Improved Photodynamic Therapy Based on Glutaminase Blockage via Tumor Membrane Coated CB-839/IR-780 Nanoparticles.

Photodynamic therapy (PDT) has promising applications. However, the lethal function of reactive oxygen species (ROS) produced during PDT is typically limited. This restriction is induced by oxygen shortage in the tumor microenvironment due to tumor cell hypermetabolism and reductive chemicals overexpression in tumor tissues. Glutamine (Gln) metabolism is crucial for malignancy development and is closely associated with redox. Herein, a novel nanoparticle (NP) named IRCB@M is constructed to boost PDT through dual effects. This NP simultaneously blocks aerobic respiration and inhibits cellular reduced substances by blocking the Gln metabolic pathway. Within the nanocomplex, a photosensitizer (IR-780) and a glutaminase inhibitor (CB-839) are self-assembled and then encapsulated by cancer cell membranes for homologous targeting. The Gln metabolism intervention relieves hypoxia and decreases the levels of nicotinamide adenine dinucleotide phosphate (NADPH) as well as reduced glutathione (GSH) in vitro and in vivo, which are the dual amplification effects on the IR-780-mediated lethal PDT. The antitumor effects against gastric cancer are ultimately evoked in vivo, thus offering a novel concept for enhancing PDT and other ROS-dependent therapeutic approaches.

Evidence from an Avian Embryo Model that Zinc-Inducible MT4 Expression Protects Mitochondrial Function Against Oxidative Stress.

BACKGROUND: Metallothioneins (MTs) have a strong affinity for zinc (Zn) and remain at a sufficiently high level in mitochondria. As the avian embryo is highly susceptible to oxidative damage and relatively easy to manipulate in a naturally closed chamber, it is an ideal model of the effects of oxidative stress on mitochondrial function. However, the protective roles and molecular mechanisms of Zn-inducible protein expression on mitochondrial function in response to various stressors are poorly understood. OBJECTIVES: The study aimed to investigate the mechanisms by which Zn-induced MT4 expression protects mitochondrial function and energy metabolism subjected to oxidative stress using the avian embryo and embryonic primary hepatocyte models. METHODS: First, we investigated whether MT4 expression alters mitochondrial function. Then, we examined the effects of Zn-induced MT4 overexpression and MT4 silencing on embryonic primary hepatocytes from breeder hens fed a normal Zn diet subjected to a tert-butyl hydroperoxide (BHP) oxidative stress challenge during incubation. In vivo, the avian embryos from hens fed the Zn-deficient and Zn-adequate diets were used to determine the protective roles of Zn-induced MT4 expression on the function of mitochondria exposed to oxidative stress induced by in ovo BHP injection. RESULTS: An in vitro study revealed that Zn-induced MT4 expression reduced reactive oxygen species accumulation in primary hepatocytes. MT4 silencing exacerbated BHP-mediated mitochondrial dysfunction whereas Zn-inducible MT4 overexpression mitigated it. Another in vivo study disclosed that maternal Zn-induced MT4 expression protected mitochondrial function in chick embryo hepatocytes against oxidative stress by inhibiting the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)/peroxisome proliferators-activated receptor-γ (PPAR-γ) pathway. CONCLUSION: This study underscores the potential protective roles of Zn-induced MT4 expression via the downregulation of the PGC-1α/PPAR-γ pathway on mitochondrial function stimulated by the stress challenge in the primary hepatocytes in an avian embryo model. Our findings suggested that Zn-induced MT4 expression could provide a new therapeutic target and preventive strategy for repairing mitochondrial dysfunction in disease.

Gut Microbe-Metabolite Profiles Are Associated with Microbial Pathways of Longevity in Women: A Cross-Sectional Study Conducted in China.

INTRODUCTION: Recent research on the gut deepens people's understanding of the role of gut microbe-metabolites in longevity. However, most of the longevity population is female, and the gut microbe-metabolites associated with longevity in women remain unknown. Here, we hypothesize that the gut microbe-metabolite levels differed between the longevity women (LW, age ≥90) and the elderly women (EW, 60 < age <90). METHODS: We performed a cross-sectional study of 22 women in Guangxi longevity areas. 16S rRNA full-length sequencing, bioinformatic analysis, and nuclear magnetic resonance hydrogen spectra were determined to analyze the gut microbiota, microbial pathways, and fecal metabolites. We evaluated significant differences and relationships in gut microbe-metabolites and microbial pathways using the Mann-Whitney test and Spearman correlation, respectively. RESULTS: The EW experienced gut dysbiosis characterized by a higher Firmicutes/Bacteroidetes (F/B) value. The LW showed a higher abundance of Bacteroides and Alistipes, which might support health maintenance. Moreover, LW enriched alanine, aspartate, and glutamate metabolism, histidine metabolism, and pyruvate metabolism, leading to major changes in histidine, fumaric acid, acetate, valine, and aspartate. Interestingly, the most valuable metabolic pathway based on differential fecal metabolites confirmed the KEGG microbial pathway "alanine, aspartate, and glutamate metabolism" enriched in LW. Impressively, Bacteroides and Alistipes were positively correlated with alanine, aspartate, and glutamate metabolism, thus improving the level of aspartate, which could be a particular pathway related to longevity. CONCLUSION: The enriched gut genus and microbial pathways in LW showed a significant correlation, which might mediate the production of metabolites related to longevity.

