Osteoarthritis (OA) is a major joint disorder characterized by cartilage matrix degradation and inflammatory responses. Chondroitin sulfate and collagen peptides are major components of cartilage extracellular matrix and have potential relevance to OA-related inflammation. Sturgeon cartilage, a major processing by-product, is an underutilized source of these bioactive fractions. However, their extraction, characterization, and combined effects on chondrocyte inflammatory responses remain insufficiently studied. In this study, chondroitin sulfate and collagen peptides were separately extracted from sturgeon cartilage. Chondroitin sulfate fraction 1 (CS-1) was obtained by ion-exchange chromatography, whereas collagen peptide fraction 3 (CP-F3) was prepared by enzymatic hydrolysis, ultrafiltration, and gel filtration chromatography. CS-1 was predominantly chondroitin 4-sulfate, with a weight-average molecular weight of approximately 3.0 × 105 Da. CP-F3 was a low-molecular-weight collagen peptide fraction enriched in peptide-related ions below m/z 500. In an IL-1β-induced inflammatory model in SW1353 chondrocyte-like cells, combined treatment with CS-1 and CP-F3 increased proteoglycan and type II collagen retention, reduced NO, iNOS, COX-2, PGE2, and IL-6 levels, and restored the MMP-3/MMP-13/TIMP-1 balance. These effects may be associated with modulation of the TLR4/MyD88/NF-κB signaling pathway. Overall, these findings provide preliminary in vitro evidence that CS-1 and CP-F3, particularly in combination, may attenuate inflammatory and matrix-degrading responses. Further in vivo and mechanistic studies are required to clarify their relevance to cartilage protection.
Sulfated fucans from sea cucumbers are potent anticoagulants, but their structural complexity has hindered understanding of their structure-activity relationship at the oligosaccharide level. Herein, we report the preparation, structural characterization, and anticoagulant evaluation of structurally defined sulfated fuco-oligosaccharides from the sea cucumber, Acaudina leucoprocta. Crude polysaccharides were fractionated by anion-exchange chromatography to obtain a fucan sulfate fraction (WS-0). Mild acid hydrolysis of WS-0 generated an oligosaccharide mixture, which was purified by sequential Bio-Gel P-2 and anion-exchange chromatography, yielding a series of oligosaccharide fractions with degrees of polymerization (DP) ranging from 1 to 9. Their structures were elucidated using ESI-MS, MS/MS, and 800 MHz NMR spectroscopy. Two structurally defined fuco-disaccharides were obtained: α-L-Fucp2S4S-(1 → 3)-α/β-L-Fucp (dWS0-4-0.14) and a mixture of α-L-Fucp2S-(1 → 3)-α/β-L-Fucp and α-L-Fucp4S-(1 → 3)-α/β-L-Fucp (dWS0-4-0.05). Among the oligosaccharide fractions, dWS0-3-1 (DP 3-6) exhibited the strongest anticoagulant activity, prolonging APTT to 47.4 ± 4.7 s and TT to 43.2 ± 1.0 s at 400 μg/mL, while showing minimal effect on PT. Comparative analysis revealed that both chain length and sulfation pattern co-determine anticoagulant potency, with 2,4-di-O-sulfation enabling shorter chains to inhibit thrombin. This study provided the first structural map of anticoagulant fuco-oligosaccharides from A. leucoprocta, identifying minimal structural motifs for activity and offering promising leads for developing novel antithrombotic agents.
