in vitro antioxidant activity of SFPS was evaluated using scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical assays. Moreover, its hepatoprotective activity was examined by establishing H2O2-induced LO2 cells injury model.Results and discussionThe results showed that the SFPS was composed of Glc, Ara, Fuc, Gal, Man, Rha and Xyl. Meanwhile, SFPS exhibited strong antioxidant activity and potential hepatoprotective effect. Further studies found that SFPS could alleviate LO2 cells injury induced by H2O2 via decreasing malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels, increasing superoxide dismutase (SOD) and catalase (CAT) activities and inhibiting intracellular reactive oxygen species (ROS) production. These results revealed that SFPS had the ability to protect the liver cells from H2O2-induced liver injury through its antioxidant activity.

The gut microbiota dysbiosis is a state which the physiological combinations of flora are transformed into pathological combinations caused by factors such as diets, pollution, and drugs. Increasing evidence shows that dysbiosis is closely related to many diseases. With the continuous development and utilization of marine resources, marine polysaccharides have been found to regulate dysbiosis in many studies. In this review, we introduce the types of dysbiosis and the degree of it caused by different factors. We highlight the regulating effects of marine polysaccharides on dysbiosis as a potential prebiotic. The mechanisms of marine polysaccharides to regulate dysbiosis including protection of intestinal barrier, regulatory effect on gut microbiota, alteration for related metabolites, and some other possible mechanisms were summarized. And we aim to provide some references for the high-value utilization of marine polysaccharides and new targets for the treatment of gut microbiota dysbiosis by this review.

BackgroundThyroid cancer (TC), was the fastest-rising tumor of all malignancies in the world and China, predominantly differentiated thyroid cancer (DTC). However, evidence on TC stage distribution and influencing factors of late-stage were limited in China.MethodsWe carried out a retrospective study and enrolled TC patients who were first diagnosed and hospitalized in 8 hospitals in China in 2017. Logistic regression was used to evaluate associations between influencing factors and DTC stage. We extracted eligible primary DTC records newly diagnosed in 2017 from the USA's Surveillance, Epidemiology, and End Results (SEER) database. We compared clinicopathological features and surgical treatment between our DTC records and those from the SEER database.ResultsA total of 1970 eligible patients were included, with 1861 DTC patients with known stage. Among patients ≥45 years old, males (OR = 1.76, 95%CI 1.17–2.65) and those with new rural cooperative medical scheme insurance (NCMS) (OR = 1.99, 95%CI 1.38–2.88) had higher risks of late-stage DTC (stage III-IV). Compared with SEER database, over-diagnosis is more common in China [more DTC patients with onset age< 45 years old (50.3 vs. 40.7%, P < 0.001), with early-stage (81.2 vs. 76.0%, P < 0.001), and with tumors

Background We aimed to obtain a set of health state utility scores of patients with esophageal cancer (EC) and precancerous lesions in China, and to explore the influencing factors of health‐related quality of life (HRQoL). Methods A hospital‐based multicenter cross‐sectional study was conducted. From 2013 to 2014, patients with EC or precancerous lesions were enrolled. HRQoL was assessed using a European quality of life‐5 dimension (EQ‐5D‐3L) instrument. Multivariable linear regression analysis was performed to explore the influencing factors of the EQ‐5D utility scores. Results A total of 2090 EC patients and 156 precancer patients were included in the study. The dimension of pain/discomfort had the highest rate of self‐reported problems, 60.5% in EC and 51.3% in precancer patients. The mean visual analog scale (VAS) score for EC and precancer patients were 68.4 ± 0.7 and 64.5 ± 3.1, respectively. The EQ‐5D utility scores for EC and precancer patients were estimated as 0.748 ± 0.009 and 0.852 ± 0.022, and the scores of EC at stage I, stage II, stage III, and stage IV were 0.693 ± 0.031, 0.747 ± 0.014, 0.762 ± 0.015, and 0.750 ± 0.023, respectively. According to the multivariable analyses, the factors of region, occupation, household income in 2012, health care insurance type, pathological type, type of therapy, and time points of the survey were statistically associated with the EQ‐5D utility scores of EC patients. Conclusions There were remarkable decrements of utility scores among esophageal cancer patients, compared with precancer patients. The specific utility scores of EC would support further cost‐utility analysis in populations in China.

