Co-assembling nanoparticles of Asiatic acid and Caffeic acid phenethyl ester: Characterization, stability and bioactivity in vitro.

Caffeic acid phenethyl ester (CAPE) is an efficient bioactive polyphenol ester derived from propolis. However, its poor water solubility, bioavailability, and stability significantly limit its application. Based on the assembly properties of some natural small molecules (NSMs), asiatic acid-caffeic acid phenethyl ester nanoparticles (ASA-CAPE NPs) were prepared to overcome the above defects. After proportion optimization, the encapsulation and loading efficiencies of ASA-CAPE NPs reached 47.72 ± 0.17 % and 11.62 ± 0.42 %, respectively. Characterization results showed that ASA-CAPE NPs, mainly assembled by hydrogen bonds and hydrophobic forces, possessed regular spherical morphology with a diameter size of less than 300 nm. Additionally, ASA-CAPE NPs presented improved water solubility, stability, and bioactivities than free CAPE. Besides, ASA-CAPE NPs also exhibited good sustained release of CAPE during the gastrointestinal digestion in vitro. Above all, ASA-CAPE NPs provide a new idea for efficiently utilizing hydrophobic active compounds in the functional food field.

Extraction optimization, purification, and biological properties of polysaccharide from Chinese yam peel.

In this study, the Chinese yam peel polysaccharide (CYPP) was obtained under the extraction conditions optimized by the Response Surface Methodology (RSM). Further biological properties of CYPP-1 purified from CYPP were also determined. The results indicated that the optimum extraction conditions were an extraction temperature of 90.5°C, a liquid-solid ratio of 28.0 ml/g, and an extraction time of 2.94 h, along with a yield of 8.81 ± 1.48%. CYPP-1 was identified as a kind of heteropolysaccharide mostly composed of glucose and galactose (59.4:1.0). The molecular weights were two main parts of 50.5 kDa (54.77%) and 4.4 kDa (21.02%), and the triple-helix conformation was not formed in CYPP-1. Besides, CYPP-1 showed good biological properties including in vitro antioxidant activity and immunomodulatory function on RAW264.7 cells, as well as favorable hypoglycemic effect. Overall, the high-value utilization of CYPP-1 reveals a broad application prospect in the industrial production of functional foods and pharmaceuticals. PRACTICAL APPLICATIONS: Yam peel, which is discarded in large quantities during postharvest processing, results in the production of tremendous by-products and is a great waste of resources. In this study, the yield of water-soluble polysaccharide from yam peel reached 8.81 ± 1.48%. Besides, the purified CYPP-1 exhibited excellent antioxidant activity, favorable immunomodulatory function, and hypoglycemic effect. The high productivity and bioactive effects are both great merits for Chinese yam peel polysaccharide as a promising candidate for foods and medicines industrial production.

Discovery of an insulin-induced gene binding compound that ameliorates nonalcoholic steatohepatitis by inhibiting sterol regulatory element-binding protein-mediated lipogenesis.

BACKGROUND AND AIMS: NASH is associated with high levels of cholesterol and triglyceride (TG) in the liver; however, there is still no approved pharmacological therapy. Synthesis of cholesterol and TG is controlled by sterol regulatory element-binding protein (SREBP), which is found to be abnormally activated in NASH patients. We aim to discover small molecules for treating NASH by inhibiting the SREBP pathway. APPROACH AND RESULTS: Here, we identify a potent SREBP inhibitor, 25-hydroxylanosterol (25-HL). 25-HL binds to insulin-induced gene (INSIG) proteins, stimulates the interaction between INSIG and SCAP, and retains them in the endoplasmic reticulum, thereby suppressing SREBP activation and inhibiting lipogenesis. In NASH mouse models, 25-HL lowers levels of cholesterol and TG in serum and the liver, enhances energy expenditure to prevent obesity, and improves insulin sensitivity. 25-HL dramatically ameliorates hepatic steatosis, inflammation, ballooning, and fibrosis through down-regulating the expression of lipogenic genes. Furthermore, 25-HL exhibits both prophylactic and therapeutic efficacies of alleviating NASH and atherosclerosis in amylin liver NASH model diet-treated Ldlr-/- mice, and reduces the formation of cholesterol crystals and associated crown-like structures of Kupffer cells. Notably, 25-HL lowers lipid contents in serum and the liver to a greater extent than lovastatin or obeticholic acid. 25-HL shows a good safety and pharmacokinetics profile. CONCLUSIONS: This study provides the proof of concept that inhibiting SREBP activation by targeting INSIG to lower lipids could be a promising strategy for treating NASH. It suggests the translational potential of 25-HL in human NASH and demonstrates the critical role of SREBP-controlled lipogenesis in the progression of NASH by pharmacological inhibition.