Brasenia schreberi (BS) is a perennial aquatic plant of the water lily family, of which the recognition as a functional food is on the rise. Polysaccharides from BS have been found to possess antihyperglycemic and antihyperlipidemic activities. This study aimed to partially clarify the structural and evaluate the hypoglycemic potentials of Brasenia schreberi polysaccharide (BSP). In this study, BSP was isolated from the mucilage covering the surface of Brasenia schreberi (BS). SEM and AFM results verified that BSP molecules were tightly connected and formed a ring-shaped network structure. Further structural analysis showed that BSP was an acidic heteropolysaccharide with a molecular weight of 2.47 × 104 Da. It had 1,2,3-linked α-D-Galp, 1,2-linked α-D-Manp, and 1,4-linked β-GlcA residues as the main chain, with 1,3-linked α-Galp, 1,3-linked α-Fucp, 1,3-linked α-Xylp, T-Araf, and T-Rhap as side chains. The rheological results indicated that the BSP solution was a pseudoplastic fluid and exhibited shear-thinning properties. Moreover, the gel strength and texture properties of BSP tended to be higher as the BSP and Ca2+ concentration increased. More importantly, BSP exhibited good inhibitory activity against α-amylase and α-glucosidase, indicating that it may be a good candidate for a hypoglycemic functional food.
The polysaccharides from Sepia esculenta ink are potential candidates for biomedical applications due to their functional properties. In our study, a heteropolysaccharide, SE-1, isolated from Sepia esculenta ink, had a molecular weight of 13.1 kDa and a monosaccharide composition of Man:GlcN:GlcUA:GalN:Xyl:Fuc=1.00:1.38:0.65:2.89:0.76:1.99. Through partial acid hydrolysis, methylation and one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic analyses, it is indicated that the structure of SE-1 consists of →4)-α-D-GlcpNAc-(1→, →4)-α-L-Fucp-(1→, →3)-α-D-GalpNAc-(1→, →2,6)-α-D-Manp-(1→ and →3)-β-D-GlcpUA-(1→ as the main chain and single terminal β-D-Xylp-(1→, which links to O-2 of (1→2,6)-α-Manp, as the side chain. A new aminosugar-abundant heteropolysaccharide was isolated from S. esculenta ink for the first time.
This study explored the beneficial effects of canthaxanthin (CX) on dextran sulfate sodium (DSS)-induced chronic colitis in mice and its underlying mechanisms. Oral administration of CX alleviated colitis severity, as demonstrated by reduced weight loss, diarrhea, hematochezia, colon shortening, and pathological colon injury. Improvements in intestinal permeability and inflammation were indicated by significantly decreased levels of permeability markers and pro-inflammatory cytokines. Moreover, CX mitigated mucus barrier dysfunction by enhancing goblet cell proliferation and mucin-2 secretion. CX reinforced the epithelial barrier by preserving tight junction function and preventing excessive apoptosis of colonic epithelial cells. Furthermore, CX modulated DSS-induced gut microbiota dysbiosis by reshaping the diversity and structure of both bacterial and fungal communities, increasing the abundance of beneficial microbes while reducing the prevalence of harmful microbes. To conclude, CX can effectively alleviate chronic colitis via modulating intestinal barrier function and maintaining microbiome homeostasis, providing a potential dietary therapy for UC.
This study utilized GC-MS and NMR to characterize the detailed chain structure information of polysaccharide (HM0-1) from the Agelas aff. Nemoechinata sponge, and then explored its anti-liver cancer in vitro. Results showed that the HM0-1 was a homogeneous amino-polysaccharide with a molecular weight of 929 kDa, composed of mannose (Man), N-Acetyl-glucosamine (GlcNAc), N-Acetyl-galactosamine (GalNAc), galactose (Gal) and fucose (Fuc). The main chain of HM0-1 was composed of alpha-(1 -> 2)-linked Man and alpha-(1 -> 6)-linked GlcNAc, and the side chains were alpha-Galp (1 ->, alpha-Fucp-(1 -> 3)-alpha-Galp-(1 ->, alpha-Manp-(1 ->) and a branch composed of GalNAc and Gal, which was connected to the main chain through the 3-O position of -> 2)-beta-Manp-(1 -> and -> 6)-beta-Manp-(1 ->. Additionally, HM0-1 exhibited anti-liver cancer effects by inhibiting cell proliferation, migration and invasion, and inducing cell apoptosis. We further investigated the potential mechanism of HM0-1-induced apoptosis by RNA-seq, which revealed 3679 significantly altered DEGs. GO enrichment analysis of the DEGs revealed significant enrichment of 2444 GO terms throughout the differentiation process (P < 0.05). KEGG analysis showed that the DEGs were successfully annotated as members of 347 pathways, with 42 significantly enriched KEGG pathways. In conclusion, these studies can provide valuable insights into the potential development and utilization of sponge polysaccharides as marine natural bio-active compounds.
