The effects of kelp powder and fucoidan on the intestinal digestive capacity, immune response, and bacterial community structure composition of large yellow croakers (Larimichthys crocea).

Feed terrestrial components can induce intestinal stress in fish, affecting their overall health and growth. Recent studies suggest that seaweed products may improve fish intestinal health. In this experiment, three types of feed were prepared: a basic diet (C group), a diet with 0.2 % fucoidan (F group), and a diet with 3 % kelp powder (K group). These diets were fed to large yellow croaker (Larimichthys crocea) over an 8-week period. Each feed was randomly assigned to three seawater cages (4.0 m × 4.0 m × 5.0 m) containing 700 fish per cage. The study assessed changes in growth and intestinal health, including intestinal tissue morphology, digestive enzyme activities, expression of immune-related genes, and bacterial community structure. Results showed that incorporating seaweed products into the diet improved the growth and quality traits of large yellow croakers and significantly enhanced their intestinal digestive capacity (P < 0.05). Specifically, the 0.2 % fucoidan diet significantly increased the intestinal villus length and the activities of digestive enzymes such as trypsin, lipase, and α-amylase (P < 0.05). The 3 % kelp powder diet significantly enhanced the intestinal crypt depth and the activities of trypsin and lipase (P < 0.05). Both seaweed additives significantly enhanced intestinal health by mitigating inflammatory factors. Notably, the control group's biomarkers indicated a high presence of potential pathogenic bacteria, such as Streptococcus, Pseudomonas, Enterococcus, Herbaspirillum, Neisseria, Haemophilus, and Stenotrophomonas. After the addition of seaweed additives, these bacteria were no longer the indicator bacteria, while the abundance of beneficial bacteria like Ligilactobacillus and Lactobacillus increased. Significant reductions in the expression of inflammatory factors (e.g., il-6, tnf-α, ifn-γ in the fucoidan group and il-8 in the kelp powder group) further supported these findings. Our findings suggested that both seaweed additives helped balance intestinal microbial communities and reduce bacterial antigen load. Considering the effects, costs, manufacturing, and nutrition, adding 3 % kelp powder to the feed of large yellow croaker might be preferable. This study substantiated the beneficial effects of seaweed on the aquaculture of large yellow croaker, particularly in improving intestinal health. These findings advocated for its wider and more scientifically validated use in fish farming practices.

Effective therapy of advanced breast cancer through synergistic anticancer by paclitaxel and P-glycoprotein inhibitor.

Multi-drug resistance (MDR) in advanced breast cancer (ABC) is triggered by the high expression of P-glycoprotein (P-gp), which reduces intracellular concentration of anti-tumor drugs, in turn preventing oxidative stress damage to cytoplasmic and mitochondrial membranes. It is therefore of clinical relevance to develop P-gp-specific targeted nanocarriers for the treatment of drug resistant ABC. Herein, a drug carrier targeting CD44 and mitochondria was synthesised for the delivery of encequidar (ER, P-gp inhibitor) and paclitaxel (PTX). HT@ER/PTX nanoparticles (ER:PTX molar ratio 1:1) had excellent P-gp inhibition ability and targeted mitochondria to induce apoptosis in MCF-7/PTX cells in vitro. Furthermore, HT@ER/PTX nanocarriers showed more anti-tumor efficacy than PTX (Taxol®) in a xenograft mouse model of MCF-7/PTX cells; the tumor inhibitory rates of HT@ER/PTX nanoparticles and Taxol® were 72.64% ± 4.41% and 32.36% ± 4.09%, respectively. The survival of tumor-bearing mice administered HT@ER/PTX nanoparticles was prolonged compared to that of the mice treated with Taxol®. In addition, HT@ER/PTX not only inhibited P-gp-mediated removal of toxic lipid peroxidation byproducts resulting from anti-tumor drugs but also upregulated the expression of mitochondrial dynamics-related protein, fostering oxidative stress damage, which induced activation of the Caspase-3 apoptosis pathway. Our findings indicate that mitochondria targeted co-delivery of anti-tumor drugs and P-gp inhibitors could be a practical approach in treating multi-drug resistance in ABC.

In-flight radiometric and polarimetric calibration of the Directional Polarimetric Camera onboard the GaoFen-5 satellite over the ocean.

