Preparation of Lutein Nanoparticles by Glycosylation of Saccharides and Casein for Protecting Retinal Pigment Epithelial Cells.

Age-related macular degeneration (AMD), a leading cause of visual impairment in the aging population, lacks effective treatment options due to a limited understanding of its pathogenesis. Lutein, with its strong antioxidant properties and ability to mitigate AMD by absorbing ultraviolet (UV) rays, faces challenges related to its stability and bioavailability in functional foods. In this study, we aimed to develop delivery systems using protein-saccharide conjugates to enhance lutein delivery and protect adult retinal pigment epithelial (ARPE-19) cells against sodium iodate (NaIO3)-induced damage. Various saccharides, including mannose, galactose, lactose, maltose, dextran, and maltodextrin, were conjugated to casein via the Maillard reaction for lutein delivery. The resulting lutein-loaded nanoparticles exhibited small size and spherical characteristics and demonstrated improved thermal stability and antioxidant capacity compared to free lutein. Notably, these nanoparticles were found to be nontoxic, as evidenced by reduced levels of cellular reactive oxygen species production (167.50 ± 3.81, 119.57 ± 3.45, 195.15 ± 1.41, 183.96 ± 3.11, 254.21 ± 3.97, 283.56 ± 7.27%) and inhibition of the mitochondrial membrane potential decrease (58.60 ± 0.29, 65.05 ± 2.91, 38.88 ± 1.81, 42.95 ± 1.39, 23.52 ± 1.04, 25.24 ± 0.08%) caused by NaIO3, providing protection against cellular damage and death. Collectively, our findings suggest that lutein-loaded nanoparticles synthesized via the Maillard reaction hold promise for enhanced solubility, oral bioavailability, and biological efficacy in the treatment of AMD.

Microfluidic fabrication of core-shell fucoxanthin nanofibers with improved environmental stability for reducing lipid accumulation in vitro.

Fucoxanthin is a xanthophyll carotenoid that possesses potent antioxidant, anti-obesity, and anti-tumor properties. However, its limited solubility in water and susceptibility to degradation create challenges for its application. In this study, a microfluidic coaxial electrospinning technique was used to produce core-shell zein-gelatin nanofibers for encapsulating fucoxanthin, enhancing its bioavailability, and improving its stability. In comparison to uniaxially-loaded fucoxanthin nanofibers, the encapsulation efficiency of fucoxanthin reached 98.58 % at a core-shell flow rate ratio of 0.26:1, representing a 14.29 % improvement. The photostability of the nanofibers increased by 74.59 % after three days, UV stability increased by 38.82 % after 2 h, and temperature stability also significantly improved, demonstrating a protective effect under harsh environmental conditions (P < 0.05). Additionally, nanofibers effectively alleviated oleic acid-induced reactive oxygen species production and reduced fluorescence intensity by 54.76 %. MTT experiments indicated great biocompatibility of the nanofibers, effectively mitigating mitochondrial membrane potential polarization and lipid accumulation in HepG2 cells. Overall, the microfluidic coaxial electrospinning technique enables promising applications of fucoxanthin delivery in the food industry.

Two Antimicrobial Peptides Derived from Bacillus and Their Properties.

Growth promotion and disease prevention are important strategies in the modern husbandry industry, and for this reason, antibiotics are widely used as animal feed additives. However, the overuse of antibiotics has led to the serious problem of increasing resistance of pathogenic microorganisms, posing a major threat to the environment and human health. "Limiting antibiotics" and "Banning antibiotics" have become the inevitable trends in the development of the livestock feed industry, so the search for alternative antimicrobial agents has become a top priority. Antimicrobial peptides (AMPs) produced by Bacillus spp. have emerged as a promising alternative to antibiotics, due to their broad-spectrum antimicrobial activity against resistant pathogens. In this study, two strains of Bacillus velezensis 9-1 and B. inaquosorum 76-1 with good antibacterial activity were isolated from commercial feed additives, and the antimicrobial peptides produced by them were purified by ammonium sulfate precipitation, anion exchange chromatography, gel chromatography, and RP-HPLC. Finally, two small molecule peptides, named peptide-I and peptide-II, were obtained from strain 9-1 and 76-1, respectively. The molecular weight and sequences of the peptides were analyzed and identified by LC-MS/MS, which were 988.5706 Da and VFLENVLR, and 1286.6255 Da and FSGSGSGTAFTLR, respectively. The results of an antibacterial activity and stability study showed that the two peptides had good antibacterial activity against Staphylococcus aureus, B. cereus, and Salmonella enterica, and the minimum inhibitory concentrations were 64 µg/mL and 16 µg/mL, 32 µg/mL and 64 µg/mL, and 8 µg/mL and 8 µg/mL, respectively. All of them have good heat, acid, and alkali resistance and protease stability, and can be further developed as feed antibiotic substitutes.