Fucoidan has many biological functions, including anti-tumor activity. Additionally, it has been suggested that low-molecular-weight fucoidans have greater bioactivities. This study aimed to examine the degradation, purification, physicochemical characterization and in vitro antitumor activity of fucoidan from Sargassum hemiphyllum (Turner) C. Agardh. Fucoidan was isolated using DEAE-cellulose-52 (F1, F2), Vc-H2O2 degration, and Sepharose CL-6B gel (DF1, DF2) from crude Sargassum fucoidans. Physicochemical characteristics of four isolated fucoidans were examined using chemical and monosaccharide composition, average molecular weight (Mw), and FTIR. Furthermore, the anti-proliferative effects of purified fucoidans on human hepatocellular carcinoma cells (HepG2), human Burkitt Lymphoma cells (MCF-7), human uterine carcinoma cells (Hela) and human lung cancer cells (A549) were analyzed by MTT method. The apoptosis of HepG2 cells was detected by flow cytometry. Our data suggest that the contents of polysaccharide, L-fucose and sulfate of DF2 were the highest, which were 73.93%, 23.02% and 29.88%, respectively. DF1 has the smallest molecular weight (14,893 Da) followed by DF2 (21,292 Da). The four fractions are mainly composed of fucose, mannose and rhamnose, and the infrared spectra are similar, all of which contain polysaccharide and sulfate characteristic absorption peaks. The results of MTT assay showed that the four fractions had inhibitory effects on HepG2 and A549 in the range of 0.5–8 mg/mL, and the four fractions had strong cytotoxic effects on HepG2 cells. DF2 had the best inhibitory effect on HepG2 (IC50 = 2.2 mg/mL). In general, the antitumor activity of Sargassum fucoidans is related to the content of L-fucose, sulfate and molecular weight, and Sargassum fucoidan has the best inhibitory effect on HepG2 hepatocellular carcinoma cells. Furthermore, when compared to MCF-7, Hela, and A549 cells, Sargassum fucoidans had the best capacity to reduce the viability of human hepatocellular carcinoma cells (HepG2) and to induce cell apoptosis, proving itself to have a good potential in anti-liver cancer therapy.

As an acidic polysaccharide, the formation of Hyaluronic acid (HA) is typically Sodium Hyaluronate (SH) for knee repair, oral treatment, skincare and as a food additive. Nevertheless, little information is available on the anti-ageing activity of SH as a food additive. Therefore, we treated C. elegans with SH, then inferred the anti-aging activity of SH by examining the lifespan physiological indicators and senescence-associated gene expression. Compared with the control group, SH (800 μg/mL) prolonged the C. elegans’ lifespans in regular, 35 °C and H2O2 environment by 0.27-fold, 0.25-fold and 1.17-fold. Simultaneously, glutathione peroxidase (GSH-Px), antioxidant enzyme superoxide dismutase (SOD) and catalase (CAT) were increased by 8.6%, 0.36% and 167%. However, lipofuscin accumulation, reactive oxygen species (ROS) and malondialdehyde (MDA) were decreased by 36%, 47.8–65.7% and 9.5–13.1%. After SH treatment, athletic ability was improved and no impairment of reproductive capacity was seen. In addition, SH inhibited the blocking effect of age-1 and up-regulated gene levels involving daf-16, sod-3, gst-4 and skn-1. In conclusion, SH provides potential applications in anti-ageing and anti-oxidation and regulates physiological function.

Heparinoid, a type of compound that has structures similar to heparin, has been found in marine organisms such as shrimp head. This shrimp waste products were used to prepare, characterize, and evaluate the antithrombotic effect of heparinoid. Two heparinoid compounds were obtained from shrimp head, and the main fraction F1 was →4)-GlcA-(1→3)-GalNAc-(1→ with Ara, while the minor fraction F2 composed mainly of the backbone as →4)-β-D-GlcA (or IdoA)-(1→4)-β-D-GlcN (or GlcNAc)-(1→. Both F1 and F2 could extend activated partial thromboplastin time and thrombin time concentration-dependently, and F2 has stronger activity than F1 at the same concentration. The potential anticoagulant mechanism of F1 and F2 may relate to their combination with more antithrombin III, which binds to and potentiates the action of antithrombin as well as inhibiting coagulation factors Xa and IIa, preventing blood clot formation. Furthermore, heparinoid F1 and F2 were found to have high fibrinolytic capability in vitro and in vivo via activating the self-fibrinolytic system. In conclusion, heparinoids (F1 and F2) derived from shrimp head wastes could be used as candidate compounds to prevent thrombosis while posing a lower hemorrhagic risk.