Cullin 4b-RING ubiquitin ligase targets IRGM1 to regulate Wnt signaling and intestinal homeostasis.

Hierarchical organization of intestine relies on the self-renewal and tightly regulated differentiation of intestinal stem cells (ISCs). Although signals like Wnt are known to sustain the continued intestinal renewal by maintaining ISCs activity and lineage commitment, molecular mechanisms underlying ISCs 'stemness' and supportive niche have not been well understood. Here, we found that CUL4B-RING ubiquitin ligase (CRL4B) regulates intestinal homeostasis by targeting immunity-related GTPase family M member 1 (IRGM1) for proteasomal degradation. CUL4B was mainly expressed at ISCs zone. Deletion of Cul4b led to reduced self-renewal of ISCs and a decreased lineage differentiation towards secretory progenitors through downregulated Wnt signals. Besides, Cul4b-null mice exhibited impaired Paneth cells number and structure. Mechanistically, CRL4B complex were associated with WD40 proteins and targeted IRGM1 at K270 for ubiquitination and proteosomal degradation. Impaired intestinal function caused by CUL4B deletion was rescued by down-regulation of its substrate IRGM1. Our results identified CUL4B as a novel regulator of ISCs and revealed a new 26 S proteasome degradation mechanism in intestine self-renewal and lineage commitment.

Non-point source pollution loads estimation in Three Gorges Reservoir Area based on improved observation experiment and export coefficient model.

The non-point source (NPS) pollution has become an important limitation to the sustainable development of the Three Gorges Reservoir Area (TGRA) water resources. NPS load estimation research has theoretical and realistic significance for water environment security and water pollution control. Therefore, the TGRA was chosen to be the study area, and the export coefficients of different land-use type were calculated through literature consultation method combined with improved observation experiment. The load of total nitrogen (TN) and total phosphorus (TP) of NPS from different pollution sources including farmland, decentralized livestock and poultry breeding and domestic pollution sources were estimated. The results are shown as follows: the order of TN load of different sources in the TGRA from high to low was land use, livestock and poultry breeding, rural life; the TN from land use was 372% higher than that of rural; the order of TP load of different sources in the TGRA from high to low was livestock and poultry breeding, rural life, land use; the TP from livestock and poultry breeding was 114.5% higher than that of land use. Therefore, control of livestock and poultry sewage discharges was the key practice to limit the TP loss, while the optimization of agricultural management was the key practice to control the loss of TN.

Development of educational modules for MRTs to better support patients with intellectual and developmental disabilities undergoing imaging procedures: A collaborative patient-oriented initiative.