Development and validation of a nomogram model for central venous access device-related thrombosis in hospitalized children.

This study aimed to develop and validate a nomogram model of central venous access device-related thrombosis (CRT) for hospitalized children. A total of 503 consecutive cases from a hospital in Changsha City, Hunan Province were stochastically classified into the training set and internal validation set at a ratio of 7:3, and 85 consecutive cases in two hospitals in Urumqi City, Xinjiang Uygur Autonomous Region were collected as an external validation set. Univariate analysis and multivariate analysis on CRT-related risk factors of hospitalized children were conducted, a logistic regression model was employed to establish the nomogram, and the discrimination, calibration, and decision curve analysis was performed to assess the proposed nomogram model. The nomogram model involved seven independent risk factors, including blind catheterization, abnormal liver function, central line-associated bloodstream infection, infection, number of catheter lines, leukemia, and bed rest > 72 h. The discrimination results showed that the area under the receiver operating characteristic curve of the training set, internal validation set, and external validation set was 0.74, 0.71, and 0.76 respectively, and the accuracy rates of the proposed nomogram model were 79%, 72%, and 71% in the training set, internal validation set, and external validation set. The calibration results also showed that the calibration curve had great fitness for each dataset. More importantly, the decision curve suggested that the proposed nomogram model had a prominent clinical significance. CONCLUSION: The nomogram model can be used as a risk assessment tool to reduce the missed diagnosis rate and the incidence of CRT in hospitalized children. WHAT IS KNOWN: • Central venous access device-related thrombosis is generally asymptomatic for hospitalized children, causing the missed diagnosis of central venous access device-related thrombosis easily. • No risk prediction nomogram model for central venous access device-related thrombosis in hospitalized children has been established. WHAT IS NEW: • A visual and personalized nomogram model was built by seven accessible variables (blind catheterization, abnormal liver function, central line-associated bloodstream infection, infection, number of catheter lines, leukemia, and bed rest > 72 h). • The model can effectively predict the risk of central venous access device-related thrombosis for hospitalized children.

Longitudinal relationship between body mass index and depressive symptoms among Chinese adults: The moderating roles of lifestyle factors and age.

OBJECTIVE: This study aims to verify the moderating roles of lifestyle factors and age between body mass index (BMI), BMI trajectory and depressive symptoms of Chinese adults through a prospective design. METHODS: The participants who are 18 years old and above from the China Family Panel Studies (CFPS) were included in the 2016 baseline and 2018 follow-up research. BMI was calculated according to self-report weight (kilogram) and height (centimeter). Depressive symptoms were evaluated via the Center for Epidemiologic Studies Depression (CESD-20) scale. Inverse probability-of-censoring weighted estimation (IPCW) was used to check whether selection bias existed. Modified Poisson regression was performed to calculate prevalence and risk ratios as well as 95% confidence intervals. RESULTS: After adjustment, it was found that the positive associations of persistent underweight (RR = 1.154, P < 0.001) and normal weight → underweight (RR = 1.143, P < 0.001) with 2018 depressive symptoms were significant among middle-aged people, while the negative association of persistent overweight/obesity (RR = 0.972, P < 0.001) was significant in young adults. Notably, smoking moderated the relationship between baseline BMI and subsequent depressive symptoms (interaction P = 0.028). Also, exercise regularly and exercise duration weekly moderated the relationships of baseline BMI (interaction P = 0.004 and 0.015) and trajectories of BMI (interaction P = 0.008 and 0.011) with depressive symptoms among Chinese adults, respectively. CONCLUSION: Weight management strategies for underweight and normal weight → underweight adults should pay attention to the role of exercise in maintaining normal weight and improving depressive symptoms.

