Purification, structural characterization, and anticoagulant activity evaluation of chondroitin sulfate from codfish (Gadus macrocephalus) bones.

Chondroitin sulfate (CCS) was purified from discarded codfish (Gadus macrocephalus) bones, and its chemical structure and anticoagulant activity were assessed. CCS was obtained via enzymatic lysis and ion-exchange column chromatography, with a yield of approximately 0.15%. High-performance gel performance chromatography revealed CCS to be a largely homogeneous polysaccharide with a relatively low molecular weight of 12.3 kDa. FT-IR spectroscopy, NMR spectroscopy, and SAX-HPLC indicated that CCS was composed of monosulfated disaccharides (ΔDi4S 73.85% and ΔDi6S 19.06%) and nonsulfated disaccharides (ΔDi0S 7.09%). In vitro anticoagulation analyses revealed that CCS was able to significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) (p < 0.05). At a CCS concentration of 5 µg/mL and 25 µg/mL, APTT and TT were approximately 1.08 and 1.12 times higher, respectively, compared to the negative control group. The results indicated that CCS might offer value as a dietary fiber supplement with the potential to prevent the incidence of coagulation-related thrombosis.

Cleaner agricultural production in drinking-water source areas for the control of non-point source pollution in China.

With continuous population growth and acceleration of urbanization in China, environmental problems in drinking-water source areas have become increasingly prominent. In some places, domestic wastewater and aquaculture sewage are directly discharged into water bodies without any treatment. Also, large amounts of domestic garbage and aquaculture waste are often randomly stacked, seriously polluting the surrounding groundwater and surface water and deteriorating the water quality. Notably, some agricultural production activities can also cause non-point source pollution, resulting from eutrophication of water bodies. In some instances, these activities can lead to nitrogen losses of 0.7%-83.9% and phosphorus losses of 0.6%-82.8%. In view of this situation, the implementation of cleaner agricultural production is of great significance for protecting the environment in drinking-water source areas and maintaining drinking-water safety. Specific practicable measures include formula fertilization through soil testing, integrated pest management, and water-saving irrigation technology. For the livestock- and poultry-breeding industry, it is necessary for large-scale farms to construct excreta discharge treatment facilities, carry out harmless treatment and resource utilization of organic wastes, establish rural biogas septic tanks, and make use of domestic-sewage and livestock-breeding wastewaters. Also, fixed garbage-dumping sites should be built in rural water-source areas, and a unified garbage-disposal station set up to reduce the pollution discharge of domestic garbage. Moreover, it is crucial to strictly control the development and utilization of hillsides in the middle and upper reaches of the drinking-water source area, as well as strengthen the restoration of vegetation and the construction of soil and water conservation forests in these areas.

Double-sided effect of tumor microenvironment on platelets targeting nanoparticles.

The cancer cells and stromal cells in tumor microenvironment secrete cytokines and recruit "homing" cells (macrophage, lymphocytes, platelets, etc.). Platelets can interact with tumor microenvironment and specifically aggregate at tumor sites. Surprising, we observed different "homing" effects of activated platelets in breast cancer model and pancreatic cancer model which is highly related with the blood supply of tumors. Besides, platelets targeting magnetic nanoparticles (MNPs) can home to breast cancer but be repelled from pancreatic cancer. We observed the targeting effect of MNPs is highly related with the expressions of collagen Ⅰ (marker of extracellular matrix) and CD34 (marker of tumor neovascularization). The homing nanoparticles such as platelets targeting MNPs could realize the tumor targeting ability, photo-thermal effect and tumor immunotherapeutic ability in the accessible tumor (e.g. breast cancer) but not the hypovascular tumor (e.g. pancreatic cancer).

A targeting theranostics nanomedicine as an alternative approach for hyperthermia perfusion.

Real-time monitoring drug-release is often regarded crucial in theranostics nanomedicine design, since it provides precise establishment of spatio-temporal activation of the drug-release in vitro and in vivo. A symmetrical self-immolative drug-dye conjugation (DDC) prodrug is developed in this study with disulfide bond as the trigger. The prodrug can be escorted by targeting PEG-PLGA micelles and hereby accumulated in the tumor by both active and passive targeting effect. Glutathione (GSH) with higher concentration in the tumor microenvironment can readily cleave the disulfide bond to initiate a subsequent decomposition of DDC, where the drug and dye can be released simultaneously in a strict one-to-one mode. Upon the disintegration, the "Turned-On" probe can emit near-infrared (NIR) fluorescence, with the aim of providing accurate and real-time information for the prodrugs' activation and biodistribution in vivo in a non-invasive way. Furthermore, the released dye can meanwhile act as a photothermic sensitizer, which can in-situ assist a deep penetration for the released drug in the tumor tissue with enhanced therapeutic efficiency. This "babysitting" strategy provides new reference for designing versatile theranostic nanomedicines for preclinical evaluations and an alternative approach for hyperthermia perfusion in clinic.