风险指引的安全裕度不同于核电传统的安全裕度,是近十年来核电行业提出的新的安全理念.文中将阐述核电传统安全裕度和风险指引安全裕度的内涵,研究风险指引的安全裕度的计算框架和蒙特卡罗抽样方法下的风险指引的安全裕度定量化技术.鉴于蒙特卡罗抽样方法下的风险指引的安全裕度定量化方法尚需完善,文中借鉴蒙特卡罗抽样次数估算方法和基于蒙特卡罗的可靠度计算方法,提出蒙特卡罗抽样方法下的风险指引的安全裕度的不确定度计算方法以及蒙特卡罗抽样次数的估算流程.
Oxidative stress and abnormal glucose metabolism are the important physiological mechanisms in the occurrence and development of diabetes. Antioxidant peptides have been reported to attenuate diabetes complications by regulating levels of oxidative stress, but few studies have focused on peptides from marine bone collagen. In this study, we prepared the peptides with a molecular weight of less than 1 kD (HNCP) by enzymolysis and ultrafiltration derived from Harpadon nehereus bone collagen. Furthermore, the effects of HNCP on blood glucose, blood lipid, liver structure and function, oxidative stress, and glucose metabolism were studied using HE staining, kit detection, and Western blotting experiment in streptozocin-induced type 1 diabetes mice. After the 240 mg/kg HNCP treatment, the levels of blood glucose, triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in streptozotocin-induced diabetes mice decreased by 32.8%, 42.2%, and 43.2%, respectively, while the levels of serum insulin and hepatic glycogen increased by 142.0% and 96.4%, respectively. The antioxidant enzymes levels and liver function in the diabetic mice were markedly improved after HNCP intervention. In addition, the levels of nuclear factor E2-related factor 2 (Nrf2), glucokinase (GK), and phosphorylation of glycogen synthase kinase-3 (p-GSK3β) in the liver were markedly up-regulated after HNCP treatment, but the glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase1 (PEPCK1) were down-regulated. In conclusion, HNCP could attenuate oxidative stress, reduce blood glucose, and improve glycolipid metabolism in streptozocin-induced type 1 diabetes mice.
Here, six phenanthrene (the smallest arm-chair graphene nanoribbon) derivatives with dithiomethyl substitutions at different positions as the anchoring groups were synthesized. Scanning tunneling microscopy break junction technique was used to measure their single molecule conductances between gold electrodes, which showed a difference as much as 20-fold in the range of ∼10-2.82 G0 to ∼10-4.09 G0 following the trend of G2,7 > G3,6 > G2,6 > G1,7 > G1,6 > G1,8. DFT calculations agree well with this measured trend and indicate that the single molecule conductances are a combination of energy alignment, electronic coupling, and quantum effects. This significant regio- and steric effect on the single molecule conductance of phenanthrene model molecules shows the complexity in the practice of graphene nanoribbons as building blocks for future carbon-based electronics in one hand but also provides good conductance tunability on the other hand.