Predictors of Psychological Distress among Patients with Colorectal Cancer-Related Enterostomy: A Cross-sectional Study.

OBJECTIVE: To identify variables that may predict psychological distress in patients with an enterostomy. METHODS: Investigators recruited 77 patients with a stoma from a stoma clinic according to the inclusion criteria. Patients' psychological distress was assessed with the Distress Thermometer (DT) tool, and their personality type was determined by the Eysenck Personality Questionnaire. Researchers also collected demographic and disease-related data. Predictive values were estimated using multiple regression analyses. RESULTS: The mean DT score of all patients was 5.94 (SD, 1.81), and approximately 85.7% consistently suffered from psychological distress. Being unmarried and having peristomal complications were associated with higher psychological distress, whereas having a monthly income 5,000 ¥ or more was associated with lower levels of distress. Moreover, patients with a melancholic personality type tended to have higher DT scores, which could act as a strong independent predictor for psychological distress. CONCLUSIONS: The majority of patients with a stoma endured moderate to severe psychological distress during follow-up care. Exploring the related factors that predict the levels of psychological distress could enable clinicians to identify at-risk patients as early as possible and thus provide optimal care for improving patients' quality of life.

Effects of Concentration of Soybean Protein Isolate and Maltose and Oil Phase Volume Fraction on Freeze-Thaw Stability of Pickering Emulsion.

There is growing interest in enhancing the freeze-thaw stability of a Pickering emulsion to obtain a better taste in the frozen food field. A Pickering emulsion was prepared using a two-step homogenization method with soybean protein and maltose as raw materials. The outcomes showed that the freeze-thaw stability of the Pickering emulsion increased when prepared with an increase in soybean protein isolate (SPI) and maltose concentration. After three freeze-thaw treatments at 35 mg/mL, the Turbiscan Stability Index (TSI) value of the emulsion was the lowest. At this concentration, the surface hydrophobicity (H0) of the composite particles was 33.6 and the interfacial tension was 44.34 mN/m. Furthermore, the rheological nature of the emulsions proved that the apparent viscosity and viscoelasticity of Pickering emulsions grew with a growing oil phase volume fraction and concentration. The maximum value was reached in the case of the oil phase volume fraction of 50% at a concentration of 35 mg/mL, the apparent viscosity was 18 Pa·s, the storage modulus of the emulsion was 575 Pa, and the loss modulus was 152 Pa. This research is significant for the production of freeze-thaw resistant products, and improvement of protein-stabilized emulsion products with high freeze-thaw stability.

Transcriptome analysis of genes related to glucoraphanin and sulforaphane synthesis in methyl jasmonate treated broccoli (Brassica oleracea var. italica) hairy roots.

