Selective Inhibition of PTP1B by New Anthraquinone Glycosides from Knoxia valerianoides.

Protein tyrosine phosphatase 1B (PTP1B) is highly validated as a therapeutic target for type 2 diabetes. However, active site-directed PTP1B inhibitors generally suffer from poor selectivity and bioavailability. Inspired by the identification of a unique anthraquinone-coumarin hybrid from Knoxia valerianoides exhibiting good specificity for PTP1B over the highly homologous T-cell protein tyrosine phosphatase (TCPTP), further chemical investigation of this plant species led to the isolation of nine new anthraquinone glycosides (1-9) and two known ones (10 and 11). Structures were characterized by a combination of spectroscopic analyses and chemical methods. All compounds showed PTP1B inhibitory activities with IC50 values ranging from 1.05 to 13.74 µM. Compounds 4 and 8 exhibited greater than 64-fold selectivity over TCPTP. Enzyme kinetic studies revealed that compounds 4 and 7 behaved as mixed-type inhibitors. Docking studies predicted similar binding modes of these compounds at the allosteric site positioned between helices α3 and α6.

A homologous series of α-glucans from Hemicentrotus pulcherrimus and their immunomodulatory activity.

Seven macromolecular polysaccharides (HPP-2S-HPP-8S) were purified from the gonads of sea urchin Hemicentrotus pulcherrimus. They were characterized as α-glucan homologues, sharing the same α-1,4-glucan backbone substituted at C-6 positions by glucose with HPP-1S that occurs as the major polysaccharide in H. pulcherrimus, while with higher degrees of branching, and additionally possessing minor amounts of mannose and ribose. The branching degree and amounts of non-glucose branches showed a generally increasing tendency across HPP-2S - HPP-8S. These polysaccharides exhibited significant macrophage-activating effects by augmenting the secretion of NO, TNF-α and IL-6, which probably involves the activation of NF-κB and MAPKs signaling pathways. Notably, the polysaccharides with a higher degree of branching exhibited markedly enhanced immunomodulatory capacity with a lowest effective concentration of 1.95 µg/mL. This work provides new cases of bioactive α-glucans and reveals their potential application as immunomodulating agents.

Study on pore structure and the mechanical properties of sandstone-concrete binary under freeze-thaw environment.

In China's cold region water conservancy and hydropower projects, the contact interface between the dam and the reservoir bank rock is prone to cracking under external loading and freeze-thaw action, which may lead to dam-bank failure and damage and cause engineering disasters. The NMR (Nuclear Magnetic Resonance) tests and uniaxial compression tests of concrete, sandstone, and sandstone-concrete composite after different numbers of freeze-thaw cycles were carried out to analyze the pore structure development and uniaxial compression mechanical properties of the three types of specimens under different numbers of freeze-thaw cycles. The results show that freeze-thaw cycling promotes the development of pores in sandstone and concrete, and sandstone is more sensitive to low-temperature freeze-thaw than concrete. The UCS (uniaxial compressive strength) of the sandstone-concrete binary changed in a V-shaped with the increase of the dip angle of the cemented interface, and the angle had no obvious effect on the microscopic pores. The freeze-thaw effect on the deterioration of the microscopic pore structure and mechanical properties of the sandstone-concrete binary has a similar effect pattern, in which the deterioration rate of porosity and compressive strength is faster in the early freeze-thaw period, slower in the middle period, and increases in the later period compared with the middle period, but the increase is smaller than that in the early period of freeze-thaw. In addition, the relationship between the porosity and UCS of the sandstone-concrete binary under the freeze-thaw cycle environment is a quadratic parabola.

Structure elucidation and antitumor activity of a water soluble polysaccharide from Hemicentrotus pulcherrimus.

Sea urchin nowadays serves as a delicacy around the world, and its gonads accumulate abundant polysaccharides before gametogenesis. However, the structure and bioactivity of these polysaccharides remain less well understood. Herein, a water soluble polysaccharide (HPP-1S) with a molecular weight of 2.996 × 107 Da was purified from the gonads of Hemicentrotus pulcherrimus. Chemical, spectroscopic and oligosaccharide sequencing analyses revealed that HPP-1S was a highly homogeneous polysaccharide featuring a linear backbone of 1,4-linked α-d-glucose with 1,6-α-d-glucose and 1,6-α-D-glucuronic acid side chains grafted on the backbone in an alternating pattern. In vitro, HPP-1S can arrest the cell cycle at G2/M and sub-G1 phases, and induce apoptosis in Hela cells potentially by increasing expression ratio of Bax/Bcl-2. In vivo, HPP-1S exhibited obvious antitumor efficacy in Hela xenograft-bearing nude mice with low toxicity. These findings indicated that HPP-1S might serve as a potential low toxic antitumor agent.