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Diffusions interacting through a random matrix: universality via stochastic Taylor expansion

Consider $$(X_{i}(t))$$ solving a system of N stochastic differential equations interacting through a random matrix $${\mathbf {J}} = (J_{ij})$$ with independent (not necessarily identically distributed) random coefficients. We show that the trajectories of averaged observables of $$(X_i(t))$$ , initialized from some $$\mu $$ independent of  $${\mathbf {J}}$$ , are universal, i.e., only depend on the choice of the distribution $$\mathbf {J}$$ through its first and second moments (assuming e.g., sub-exponential tails). We take a general combinatorial approach to proving universality for dynamical systems with random coefficients, combining a stochastic Taylor expansion with a moment matching-type argument. Concrete settings for which our results imply universality include aging in the spherical SK spin glass, and Langevin dynamics and gradient flows for symmetric and asymmetric Hopfield networks.

Probability theory and related fields SCI,SCIE | 2021 | 180 (3)

What dominates the changeable pharmacokinetics of natural sesquiterpene lactones and diterpene lactones: a review focusing on absorption and metabolism

Sesquiterpene lactones (STLs) and diterpene lactones (DTLs) are two groups of common phytochemicals with similar structures. It's frequently reported that both exhibit changeable pharmacokinetics (PK) in vivo, especially the unstable absorption and extensive metabolism. However, the recognition of their PK characteristics is still scattered. In this review, representative STLs (atractylenolides, alantolactone, costunolide, artemisinin, etc.) and DTLs (ginkgolides, andrographolide, diosbulbins, triptolide, etc.) as typical cases are discussed in detail. We show how the differences of treatment regimens and subjects alter the PK of STLs and DTLs, with emphasis on the effects from absorption and metabolism. These compounds tend to be quite permeable in intestinal epithelium, but gastrointestinal pH and efflux transporters (represented by P-glycoprotein) have great impact and result in the unstable absorption. As the only characteristic functional moiety, the metabolic behavior of lactone ring is not dominant. The α, β-unsaturated lactone moiety has the strongest metabolic activity. While with the increase of low-activity saturated lactone moieties, the metabolism is led by other groups more easily. The phase I (oxidation, reduction and hydrolysis reaction) and II metabolism (conjugation reaction) are both extensive. CYP450s, mainly CYP3A4, are largely involved in biotransformation. However, only UGTs (UGT1A3, UGT1A4, UGT2B4 and UGT2B7) has been mentioned in studies about phase II metabolic enzymes. Our work offers a beneficial reference for promoting the safety evaluation and maximizing the utilization of STLs and DTLs.

DRUG METABOLISM REVIEWS SCI,SCIE | 2021 | 53 (1)

ARPI, β-AS, and UGE regulate glycyrrhizin biosynthesis in Glycyrrhiza uralensis hairy roots

ARPI, β-AS, and UGE were cloned from G. uralensis and their regulatory effects on glycyrrhizin biosynthesis were investigated. β-AS and UGE but not ARPI positively regulate the biosynthesis of glycyrrhizin. Glycyrrhiza uralensis Fisch. has been used to treat respiratory, gastric, and liver diseases since ancient China. The most important and widely studied active component in G. uralensis is glycyrrhizin (GC). Our pervious RNA-Seq study shows that GC biosynthesis is regulated by multiple biosynthetic pathways. In this study, three target genes, ARPI, β-AS, and UGE from different pathways were selected and their regulatory effects on GC biosynthesis were investigated using G. uralensis hairy roots. Our data show that hairy roots knocking out ARPI or UGE died soon after induction, indicating that the genes are essential for the growth of G. uralensis hairy roots. Hairy roots with β-AS knocked out grew healthily. However, they failed to produce GC, suggesting that β-AS is required for triterpenoid skeleton formation. Conversely, overexpression of UGE or β-AS significantly increased the GC content, whereas overexpression of ARPI had no obvious effects on GC accumulation in G. uralensis hairy roots. Our findings demonstrate that β-AS and UGE positively regulate the biosynthesis of GC.

Plant Cell Reports SCI,SCIE | 2021 | 40 (7)

Dichotomous effects on lymphatic transport with loss of caveolae in mice

Aim Fluid and macromolecule transport from the interstitium into and through lymphatic vessels is necessary for tissue homeostasis. While lymphatic capillary structure suggests that passive, paracellular transport would be the predominant route of macromolecule entry, active caveolae-mediated transcellular transport has been identified in lymphatic endothelial cells (LECs) in vitro. Caveolae also mediate a wide array of endothelial cell processes, including nitric oxide regulation. Thus, how does the lack of caveolae impact “lymphatic function”? Methods Various aspects of lymphatic transport were measured in mice constitutively lacking caveolin-1 (“CavKO”), the protein required for caveolae formation in endothelial cells, and in mice with a LEC-specific Cav1 gene deletion (Lyve1-Cre x Cav1flox/flox; “LyCav”) and ex vivo in their vessels and cells. Results In each model, lymphatic architecture was largely unchanged. The lymphatic conductance, or initial tissue uptake, was significantly higher in both CavKO mice and LyCav mice by quantitative microlymphangiography and the permeability to 70 kDa dextran was significantly increased in monolayers of LECs isolated from CavKO mice. Conversely, transport within the lymphatic system to the sentinel node was significantly reduced in anaesthetized CavKO and LyCav mice. Isolated, cannulated collecting vessel studies identified significantly reduced phasic contractility when lymphatic endothelium lacks caveolae. Inhibition of nitric oxide synthase was able to partially restore ex vivo vessel contractility. Conclusion Macromolecule transport across lymphatics is increased with loss of caveolae, yet phasic contractility reduced, resulting in reduced overall lymphatic transport function. These studies identify lymphatic caveolar biology as a key regulator of active lymphatic transport functions.

Acta Physiologica SCI,SCIE | 2021 | 232 (4)

Hydrogel: Diversity of Structures and Applications in Food Science

Hydrogels are a series of soft and wet materials with three dimensions of crosslinked networks. Hydrogels have attracted great attention due to their diverse functional properties, and their wide range of applications, such as in soft robots and actuators, stretched electronic devices, tissue engineering materials, controlled-release drug delivery vehicles, biomedicine materials, food science, and (bio)sensors. In general, there are four core concerns in hydrogel science, including the polymer source, structure fabrication, gel function, and gel applications. According to the logic that the “structure determines function”, it is believed that rational design of structures can effectively regulate the functions and applications of hydrogels. Hence, in the current review, “structure” as the core topic will be highly regarded, and the crosslinking mechanisms and structural diversity of hydrogels are comprehensively summarized. Additionally, hydrogels also show their great application potential in food science. Hence, the current review also pays more attention to the application of hydrogels in food nutrition and health, food engineering and processing, and food safety. It is whished that this review not only serves as a reference for improving the comprehensive understanding of the structural design of hydrogels but also provides a forward-looking idea for hydrogel applications in food science.

Food Reviews International EI,SCI,SCIE | 2021 | 37 (3)