Hairy roots obtained by infecting broccoli (Brassica oleracea var. italica) leaves with Agrobacterium rhizogenes (ATCC15834) have the characteristics of phytohormone autonomy, genetic stability and can produce a large amount of the anti-cancer substance Sulforaphane (SF) and the biosynthetic precursor Glucoraphanin (GRA). Under the induction of the exogenous signaling molecule methyl jasmonate (MeJA), the production of SF in broccoli hairy roots was significantly increased. However, the molecular mechanism of GRA and SF synthesis in hairy roots of broccoli treated with MeJA has not been reported. In this study, according to the yield of GRA and SF, the best concentration of MeJA treatment for hairy roots of broccoli was selected. After 18 days of growth, broccoli hairy roots were treated with 10 mmol L-1 MeJA for 0, 3, 6, 9 and 12 h. Compared with 0 h, the yield of GRA and SF increased under other treatments. The highest yield of GRA and SF occurred at 9 h, which were 2.22-fold and 1.74-fold higher than those at 0 h. Brassica oleracea var. botrytis was used as reference genome, and 5,757 differentially expressed genes (DEG) were observed at 0, 3, 6, 9 and 12 h under 10 mmol L-1 MeJA treatment, of which 4,673 were down-regulated and 1084 were up-regulated. The key genes regulating GRA synthesis, CYP79F1, CYP83A1, UGT74B1, FMOGS-OX5 and GSL-OH, were up-regulated at 0 and 3 h, and down-regulated the rest of the time; BCAT2 was up-regulated at 6, 9, 12 h, and at 0, 3 h expression was down-regulated, transcription factors MYB28 and MYB29 were down-regulated by exogenous MeJA treatment. A pathway of GRA biosynthesis and transformation pathways in MeJA-treated broccoli hairy roots was simulated and the molecular mechanism of GRA biosynthesis and SF accumulation in broccoli hairy roots under MeJA treatment was revealed.

Neuromuscular junction disorders: Experimental models and pathophysiological mechanisms.

Located between skeletal muscle fibers and motoneurons, the neuromuscular junction is a chemical synapse essential for the transmission of information from nervous system to skeletal muscle. There are many diseases related to neuromuscular junction dysfunction, including myasthenia gravis, Lambert­Eaton myasthenic syndrome, congenital myasthenic syndromes, amyotrophic lateral sclerosis, and spinal muscular atrophy. The pathophysiological mechanisms of these diseases have been investigated using many animal models. Among them, mouse models are the most commonly used and have provided the majority of current data. Moreover, advances in human induced pluripotent stem cell technology has resulted in new opportunities to study neuromuscular junction disorders from both patients and healthy individuals. Currently, patient­specific induced pluripotent stem cells derived from motor neurons have begun to be studied. These studies will help us achieve a more comprehensive understanding of diseases related to neuromuscular junction disorders. We will describe the research models of neuromuscular junction disorders and provide an overview of recent key findings.

Transcriptomics analysis of genes induced by melatonin related to glucosinolates synthesis in broccoli hairy roots.

Glucoraphanin (GRA) is found in the seeds and vegetative organs of broccoli (Brassica oleracea L. var. italica Planch) as the precursor of anti-carcinogen sulforaphane (SF). The yield of GRA obtained from these materials is weak and the cost is high. In recent years, the production of plant secondary metabolites by large-scale hairy roots culture in vitro has succeeded in some species. Melatonin (MT) is a natural hormone which existed in numerous organisms. Studies have demonstrated that MT can improve the synthesis of secondary metabolites in plants. At present, it has not been reported that MT regulates the biosynthesis of glucoraphanin in broccoli hairy roots. In this study, the broccoli hairy roots that grew for 20 d were respectively treated by 500 µM MT for 0, 6, 12, 20 and 32. To explore the reason of changes in secondary metabolites and reveal the biosynthetic pathway of glucoraphanin at transcriptional level. Compared with 0 h, the yield of GRA under other treatments was increased, and the overall trend was firstly increased and then decreased. The total yield of GRA reached the highest at 12 h, which was 1.22-fold of 0 h. Then, the genome of broccoli as the reference, a total of 13234 differentially expressed genes (DEGs) were identified in broccoli hairy roots under treatment with 500 µM MT for 0, 6, 12, 20 and 32 h, respectively. Among these DEGs, 6266 (47.35%) were upregulated and 6968 (52.65%) were downregulated. It was found that the pathway of 'Glucosinolates biosynthesis (ko00966)' was enriched in the 16th place by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the upregulated DEGs. The expression of key genes in the GRA biosynthesis pathway was upregulated at all time points, and a deduced GRA biosynthesis pathway map was constructed for reference.

Nanoliposomes for encapsulation and calcium delivery of egg white peptide-calcium complex.