Abstract In this study, we carried out an amplified luminescent proximity homogeneous assay (AlphaLISA) to detect sulfonamides (SAs) antibiotic residues in plasma, milk, pork, chicken, and fish. The SAs AlphaLISA method can detect 13 SAs with half‐inhibitory concentration (IC50) 2.11–29.77 ng/ml. The detection level of those SAs was 0.3–41.12 ng/ml in matrices, which satisfied the maximum residue limit (MRL) of the European Union, United States, and China. Our recoveries are in the range of 88% to 116.8% with a coefficient of variation less than 9.3% for different spiked food samples. We observed a good correlation between the AlphaLISA and liquid chromatography–tandem mass spectrometry (LC‐MS/MS) with blood samples from injected rabbits. The established AlphaLISA method provided a no‐washing, rapid, high‐throughput screening tool for SAs in food quality control, which is suitable for small‐volume samples.
Amides are essential in the chemistry of life. Detecting the chemical bond states within amides could unravel the nature of amide stabilization and planarity, which is critical to the structure and reactivity of such molecules. Yet, so far, no work has been reported to detect or measure the bond changes at the single-molecule level within amides. Here, we show that a transition between single and double bonds between N and C atoms in an amide can be monitored in real time in a nanogap between gold electrodes via the generation of distinctive conductance features. Density functional theory simulations show that the switching between amide isomers proceeds via a proton transfer process facilitated by a water molecule bridge, and the resulting molecular junctions display bimodal conductance states with a difference as much as nine times.
A polysaccharide, CSL-0.1, was isolated from the medicinal lichen, Usnea longissima. CSL-0.1 was a neutral rhamnose-containing glucogalactomannan with a molecular weight of 7.86 × 104 Da. The polysaccharide had a core mannan structure with (1 → 6)-α-d-Manp units as the main chain and was substituted at the O-2 positions with side chains containing (1 → 2)-α-d-Manp residue, [3)-α-Glcp(1 → 4)-α-Glcp(1→] and 6-O-substituted β-d-Galf units. 2-O- and 2,3-di-O-substituted Rhap units. The effects of CSL-0.1 on intestinal immunity and antioxidant activity were evaluated. CSL-0.1 increased the spleen and thymus indices in a dose-dependent manner and conferred immunomodulation on reversing the Th1/Th2-related cytokine imbalance in cyclophosphamide (CP)-induced immunosuppressed mice. CSL-0.1 could also enhance the levels of secretory immunoglobulin A in CP-injected mice. Additionally, the antioxidant levels in the liver and intestine of the mice were increased 20%–50% after intragastric injection by CSL-0.1.
Inflammation is an important pathological feature of hyperuricemia, which in turn aggravates hyperuricemia. Astaxanthin is a carotenoid with strong antioxidant capacity and possesses many biological activities. This study was aimed to evaluate the effect of astaxanthin (ASX) on hyperuricemia and kidney inflammation in potassium oxonate (PO) and hypoxanthine (HX)-induced hyperuricemic mice. Male ICR mice were administered intragastrically with PO and HX (250 mg/kg, respectively) for 14 days. ASX was given by gavage one hour after PO and HX administration. ASX treatment significantly reversed PO and HX-induced hyperuricemia and kidney inflammation in mice as evidenced by decreased serum levels of uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), and inflammatory factors (IL-1β, IL-6, and TNF-α) and increased activities of antioxidant enzymes (CAT, SOD and GSH-Px). Furthermore, ASX administration effectively inhibited the activities of key enzymes related to UA synthesis (xanthine oxidase (XOD) and adenosine deaminase (ADA)) and modulated the protein expressions of NF-κ B p65, p-NF-κ B p65, Iκ Bα, p-Iκ Bα, NLRP3, ASC, Caspase-1, and cleavedCaspase-1 involved in inflammation pathways. Our results suggested that ASX improved hyperuricemia and kidney inflammation induced by PO and HX, probably by reducing UA synthesis and suppressing the NF-κ B and NLRP3 pathways simultaneously.
