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The significance of photodegradation in litter decomposition has gained recognition in arid and semi-arid terrestrial ecosystems. However, few studies have directly examined the effects of photodegradation in hyper-arid regions (annual precipitation < 150 mm) and the role of microorganisms within this process. This study investigated how two different light conditions (full sun and shade) affected the one-year decomposition process of litter from three different species in a hyper-arid region. This study analyzed the impact of varying light conditions on litter mass loss and examined changes in the soil bacterial and fungal community composition during the decomposition process. This study found that litter exposed to environmental sunlight experienced a higher rate of mass loss compared to shade-exposed litter. Full sun conditions increased mass loss by 8.34% to 21.66%. During the litter decomposition process under full sun conditions, decomposition was not influenced by differences in initial litter composition, including variations in carbon, nitrogen, lignin, and cellulose contents. However, under shade conditions, Populus euphratica leaf litter, characterized by lower nitrogen and higher cellulose and C: N ratio, exhibited significantly lower mass loss compared to Alhagi sparsifolia and Karelinia caspia, indicating a slower decomposition of low-quality litter. Full sun conditions did not significantly change the number of bacterial and fungal ASVs in the hyper-arid desert soils during the litter decomposition period. During the litter decomposition process in the hyper-arid region, the dominant bacterial phyla were Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes, while the dominant fungal phyla were Ascomycota and Basidiomycota. These results indicate that the higher mass loss under full sun was likely driven by the combined effects of photodegradation and microbial activity. Solar radiation plays a significant role in desert litter decomposition by accelerating mass loss, potentially through both direct photodegradation and indirect microbial facilitation, while microbial community structure remains resilient under high radiation.

Fucoidan, a sulfated glycan derived from brown algae, has garnered significant attention for its anticoagulant properties. However, the structural complexity and heterogeneity of naturally extracted fucoidan have hindered a comprehensive understanding of its structure-activity relationship, limiting the development of fucoidan-based anticoagulant drugs. To address this challenge, we synthesize a diverse library of 58 distinct fucoidans with multiple contiguous 1,2- cis glycosidic bonds, ranging from disaccharides to dodecasaccharides, using a highly efficient preactivation-based one-pot glycosylation strategy. This library includes compounds with various sulfation patterns (2,3- O - di- , 3,4- O - di- , and 2,3,4- O - tri -sulfation) encompassing nearly all possible fucoidan structures. In vitro anticoagulant assays demonstrate that both molecular size and degree of sulfation play crucial roles in anticoagulant potency. Notably, compounds 29 , 30 , 37 , and 58 significantly prolong human plasma activated partial thromboplastin time (APTT), comparable to the effect of enoxaparin, without affecting prothrombin time (PT) or thrombin time (TT). This selective inhibition of the intrinsic coagulation pathway suggests a reduced risk of bleeding, highlighting the therapeutic potential of these fucoidans as safer anticoagulant agents. Fucoidan is a sulfated glycan with anticoagulant properties, but its structural complexity and heterogeneity hinders understanding of its structure-activity relationship. Here, the authors synthesize a diverse library of 58 distinct fucoidans with multiple contiguous 1,2- cis glycosidic bonds and various sulfation patterns, and investigate their anticoagulant activity.

The selectin family constitutes a well-known class of immune-regulatory molecules, among which P-selectin has emerged as a therapeutic target for inflammatory thrombotic diseases due to its capacity to mediate the adhesion between multiple immune cell subsets and endothelial cells. Currently, small-molecule or glycomimetic inhibitors targeting P-selectin have stalled in Phase III clinical trials, with a common limitation being their weak binding affinity to P-selectin. In this study, in vitro competitive binding assays were employed to evaluate the inhibitory effects of structurally distinct fucosylated glycosaminoglycan (FG) oligosaccharides, derived from sea cucumbers, on the interaction between P-selectin and its ligands. A potent inhibitor, the nonasaccharide Ta-9-2 (featuring a novel disaccharide side chain), was identified. Biolayer interferometry (BLI) analysis further confirmed its high binding affinity to P-selectin, with a KD of 83.92 nM. Structure–activity relationship (SAR) analysis reveals that the appropriate glycan chain length, the novel disaccharide side chain (Gal4S6S-α1,2-L-Fuc3S-α1,3), and the favorable sulfation pattern (Fuc2S4S) serve as the molecular basis for potent P-selectin inhibition. This study provides a robust theoretical foundation for the structural optimization of glycomimetic targeting P-selectin, while also offering a new opportunity for the development of high-efficacy drug candidates.

Sulfated polysaccharides from sea cucumbers possess distinct chemical structure and various biological activities. Herein, three types of polysaccharides were isolated and purified from Pattalus mollis, and their structures and bioactivities were analyzed. The fucosylated glycosaminoglycan (PmFG) had a CS-like backbone composed of the repeating units of -4-d-GlcA-β-1,3-d-GalNAc4S6S-β-1-, and branches of a sulfated α-l-Fuc (including Fuc2S4S, Fuc3S4S and Fuc4S with a molar ratio of 2:2.5:1) linked to O-3 of each d-GlcA. The fucan sulfate (PmFS) had a backbone consisting of a repetitively linked unit -4-l-Fuc2S-α-1-, and interestingly, every trisaccharide unit in its backbone was branched with a sulfated α-l-Fuc (Fuc4S or Fuc3S with a molar ratio of 4:1). Apart from the sulfated polysaccharides, two neutral glycans (PmNG-1 & -2) differing in molecular weight were also obtained and their structures were similar to animal glycogen. Anticoagulant assays indicated that PmFG and PmFS possessed strong APTT prolonging and intrinsic factor Xase inhibition activities, and the sulfated α-l-Fuc branches might contribute to the anticoagulant and anti-FXase activities of both PmFG and PmFS.