Nanoliposomes and crude liposomes loaded with egg white peptide-calcium complex (EWP-Ca) were fabricated by thin-film dispersion with or without dynamic high-pressure microfluidization. Their physiochemical properties, in vitro stability, and calcium release profiles were investigated in this study. Results showed that the EWP-Ca-loaded nanoliposomes exhibited spherical structures with a lower particle size and polydispersity index as well as a higher thermal stability as compared to the corresponding crude liposomes. Further investigations revealed that EWP-Ca was embedded into the liposomes mainly through hydrogen bonding and present in an amorphous form within the liposomes. Additionally, the EWP-Ca-loaded nanoliposomes effectively slowed the release of calcium in gastric digestion, allowing more soluble calcium to enter the intestinal tract; in the subsequent intestinal digestion, the EWP-Ca-loaded nanoliposomes were more electrically and physically stable than the crude liposomes. Therefore, the EWP-Ca-loaded nanoliposomes could be used as a favorable dietary calcium delivery system to promote calcium bioavailability. PRACTICAL APPLICATION: Nanoliposomes were fabricated in this study to encapsulate the egg white peptide-calcium complex (EWP-Ca) for calcium delivery. The EWP-Ca-loaded nanoliposomes effectively slowed the release of calcium in gastric digestion, allowing more soluble calcium to enter the intestinal tract, and were more electrically and physically stable in the subsequent intestinal digestion. Therefore, the EWP-Ca-loaded nanoliposomes may be incorporated in calcium-fortified food to enhance calcium delivery for maintaining bone health.

Effects of brewers' spent grain protein hydrolysates on gas production, ruminal fermentation characteristics, microbial protein synthesis and microbial community in an artificial rumen fed a high grain diet.

BACKGROUND: Brewers' spent grain (BSG) typically contains 20% - 29% crude protein (CP) with high concentrations of glutamine, proline and hydrophobic and non-polar amino acid, making it an ideal material for producing value-added products like bioactive peptides which have antioxidant properties. For this study, protein was extracted from BSG, hydrolyzed with 1% alcalase and flavourzyme, with the generated protein hydrolysates (AlcH and FlaH) showing antioxidant activities. This study evaluated the effects of AlcH and FlaH on gas production, ruminal fermentation characteristics, nutrient disappearance, microbial protein synthesis and microbial community using an artificial rumen system (RUSITEC) fed a high-grain diet. RESULTS: As compared to the control of grain only, supplementation of FlaH decreased (P < 0.01) disappearances of dry matter (DM), organic matter (OM), CP and starch, without affecting fibre disappearances; while AlcH had no effect on nutrient disappearance. Neither AlcH nor FlaH affected gas production or VFA profiles, however they increased (P < 0.01) NH3-N and decreased (P < 0.01) H2 production. Supplementation of FlaH decreased (P < 0.01) the percentage of CH4 in total gas and dissolved-CH4 (dCH4) in dissolved gas. Addition of monensin reduced (P < 0.01) disappearance of nutrients, improved fermentation efficiency and reduced CH4 and H2 emissions. Total microbial nitrogen production was decreased (P < 0.05) but the proportion of feed particle associated (FPA) bacteria was increased with FlaH and monensin supplementation. Numbers of OTUs and Shannon diversity indices of FPA microbial community were unaffected by AlcH and FlaH; whereas both indices were reduced (P < 0.05) by monensin. Taxonomic analysis revealed no effect of AlcH and FlaH on the relative abundance (RA) of bacteria at phylum level, whereas monensin reduced (P < 0.05) the RA of Firmicutes and Bacteroidetes and enhanced Proteobacteria. Supplementation of FlaH enhanced (P < 0.05) the RA of genus Prevotella, reduced Selenomonas, Shuttleworthia, Bifidobacterium and Dialister as compared to control; monensin reduced (P < 0.05) RA of genus Prevotella but enhaced Succinivibrio. CONCLUSIONS: The supplementation of FlaH in high-grain diets may potentially protect CP and starch from ruminal degradation, without adversely affecting fibre degradation and VFA profiles. It also showed promising effects on reducing CH4 production by suppressing H2 production. Protein enzymatic hydrolysates from BSG using flavourzyme showed potential application to high value-added bio-products.