Adversarial examples easily mislead vision systems based on deep neural networks (DNNs) trained with softmax cross entropy (SCE) loss. The vulnerability of DNN comes from the fact that SCE drives DNNs to fit on the training examples, whereas the resultant feature distributions between the training and adversarial examples are unfortunately misaligned. Several state-of-the-art methods start from improving the inter-class separability of training examples by modifying loss functions, where we argue that the adversarial examples are ignored, thus resulting in a limited robustness to adversarial attacks. In this paper, we exploited the inference region, which inspired us to apply margin-like inference information to SCE, resulting in a novel inference-softmax cross entropy (I-SCE) loss, which is intuitively appealing and interpretable. The inference information guarantees that it is difficult for neural networks to cross the decision boundary under an adversarial attack, and guarantees both the inter-class separability and the improved generalization to adversarial examples, which was further demonstrated and proved under the min-max framework. Extensive experiments show that the DNN models trained with the proposed I-SCE loss achieve a superior performance and robustness over the state-of-the-arts under different prevalent adversarial attacks; for example, the accuracy of I-SCE is 63% higher than SCE under the PGD50un attack on the MNIST dataset. These experiments also show that the inference region can effectively solve the misaligned distribution.

The gut bacterium Akkermansia muciniphila has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-associated fatty liver disease (MAFLD). However, its underlying mechanism involved in its well-known metabolic actions needs further evaluation. The present study explored the therapeutic effect and mechanism of A. muciniphila in intervening MAFLD by using a high-fat and high-cholesterol (HFC) diet induced obese mice model. Mice treated with A. muciniphila efficiently reversed MAFLD in the liver, such as hepatic steatosis, inflammatory, and liver injury. These therapeutic effects persisted after long-term drug withdrawal and were slightly weakened in the antibiotics-treated obese mice. A. muciniphila treatment efficiently increased mitochondrial oxidation and bile acid metabolism in the gut-liver axis, ameliorated oxidative stress-induced cell apoptosis in gut, leading to the reshaping of the gut microbiota composition. These metabolic improvements occurred with increased L-aspartate levels in the liver that transported from the gut. The administration of L-aspartate in vitro or in mice displayed the similar beneficial metabolic effects mentioned above and efficiently ameliorated MAFLD. Together, these data indicate that the anti-MAFLD activity of A. muciniphila correlated with lipid oxidation and improved gut–liver interactions through regulating the metabolism of L-aspartate. A. muciniphila could be a potential agent for clinical intervention in MAFLD.

Raspberries are rich in phytochemicals with health benefits. Our previous research has shown raspberry extracts (RE) can promote longevity in Caenorhabditis elegans. The objective of this study was to determine whether the extension of lifespan was regulated by oxidative stress, and to explore the underlying mechanisms of action. The results showed that RE could ameliorate oxidative stress, which improved antioxidant enzyme activity and enhanced resistance to paraquat. Meanwhile, treatment with RE could down-regulate the overexpression of reactive oxygen species and affect the expression of antioxidant related genes. However, administration with RE abolished the extension of the lifespan of skn-1(zu135) mutants, and promoted the migration of SKN-1 into the nucleus, which inhibited the expression of skn-1 downstream gene. In conclusion, RE could ameliorate oxidative stress in C. elegans via the SKN-1/Nrf2 pathway. This study provided the theoretical basis to explore the phytochemicals in the prevention of aging regulated by oxidative stress.