In this study, a low molecular weight peptides fraction (<3 kDa, named NJSP) was isolated and purified from the skin protein hydrolysate of Nibea japonica by ultrafiltration. The in vivo immunomodulatory effects of NJSP were investigated in cyclophosphamide (CY)-induced immunosuppressed mice. The intragastric administration of NJSP (100, 200, 400 mg/kg/d) upregulated the immune organ indexes, restored the pathological histomorphology of immune organs, and improved the body weight of CY-treated mice in a time and dose-dependent manner. NJSP treatment also remarkably promoted the proliferation of splenocyte, enhanced phagocytosis of macrophages, restored delayed-type hypersensitivity (DTH). Moreover, NJSP administration dramatically improved hemolysin, tumor necrosis factor α (TNF-α), immunoglobulin (Ig) A, IgG and IgM levels in blood serum in a dose-dependent manner. Besides, NJSP also significantly increased the activities of superoxidase dismutase (SOD) and catalase (CAT), improved the total antioxidant capacity (T-AOC), and decreased malondialdehyde (MDA) levels in blood serum. These findings confirm that NJSP can protect the immune system against oxidative damage to maintain homeostasis. Finally, NJSP can serve as a promising immunomodulator with potential application in functional food and nutraceutical industry.
The density functional theory (DFT) and time-dependent density functional theory (TDDFT) were performed to investigate the ground state and excited state hydrogen-bonding dynamics of flavonoid in hydrogen donating aqueous solution. We demonstrated that the intermolecular hydrogen bond C=O•••H-O between flavonoid and water molecules is significantly strengthened in the electronically excited-state upon photoexcitation of the hydrogen-bonded complex. The radiationless deactivation via intramolecular proton transfer in excited state (ESIPT) can be facilitated by the hydrogen bond strengthening in the excited state. At the same time, quantum yields of the excited-state deactivation via fluorescence are correspondingly decreased. The total fluorescence of flavonoid in polar protic solvents can be drastically quenched by hydrogen bonding. As a consequence, we propose a fluorescence modulation mechanism by hydrogen bonding to explain fluorescence emissions of flavonoid in hydrogen- bonding solvents and no hydrogen-bonding solvents. Given that water molecules have anomalous properties that are different from other small organic molecules that form hydrogen bonds with flavonoids, this theoretical study has reference significance for the development of in vivo probes. Hopefully, the newly proposed mechanism can inspire experimentalists to develop and synthetic non-toxic high signal-to-noise ratios without the need to wash fluorescent probes for individual targets in vivo.
This study was designed to investigate the effects and underlying mechanisms of Astaxanthin (AST) on high-fructose-induced hyperuricemia (HUA) from the perspectives of the uric acid (UA) synthesis and excretion in rat models. Following six weeks of a 10% fructose diet, the level of serum UA effectively decreased in the AST groups as compared to the model group. The enzymatic activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) were significantly inhibited, and the mRNA expression levels of XOD and ADA significantly decreased after the AST administration. These results suggested that the AST reduced UA synthesis by inhibiting the mRNA expressions and enzyme activities of XOD and ADA, thereby contributing to HUA improvement. On the hand, the relative expressions of the mRNA and protein of kidney reabsorption transport proteins (GLUT9 and URAT1) were significantly down-regulated by AST, while that of the kidney secretion proteins (OAT1, OAT3 and ABCG2) were significantly up-regulated by AST. These results indicated that the AST promoted UA excretion by regulating the urate transport proteins, and thus alleviated HUA. This study suggested that the AST could serve as an effective alternative to traditional medicinal drugs for the prevention of fructose-induced HUA.