Association between lifestyle factors and depressive symptoms among Chinese middle school students: a cross-sectional study.

This study aimed to identify the independent contributions of lifestyle factors to depressive symptoms among Chinese middle school students, with a focus on gender differences. A cross-sectional study of 3081 middle school students was conducted in Ganzhou City, Jiangxi Province, China. Students were asked to complete a questionnaire including socio-demographics, lifestyle factors, the Pittsburgh Sleep Quality Index and the Chinese Secondary School Students Depression Scale. The total prevalence of depressive symptoms was 19.9%. Poor quality of sleep, smoking, drinking and longer mobile phone use time were related to increased prevalence of depressive symptoms after adjusting for potential confounders. A significant interaction between gender and quality of sleep on the depressive symptoms was found (P = 0.014). The gender-stratified analysis showed that quality of sleep was significantly associated with depressive symptoms in both genders. However, the effect in males was greater than that in females.

Factors influencing breast cancer awareness: a cross-sectional study in China.

Aim: This study aimed to explore the factors that influence breast cancer awareness. Materials & methods: A community-based cross-sectional study was conducted between January and April 2019 in Changchun, Jilin Province, China. Results: A total of 274 women were recruited for this cross-sectional study. Participants had a moderate level of breast cancer awareness (median = 76.50 [68.75, 84.00]). Women in the action/maintenance stages reported higher breast cancer awareness (p = 0.044). Women's breast cancer awareness was positively associated with high health information literacy level, husbands' higher educational degrees, seeing doctors after detecting abnormal breast changes and living within a short distance from the nearest hospital. Conclusion: History of screening and higher health information literacy levels are important positive factors linked to higher breast cancer awareness.

Preparation of a new combination nanoemulsion-encapsulated MAGE1-MAGE3-MAGEn/HSP70 vaccine and study of its immunotherapeutic effect.

BACKGROUND: MAGE family genes have been studied as targets for tumor immunotherapy for a long time. Here, we combined MAGE1-, MAGE3- and MAGEn-derived peptides as a cancer vaccine and tested whether a new combination nanoemulsion-encapsulated vaccine could be used to inhibit the growth of tumor cells in humanized SCID mice. METHODS: The nanoemulsion-encapsulated complex protein vaccine (MAGE1, MAGE3, and MAGEn/HSP70 fusion protein; M1M3MnH) was prepared using a magnetic ultrasonic technique. After screening, human PBMCs were injected into SCID mice to mimic the human immune system. Then, the humanized SCID mice were challenged with M3-HHCC cells and immunized with nanoemulsion-encapsulated MAGE1-MAGE3-MAGEn/HSP70 [NE(M1M3MnH)] or M1M3MnH. The cellular immune responses were detected by IFN-γ ELISPOT and cytotoxicity assays. Therapeutic and tumor challenge experiments were also performed. RESULTS: The results showed that the immune responses elicited by NE(M1M3MnH) were apparently stronger than those elicited by M1M3MnH, NE(-) or PBS, suggesting that this novel nanoemulsion carrier induces potent antitumor immunity against the encapsulated antigens. The results of the therapeutic and tumor challenge experiments also indicated that the new vaccine had a definite effect on SCID mice bearing human hepatic cancer. CONCLUSION: Our study indicated that the combination of several tumor antigen-derived peptides may be a relatively good strategy for peptide-based cancer immunotherapy. These results suggest that the complex nanoemulsion vaccine could have broader applications for both therapy and prevention mediated by antitumor effects in the future.

Culturally Tailored Intervention to Promote Mammography Screening Practice Among Chinese American Women: a Systematic Review.

Our review aimed to assess the effectiveness of culturally tailored intervention in mammography practice for Chinese American women. We searched the entire paper published by the Cochrane Library, PubMed, and Web of Science from inception to 17 October 2019. Moreover, we manually checked reference lists of included studies to find other potentially eligible studies. It included clinical trials published in English that evaluated the effects of culturally tailored intervention on mammography practice for Chinese American women. Finally, we involved eight studies in our review. After the intervention, the mammography intention and breast cancer-related knowledge were significantly improved. However, there was no significant impact on mammography completion rate, perceived susceptibility, perceived seriousness, perceived benefits, perceived barriers, and Eastern cultural views of Chinese American women. The culturally tailored interventions could serve as promising approaches to improve mammography screening practice for Chinese American women, but further improvements are needed.