The Directional Polarimetric Camera (DPC) is the first Chinese multi-angle polarized Earth observation satellite sensor, which was successfully launched on 9 May 2018, onboard the GaoFen-5 satellite in the Chinese High-Resolution Earth Observation Program. The DPC's observation is one of the most important space-borne multi-spectral, multi-angular polarimetric measurements of the global Earth-atmosphere system at the present stage. Although rigorous radiometric calibration had been performed for the DPC before launch, its in-flight performance may change because of the process of launch, harsh environment of space, and aging of the sensor. Due to the absence of the onboard calibration system, vicarious calibration methods are necessary for the DPC's in-flight performance monitoring and calibration. In this paper, we adapted the Rayleigh absolute calibration method, the sun glint inter-band calibration method, and the sun glint polarization calibration method to the DPC sensor. First, the calibration errors of these three methods caused by ancillary data uncertainties (e.g., aerosol, chlorophyll concentration, absorption gases amount, and wind speed) were analyzed in detail. The error budgets show that the aerosol parameters (optical thickness and aerosol model) are some of the critical factors affecting both the radiometric and polarimetric calibration accuracies for the Rayleigh and sun glint methods. The DPC radiometric and polarimetric in-flight calibration during its commissioning phase was then implemented. The absolute coefficients of short spectral bands (443, 490, 565, and 670 nm) were calibrated by the well-characterized Rayleigh scattering signal over the ocean. Using the 565 nm band as a reference band, the Rayleigh absolute calibration was then transferred to other bands (443, 490, 670, and 865 nm) through inter-band calibration using the specular reflection of the sun over the ocean. The polarization measurements of the DPC at polarized bands (490, 670, and 865 nm) were calibrated with the polarized reflection of the sun glint over ocean. The preliminary results show that the radiometric sensitivity of the DPC changed very little after launch at the four visible bands. The absolute calibration coefficient differences from pre-flight calibration are smaller than 0.5% at the 443 and 670 nm bands, while they are within ±2% at the 490 and 565 nm bands. However, a large deviation at 865 nm band of about 9% from pre-flight calibration was indicated by the sun glint inter-band calibration. The degree of linear polarization measurement of the DPC is validated with high accuracy of about 0.02 at the 865 nm band, while the deviation at 490 and 670 nm bands are relatively larger, reaching 0.04. The DPC/GaoFen-5 shows a good in-flight performance of radiometric measurement and generally reliable polarimetric measurement after launch.

Novel Stachydrine-Leonurine Conjugate SL06 as a Potent Neuroprotective Agent for Cerebral Ischemic Stroke.

As major active ingredients of the traditional Chinese medicine motherwort, stachydrine and leonurine were found to have protective effects against cerebral ischemia. However, their bioavailability in vivo was low, and their efficacy was unsatisfactory, which limited their further application. To solve these problems, the conjugates based on the structures of stachydrine and leonurine were designed and synthesized. SL06 was found to have neuronal cell survival improvement, neuronal apoptosis restraining, activation of superoxide dismutase (SOD) activity, and inhibition of lactic dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA) in vitro. In vivo, the infarction size was significantly reduced by SL06 in the middle cerebral artery occlusion rat model. SL06 could also activate protein kinase B (AKT)/glycogen synthase kinase 3ß (GSK-3ß) activity and promoted the expression of antiapoptoticprotein Bcl-2. On the other hand, the expression of the apoptosis-associated protein cleaved caspase-3 would be inhibited as well. Thus, SL06 as the neuroprotective agent has potential for the treatment of cerebral ischemic stroke.

Design, synthesis, and biological evaluation of novel stachydrine derivatives as potent neuroprotective agents for cerebral ischemic stroke.

Stachydrine is a natural product with multiple protective biological activities, including those involved in preventing cancer, ischemia, and cardiovascular disease. However, its use has been limited by low bioavailability and unsatisfactory efficacy. To address this problem, a series of stachydrine derivatives (A1/A2/A3/A4/B1/B2/B3/B4) were designed and synthesized, and biological studies were carried out in vitro and in vivo. When compared with stachydrine, Compound B1 exhibited better neuroprotective effects in vitro, and significantly reduced infarction size in the model of the middle cerebral artery occlusion rat model. Therefore, Compound B1 was selected for further research on ischemic stroke. Graphical abstract.

Dynamic Autonomous Cross Consortium Chain Mechanism in e-Healthcare.

Safe and scalable dynamic autonomous data interaction between medical institutions can increase the number of clinical trial records, which is of great significance for improving the level of medical trial collaboration, especially for clinical decision-making with regard to rare diseases. Through a preset authorization access and consensus mechanism, consortium chain provides integrity and traceability management for medical clinical data. However, how to enable users have ownership of their own medical data and share their medical data safely and dynamically between different medical institutions remains an area of particular concern. To achieve dynamic communication between medical consortium chains, this paper proposes (i) a cross-chain communication mechanism by simplifying the heterogeneous node communication topology and (ii) the construction rules of the node identity credibility path-proof to carry out dynamic construction and verification of the path-proof for cross-chain transactions. In addition, the consensus of the cross-chain transaction is modeled as a threshold digital signature process with multiple privileged subgroups; thus, the intra-chain consortium consensus based on the verification node list is extended to the cross-chain consensus. A smart contract deployment and execution scheme based on rational node value transfer mechanism is proposed by analyzing the value transfer game between nodes. Experimental results showed that the proposed scheme can not only enable patients to share their records safely and autonomously in an authorized medical consortium chain within milliseconds but also realize dynamic adaptive interaction among heterogeneous consortium chains.

Development of M10, myricetin-3-O-ß-d-lactose sodium salt, a derivative of myricetin as a potent agent of anti-chronic colonic inflammation.

Myricetin is a natural dietary flavonoid compound with multiple activities, such as anti-oxidant, anti-inflammatory, anti-carcinogenic and anti-proliferative effects. However, myricetin exhibited substantial limitations, such as poor water-solubility, and low stability in body when it was administrated by oral. To solve these problems, we designed and synthesized a series of derivatives based on the structure of myricetin. M10 was produced by adding a hydrophilic glycosylation group and then forming a sodium salt derivative, which exhibited excellent water-solubility (>100 mg/mL), and better stability in Wistar rat plasma and liver microsomes. In vivo study, M10 exhibited higher efficacy than myricetin and mesalazine in a dextran sulfate sodium (DSS) induced mice model with ulcerative colitis. In addition, M10 also exhibited high safety (LD50 > 5 g/kg) in mice. Based on these results, M10 could be developed as a potential therapeutic agent for treatment of ulcerative colitis.