The taxonomically challenging genus Amaranthus (Family Amaranthaceae) includes important agricultural weed species that are being spread globally as grain contaminants. We hypothesized that the ALS gene will help resolve these taxonomic challenges and identify potentially harmful resistant biotypes. We obtained 153 samples representing 26 species from three Amaranthus subgenera and included in that incorporated ITS, ALS (domains C, A and D) and ALS (domains B and E) sequences. Subgen. Albersia was well supported, but subgen. Amaranthus and subgen. Acnida were not. Amaranthus tuberculatus, A. palmeri and A. spinosus all showed different genetic structuring. Unique SNPs in ALS offered reliable diagnostics for most of the sampled Amaranthus species. Resistant ALS alleles were detected in sixteen A. tuberculatus samples (55.2%), eight A. palmeri (27.6%) and one A. arenicola (100%). These involved Ala122Asn, Pro197Ser/Thr/Ile, Trp574Leu, and Ser653Thr/Asn/Lys substitutions, with Ala122Asn, Pro197Thr/Ile and Ser653Lys being reported in Amaranthus for the first time. Moreover, different resistant mutations were present in different A. tuberculatus populations. In conclusion, the ALS gene is important for species identification, investigating population genetic diversity and understanding resistant evolution within the genus Amaranthus.
Time-of-Flight (ToF) cameras require active illumination to obtain depth information thus the power of illumination directly affects the performance of ToF cameras. Traditional ToF imaging algorithms are very sensitive to illumination and the depth accuracy degenerates rapidly with the power of it. Therefore, the design of a power efficient ToF camera always creates a painful dilemma for the illumination and the performance trade-off. In this paper, we show that despite the weak signals in many areas under extreme short exposure setting, these signals as a whole can be well utilized through a learning process which directly translates the weak and noisy ToF camera raw to depth map. This creates an opportunity to tackle the aforementioned dilemma and make a very power efficient ToF camera possible. To enable the learning, we collect a comprehensive dataset under a variety of scenes and photographic conditions by a specialized ToF camera. Experiments show that our method is able to robustly process ToF camera raw with the exposure time of one order of magnitude shorter than that used in conventional ToF cameras. In addition to evaluating our approach both quantitatively and qualitatively, we also discuss its implication to designing the next generation power efficient ToF cameras.
In the present study, peptide fractions of Cyclina sinensis hydrolysates, with molecular weight (MW) < 3 kDa and highest relative proliferation rate of murine macrophage cell line RAW 264.7, were purified by a series of chromatographic purification methods, to obtain peptide fractions with immunomodulatory activity. The amino acid sequence of the peptide was identified to be Arg-Val-Ala-Pro-Glu-Glu-His-Pro-Val-Glu-Gly-Arg-Tyr-Leu-Val (RVAPEEHPVEGRYLV) with MW of 1750.81 Da, and the novel pentadecapeptide (named SCSP) was synthesized for subsequent immunomodulatory activity experiments. Results showed the SCSP enhanced macrophage phagocytosis, increased productions of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and up-regulated the protein level of inducible nitric oxide synthase (iNOS), nuclear factor κB (NF-κB), and NOD-like receptor protein 3 (NLRP3) in RAW 264.7 cells. Furthermore, the expression of inhibitor of nuclear factor κB-α (IκB-α) was down-regulated. These findings suggest that SCSP might stimulate macrophage activities by activating the NF-κB signaling pathway and can be used as a potential immunomodulatory agent in functional food or medicine.
The aim of this study was to explore the immunomodulatory effects of the Meretrix meretrix oligopeptide (MMO, QLNWD) in cyclophosphamide (CTX)-induced immune-deficient mice. Compared to untreated, CTX-induced immune-deficient mice, the spleen and thymus indexes of mice given moderate (100 mg/kg) and high (200 mg/kg) doses of MMO were significantly higher (p < 0.05), and body weight loss was alleviated. Hematoxylin-eosin (H&E) staining revealed that MMO reduced spleen injury, thymus injury, and liver injury induced by CTX in mice. Furthermore, MMO boosted the production of immunoglobulin G (IgG) and hemolysin in the serum and promoted the proliferation and differentiation of spleen T-lymphocytes. Taken together, our findings suggest that MMO plays a vital role in protection against immunosuppression in CTX-induced immune-deficient mice and could be a potential immunomodulatory candidate for use in functional foods or immunologic adjuvants.