In the present study, a selenium-chondroitin sulfate (SeCS) was synthesized by the sodium selenite (Na2SeO3) and ascorbic acid (Vc) redox reaction using chondroitin sulfate derived from shark cartilage as a template, and characterized by SEM, SEM-EDS, FTIR and XRD. Meanwhile, its stability was investigated at different conditions of pH and temperatures. Besides, its antioxidant activity was further determined by the DPPH and ABTS assays. The results showed the SeCS with the smallest particle size of 131.3 ± 4.4 nm and selenium content of 33.18% was obtained under the optimal condition (CS concentration of 0.1 mg/mL, mass ratio of Na2SeO3 to Vc of 1:8, the reaction time of 3 h, and the reaction temperature of 25 °C). SEM image showed the SeCS was an individual and spherical nanostructure and its structure was evidenced by FTIR and XRD. Meanwhile, SeCS remained stable at an alkaline pH and possessed good storage stability at 4 °C for 28 days. The results on scavenging free radical levels showed that SeCS exhibited significantly higher antioxidant activity than SeNPs and CS, indicating that SeCS had a potential antioxidant effect.

Abstract Background The improvement of diagnostic and therapeutic techniques has prolonged the survival time of patients with esophageal cancer. Little is known, however, about their health‐related quality of life (HRQoL) in daily life after treatment. Methods Esophageal cancer patients who had been discharged from hospitals more than one year and healthy controls identified by screening were recruited from seven study centers covering eastern, central, and western regions of China. Patients were categorized into severe dysplasia/carcinoma in situ and stages I, II, III, and IV cancer, respectively. The EQ‐5D was employed to assess HRQoL. Multivariate regression analyses were conducted. Results A total of 1456 patients and 2179 controls were recruited. After adjusting for potential confounding factors, the likelihood of reporting problems in the five dimensions of patients was 3.8 to 23.1 times higher than controls, whilst the mean EQ‐5D utility score was 0.311 (95% CI, 0.276‐0.346) lower than controls. The mean utility scores of each patient subgroup were 0.158, 0.289, 0.303, 0.296, and 0.505 (95% CIs: 0.108‐0.208, 0.243‐0.336, 0.261‐0.346, 0.244‐0.347, and 0.437‐0.573) lower than controls, respectively. Patients had the greatest impairment in the self‐care dimension compared with controls, followed by the usual activities dimension. Therapeutic regimen, duration of illness, other chronic disease status, age, and marital status also had significant impact on different aspects of HRQoL in patients. Conclusions Esophageal cancer significantly impaired patients' HRQoL in daily life after treatment. Advanced cancer stages were associated with larger decrements on health state utility. Utility scores reported here can facilitate further cost‐utility analyses.

The colloidal gold quick test card which we developed ​was used for rapid detection of Alicyclobacillus acidoterrestris (A. acidoterrestris) in apple juice concentrate. Two antibodies against A. acidoterrestris, obtained from Sprague Dawley (SD) rats and Japan White Rabbits, were adopted to construct this quick test card. The results showed that the colloidal gold quick test card had better specificity, and was more ​rapid and convenient which deserved notice especially (the test could be completed within 5–10 min) and concorded with ELISA method (we previously report) and K medium methods (traditional classical method). This new developed colloidal gold quick test card (we named it TAB quick test card) could be more convenient for apple juice safety testing.

In large-scale arable farming, multiple sequential operations involving multiple machines must be carried out simultaneously due to restrictions of short time windows. However, the coordination and planning of multiple sequential operations is a nontrivial task for farmers, since each operation may have its own set of operational features, e.g., operating width and turning radius. Taking the two sequential operations—hoeing cultivation and seeding—as an example, the seeder has double the width of the hoeing cultivator, and the seeder must remain idle while waiting for the hoeing cultivator to finish two rows before it can commence its seeding operation. A flow-shop working mode can coordinate multiple machines in multiple operations within a field when different operations have different implement widths. To this end, an auto-steering-based collaborative operating system for fleet management (FMCOS) was developed to realize an in-field flow-shop working mode, which is often adopted by the scaled agricultural machinery cooperatives. This paper proposes the structure and composition of the FMCOS, the method of operating strip segmenting, and a new algorithm for strip state updating between successive field operations under an optimal strategy for waiting time conditioning between sequential operations. A simulation model was developed to verify the state-updating algorithm. Then, the prototype system of FMCOS was combined with auto-steering systems on tractors, and the collaborative operating system for the server was integrated. Three field experiments of one operation, two operations, and three operations were carried out to verify the functionality and performance of FMCOS. The results of the experiment showed that the FMCOS could coordinate in-field fleet operations while improving both the job quality and the efficiency of fleet management by adopting the flow-shop working mode.