A small-molecule inhibitor of PCSK9 transcription ameliorates atherosclerosis through the modulation of FoxO1/3 and HNF1α.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that down-regulates hepatic low-density lipoprotein receptor (LDLR) by binding and shuttling LDLR to lysosomes for degradation. The development of therapy that inhibits PCSK9 has attracted considerable attention for the management of cardiovascular disease risk. However, only monoclonal antibodies of PCSK9 have reached the clinic use. Oral administration of small-molecule transcriptional inhibitors has the potential to become a therapeutic option. METHODS: Here, we developed a cell-based small molecule screening platform to identify transcriptional inhibitors of PCSK9. Through high-throughput screening and a series of evaluation, we found several active compounds. After detailed investigation on the pharmacological effect and molecular mechanistic characterization, 7030B-C5 was identified as a potential small-molecule PCSK9 inhibitor. FINDINGS: Our data showed that 7030B-C5 down-regulated PCSK9 expression and increased the total cellular LDLR protein and its mediated LDL-C uptake by HepG2 cells. In both C57BL/6 J and ApoE KO mice, oral administration of 7030B-C5 reduced hepatic and plasma PCSK9 level and increased hepatic LDLR expression. Most importantly, 7030B-C5 inhibited lesions in en face aortas and aortic root in ApoE KO mice with a slight amelioration of lipid profiles. We further provide evidences suggesting that transcriptional regulation of PCSK9 by 7030B-C5 mostly depend on the transcriptional factor HNF1α and FoxO3. Furthermore, FoxO1 was found to play an important role in 7030B-C5 mediated integration of hepatic glucose and lipid metabolism. INTERPRETATION: 7030B-C5 with potential suppressive effect of PCSK9 expression may serve as a promising lead compound for drug development of cholesterol/glucose homeostasis and cardiovascular disease therapy. FUND: This work was supported by grants from the National Natural Science Foundation of China (81473214, 81402929, and 81621064), the Drug Innovation Major Project of China (2018ZX09711001-003-006, 2018ZX09711001-007 and 2018ZX09735001-002), CAMS Innovation Fund for Medical Sciences (2016-I2M-2-002, 2016-I2M-1-011 and 2017-I2M-1-008), Beijing Natural Science Foundation (7162129).

AVP(4-8) Improves Cognitive Behaviors and Hippocampal Synaptic Plasticity in the APP/PS1 Mouse Model of Alzheimer's Disease.

Memory deficits with aging are related to the neurodegeneration in the brain, including a reduction in arginine vasopressin (AVP) in the brain of patients with Alzheimer's disease (AD). AVP(4-8), different from its precursor AVP, plays memory enhancement roles in the CNS without peripheral side-effects. However, it is not clear whether AVP(4-8) can improve cognitive behaviors and synaptic plasticity in the APP/PS1 mouse model of AD. Here, we investigated for the first time the neuroprotective effects of AVP(4-8) on memory behaviors and in vivo long-term potentiation (LTP) in APP/PS1-AD mice. The results showed that: (1) APP/PS1-AD mice had lower spontaneous alternation in the Y-maze than wild-type (WT) mice, and this was significantly reversed by AVP(4-8); (2) the prolonged escape latency of APP/PS1-AD mice in the Morris water maze was significantly decreased by AVP(4-8), and the decreased swimming time in target quadrant recovered significantly after AVP(4-8) treatment; (3) in vivo hippocampal LTP induced by high-frequency stimulation had a significant deficit in the AD mice, and this was partly rescued by AVP(4-8); (4) AVP(4-8) significantly up-regulated the expression levels of postsynaptic density 95 (PSD95) and nerve growth factor (NGF) in the hippocampus of AD mice. These results reveal the beneficial effects of AVP(4-8) in APP/PS1-AD mice, showing that the intranasal administration of AVP(4-8) effectively improved the working memory and long-term spatial memory of APP/PS1-AD mice, which may be associated with the elevation of PSD95 and NGF levels in the brain and the maintenance of hippocampal synaptic plasticity.