The plasma contact system sits atop the intrinsic coagulation cascade and plasma kallikrein–kinin pathway, and in vivo its activation contributes, respectively, to coagulation and inflammation mainly via two downstream pathways. This system has been widely investigated, its activation mechanisms by negatively charged surfaces and the interactions within its components, factor XII, prekallikrein and high molecular weight kininogen are well understood at the biochemical level. However, as most of the activators that have been discovered by in vitro experiments are exogenous, the physiological activators and roles of the contact system have remained unclear and controversial. In the last two decades, several physiological activators have been identified, and a better understanding of its roles and its connection with other signaling pathways has been obtained from in vivo studies. In this article, we present an overview of the contact pathway with a focus on the activation mechanisms, natural stimuli, possible physiological roles, potential risks of its excessive activation, remaining questions and future prospects.

Background Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels may help guide early prevention and treatment efforts for dyslipidemia. Methods We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw ( n  = 2,531) and in participants who did not take lipid-lowering medication ( n  = 1,869). Using interaction models, we also examined whether demographic factors including age, sex, and educational attainment modified the relationships between epigenetic age acceleration and blood lipids. Results After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG ( p  < 0.05), although the effect sizes were relatively small (e.g., < 7 mg/dL of TC per standard deviation in epigenetic age acceleration). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjustment for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment. Conclusion Multiple measures of epigenetic age acceleration are associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or non-linear relationships between age and these lipids, as both TC and LDL-C decrease faster at older ages.

Introduction: Ultraviolet (UV) radiation is believed to play a significant role in accelerating litter decomposition in water-limited ecosystems. Litter traits also influence the decomposition. However, the dominance of litter traits and ultraviolet radiation on litter decomposition in hyper-arid deserts (annual precipitation: potential evaporation < 0.05) with diverse species and seasonal variations remain unclear. Methods: To address this knowledge gap, we examined the decomposition of three dominant litter species ( Karelinia caspia , Alhagi sparsifolia , and Populus euphratica ) in the southern edge of the Taklimakan Desert, Northwest China. Results: Our results revealed that under UV radiation conditions, K. caspia , A. sparsifolia , and P. euphratica experienced mass losses of 45.4%, 39.8%, and 34.9%, respectively, and 20%, 22.2% and 17.4%, respectively under UV filtering treatment. Specifically, the loss rate of carbon and lignin under UV radiation, was 2.5 and 2.2 times higher than under UV filtering treatment, respectively. Conclusion: UV radiation did not dominate decomposition throughout the year in our study area, and the loss rate of litter traits was significantly higher in summer than in winter under UV radiation. Moreover, this photodegradation is related to the intensity of UV exposure, but not to precipitation or temperature. Surprisingly, species type had no significant effect on litter decomposition. However, when we applied a UV filtering treatment, we observed higher loss rates of nitrogen compared with the ambient treatment, suggesting the involvement of other spectra in the litter decomposition process. Overall, our findings elucidate that UV radiation is a crucial factor that affects litter mass loss. The magnitude of this effect mostly varies with the season rather than the species of litter.

dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber Holothuria fuscopunctata. As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration (Tmax) was at about 1 h, and the peak concentration (Cmax) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(T1/2β) was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies.

Fucosylated glycosaminoglycan (FG) from sea cucumber is a potent anticoagulant by inhibiting intrinsic coagulation tenase (iXase). However, high-molecular-weight FGs can activate platelets and plasma contact system, and induce hypotension in rats, which limits its application. Herein, we found that FG from T. ananas (TaFG) and FG from H. fuscopunctata (HfFG) at 4.0 mg/kg (i.v.) could cause significant cardiovascular and respiratory dysfunction in rats, even lethality, while their depolymerized products had no obvious side effects. After injection, native FG increased rat plasma kallikrein activity and levels of the vasoactive peptide bradykinin (BK), consistent with their contact activation activity, which was assumed to be the cause of hypotension in rats. However, the hemodynamic effects of native FG cannot be prevented by the BK receptor antagonist. Further study showed that native FG induced in vivo procoagulation, thrombocytopenia, and pulmonary embolism. Additionally, its lethal effect could be prevented by anticoagulant combined with antiplatelet drugs. In summary, the acute toxicity of native FG is mainly ascribed to pulmonary microvessel embolism due to platelet aggregation and contact activation-mediated coagulation, while depolymerized FG is a safe anticoagulant candidate by selectively targeting iXase.

Thrombosis underlies many life-threatening cardio-cerebrovascular diseases. Although existing anticoagulants are effective in treating thrombotic diseases, their application is limited due to the concern of bleeding. New anticoagulants that preserve hemostasis have significant clinical importance. Herein, a novel galactosylated glycosaminoglycan, with unique sequence and sulfate substitutions, was isolated from the snail Camaena cicatricose (CCG). Administration of CCG effectively inhibited thrombus formation in a rat venous thrombosis model, which is positively correlated with its ex vivo anticoagulant activity (APTT prolongation), with much lower bleeding risk compared with heparins. It is also effective in preventing thrombosis in the rat arterial-venous shunt model and endotoxin-treated mice. CCG inhibited coagulation by selectively targeting iFXase enzyme complex (FIXa–FVIIIa), in an antithrombin (AT)-independent manner. CCG can bind to FIXa with high affinity and decrease the affinity of FIXa–FVIIIa, with no effect on the FIXa activity. Compared with heparins, it cannot bind to AT and exhibits high selectivity for iFXase inhibition, consistent with its absence of the specific heparin pentasaccharide sequence. Overall, the snail galactosed glycosaminoglycan inhibits thrombosis without affecting hemostasis via disrupting iFXase (FIXa–FVIIIa). CCG may represent a promising candidate for thrombosis treatment without increased bleeding risk.