BACKGROUND: Patients with intellectual and developmental disabilities (IDD) experience increased anxiety when undergoing medical imaging procedures for a variety of reasons including sensory overload, comprehension difficulty, and meeting unfamiliar people. There are several strategies that medical radiation technologists (MRTs) can apply to improve the imaging process. The purpose of this project was to work together with patients to develop educational modules and resources for MRTs on how to best support patients with IDD during medical imaging procedures. DEVELOPMENT PROCESS AND FINDINGS: The project team used a four stage process to (1) determine the educational needs of MRTs around imaging procedures for people with IDD and (2) develop a series of online case-based video modules of challenges and improved practices with accompanying digital resources. First, the project team created and distributed a needs assessment survey to MRTs to identify their educational needs, experience, and interest in learning more about how to best support patients with IDD. The results from this needs assessment underscored that developing skills to better support patients with IDD was an area of interest and need amongst OAMRS members, which led to the formation of a working group whose goal was to identify priority topics and how to best teach these topics. Second, we conducted a focus group with adults with IDD, who had experience with imaging procedures, to ensure the lived experience of people with IDD was a pillar of the modules. Third, we developed a set of video scripts and educational slides, informed by the needs assessment with MRTs and the focus group with adults with IDD. The video scripts focused on four scenarios: (1) Waiting for an imaging procedure, (2) & (3) the imaging process (MRI and PET), and (4) the exit interview. Each of these videos focused on common practice errors made during these scenarios, followed by strategies to address those errors. The educational slides focused on: (1) an introduction to people with IDD (2) Communication and (3) Triggers and Strategies. The fourth and final phase focused on filming the teaching videos with actors with IDD and finalizing the educational slides. Together, the set of educational slides and videos formed the modules for MRTs that will be published online. LESSONS LEARNED: Undertaking this process to develop educational modules for MRTs on working with people with IDD taught us that people with IDD have lived experiences which should inform the development of educational material; they must be treated as partners during this development process; and a partnered process takes time to carry out. CONCLUSION: The process that was undertaken allowed the team to develop resources, which can be used by MRTs. Evaluation of the educational modules can inform further refinement and improvement.

Factors that affect the growth and photosynthesis of the filamentous green algae, Chaetomorpha valida, in static sea cucumber aquaculture ponds with high salinity and high pH.

Chaetomorpha valida, dominant filamentous green algae, can be harmful to sea cucumber growth in aquaculture ponds of China. In order to understand the environmental factors affecting the growth of C. valida in sea cucumber aquaculture ecosystems, a combination of field investigations and laboratory experiments were conducted. Field surveys over one year revealed that C. valida survived in sea cucumber aquaculture ponds in salinities ranging from 24.3 ± 0.01‰ to 32.0 ± 0.02‰ and a pH range of 7.5 ± 0.02-8.6 ± 0.04. The high salinity and pH during the period of low C. valida biomass from January to May lay the foundation for its rapid growth in the following months of June to October. Many factors interact in the field environment, thus, laboratory experiments were conducted to determine the isolated effects of pH and salinity on C. valida growth. In laboratory experiments, samples were incubated under different salinity and pH conditions at 25 °C, with a light intensity of 108 µmol photon·m-2·s-1, and a photoperiod of 12 L:12 D. Results showed that salinity and pH significantly affect the growth and F v/F m (quantum yield of photosynthesis) of C. valida (p < 0.01). C. valida grew the longest at a salinity of 34‰ and a pH of 8.0. At 34‰ salinity, C. valida grew to 26.44 ± 5.89 cm in 16 days. At a pH of 8.0, C. valida grew to 67.96 ± 4.45 cm in 32 days. F v/F m was 0.635 ± 0.002 at a salinity of 32‰, and 0.550 ± 0.006 to 0.660± 0.001 at pH 7.0 to 8.5. Based on these results, we conclude that C. valida can bloom in sea cucumber ponds due to the high salinity and pH of coastal sea waters, which promote growth and maintain the photosynthetic activity of C. valida.

Neuroligin 3 R451C mutation alters electroencephalography spectral activity in an animal model of autism spectrum disorders.

Human studies demonstrate that sleep impairment is a concurrent comorbidity of autism spectrum disorders (ASD), but its etiology remains largely uncertain. One of the prominent theories of ASD suggests that an imbalance in synaptic excitation/inhibition may contribute to various aspects of ASD, including sleep impairments. Following the identification of Nlgn3R451C mutation in patients with ASD, its effects on synaptic transmission and social behaviours have been examined extensively in the mouse model. However, the contributory role of this mutation to sleep impairments in ASD remains unknown. In this study, we showed that Nlgn3R451C knock-in mice, an established genetic model for ASD, exhibited normal duration and distribution of sleep/wake states but significantly altered electroencephalography (EEG) power spectral profiles for wake and sleep.