Preparation and Thermal Evaluation of Novel Polyimide Protective Coatings for Quartz Capillary Chromatographic Columns Operated over 320 °C for High-Temperature Gas Chromatography Analysis.

Protection of intrinsically brittle quartz chromatographic columns (CCs) from breakage or property deterioration in gas chromatography (GC) analysis has become an important research topic regarding high-temperature GC techniques. Polyimide (PI) has proved to be the most suitable protective coating for quartz CCs. In the current research, a series of novel high-temperature-resistant PI coatings for quartz CCs operated over 320 °C have been successfully prepared. For this purpose, the aromatic diamine with a rigid skeleton structure 2-(4-aminophenyl)-5-aminobenzimidazole (APBI) was copolymerized with two aromatic dianhydrides-3,3',4,4'-benzophenotetracarboxylic acid dianhydride (BTDA) and 4,4'-oxydiphthalic anhydride (ODPA)-and an aromatic diamine with flexible ether linkages-4,4'-oxydianiline (ODA)-by a two-step polymerization procedure via soluble poly(amic acid) (PAA) precursors, followed by thermal imidization at elevated temperatures. The developed PI coatings exhibited good comprehensive properties, including glass transition temperatures (Tg) as high as 346.9 °C, measured by dynamic mechanical analysis (DMA), and coefficients of linear thermal expansion (CTEs) as low as 24.6 × 10-6/K in the range of 50-300 °C. In addition, the PI coatings exhibited good adhesion to the fused quartz capillary columns. No cracking, delamination, warpage, or other failures occurred during the 100-cycle thermal shock test in the range of 25-320 °C.

Effects of urea plus nitrate pretreated rice straw and corn oil supplementation on fiber digestibility, nitrogen balance, rumen fermentation, microbiota and methane emissions in goats.

BACKGROUND: Urea pretreatment is an efficient strategy to improve fiber digestibility of low quality roughages for ruminants. Nitrate and oil are usually used to inhibit enteric methane (CH4) emissions from ruminants. The objective of this study was to examine the combined effects of urea plus nitrate pretreated rice straw and corn oil supplementation to the diet on nutrient digestibility, nitrogen (N) balance, CH4 emissions, ruminal fermentation characteristics and microbiota in goats. Nine female goats were used in a triple 3 × 3 Latin Square design (27 d periods). The treatments were: control (untreated rice straw, no added corn oil), rice straw pretreated with urea and nitrate (34 and 4.7 g/kg of rice straw on a dry matter [DM] basis, respectively, UN), and UN diet supplemented with corn oil (15 g/kg soybean and 15 g/kg corn were replaced by 30 g/kg corn oil, DM basis, UNCO). RESULTS: Compared with control, UN increased neutral detergent fiber (NDF) digestibility (P < 0.001) and copies of protozoa (P < 0.001) and R. albus (P < 0.05) in the rumen, but decreased N retention (-21.2%, P < 0.001), dissolved hydrogen concentration (-22.8%, P < 0.001), molar proportion of butyrate (-18.2%, P < 0.05), (acetate + butyrate) to propionate ratio (P < 0.05) and enteric CH4 emissions (-10.2%, P < 0.05). In comparison with UN, UNCO increased N retention (+34.9%, P < 0.001) and decreased copies of protozoa (P < 0.001) and methanogens (P < 0.001). Compared with control, UNCO increased NDF digestibility (+8.3%, P < 0.001), reduced ruminal dissolved CH4 concentration (-24.4%, P < 0.001) and enteric CH4 emissions (-12.6%, P < 0.05). CONCLUSIONS: A combination of rice straw pretreated with urea plus nitrate and corn oil supplementation of the diet improved fiber digestibility and lowered enteric CH4 emissions without negative effects on N retention. These strategies improved the utilization of rice straw by goats.