A multicolour bistable electronic shelf label based on intramolecular proton-coupled electron transfer.

Bistable electrochromic materials have been explored as a viable alternative to reduce energy consumption in display applications. However, the development of ideal bistable electrochromic displays (especially multicolour displays) remains challenging due to the intrinsic limitations associated with existing electrochromic processes. Here, a bistable electrochromic device with good overall performance-including bistability (>52 h), reversibility (>12,000 cycles), colouration efficiency (≥1,240 cm2 C-1) and transmittance change (70%) with fast switching (≤1.5 s)-was designed and developed based on concerted intramolecular proton-coupled electron transfer. This approach was used to develop black, magenta, yellow and blue displays as well as a multicolour bistable electrochromic shelf label. The design principles derived from this unconventional exploration of concerted intramolecular proton-coupled electron transfer may also be useful in different optoelectronic applications.

Platycodin D, a triterpenoid saponin from Platycodon grandiflorum, suppresses the growth and invasion of human oral squamous cell carcinoma cells via the NF-κB pathway.

This work was undertaken to explore the effects of platycodin D, a triterpenoid saponin from Platycodon grandiflorum, on the growth and invasiveness of human oral squamous cell carcinoma (OSCC). Platycodin D caused a significant, concentration-dependent inhibition of cell viability and induced significant apoptosis in OSCC cells. Moreover, platycodin D significantly inhibited OSCC cell invasion. At the molecular level, platycodin D increased the amounts of IκBα protein and reduced the expression of phosphorylated NF-κB p65, MMP-2, and MMP-9. Ectopic expression of constitutively active NF-κB p65 prevented platycodin D-mediated induction of apoptosis and suppression of invasion in OSCC cells. In vivo studies confirmed that platycodin D retarded the growth of subcutaneous SCC-4 xenograft tumors and reduced phosphorylation of NF-κB p65. Altogether, platycodin D shows inhibitory activity on OSCC growth and invasion through inactivation of the NF-κB pathway and might provide therapeutic benefits in the treatment of OSCC.

Causal effect between gut microbiota and metabolic syndrome in European population: a bidirectional mendelian randomization study.

BACKGROUND: Observational studies have reported that gut microbiota composition is associated with metabolic syndrome. However, the causal effect of gut microbiota on metabolic syndrome has yet to be confirmed. METHODS: We performed a bidirectional Mendelian randomization study to investigate the causal effect between gut microbiota and metabolic syndrome in European population. Summary statistics of gut microbiota were from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium. The summary statistics of outcome were obtained from the most comprehensive genome-wide association studies of metabolic syndrome (n = 291,107). The inverse-variance weighted method was applied as the primary method, and the robustness of the results was assessed by a series of sensitivity analyses. RESULTS: In the primary causal estimates, Actinobacteria (OR = 0.935, 95% CI = 0.878-0.996, P = 0.037), Bifidobacteriales (OR = 0.928, 95% CI = 0.868-0.992, P = 0.028), Bifidobacteriaceae (OR = 0.928, 95% CI = 0.868-0.992, P = 0.028), Desulfovibrio (OR = 0.920, 95% CI = 0.869-0.975, P = 0.005), and RuminococcaceaeUCG010 (OR = 0.882, 95% CI = 0.803-0.969, P = 0.009) may be associated with a lower risk of metabolic syndrome, while Lachnospiraceae (OR = 1.130, 95% CI = 1.016-1.257, P = 0.025), Veillonellaceae (OR = 1.055, 95% CI = 1.004-1.108, P = 0.034) and Olsenella (OR = 1.046, 95% CI = 1.009-1.085, P = 0.015) may be linked to a higher risk for metabolic syndrome. Reverse MR analysis demonstrated that abundance of RuminococcaceaeUCG010 (OR = 0.938, 95% CI = 0.886-0.994, P = 0.030) may be downregulated by metabolic syndrome. Sensitivity analyses indicated no heterogeneity or horizontal pleiotropy. CONCLUSIONS: Our Mendelian randomization study provided causal relationship between specific gut microbiota and metabolic syndrome, which might provide new insights into the potential pathogenic mechanisms of gut microbiota in metabolic syndrome and the assignment of effective therapeutic strategies.

Enhanced Photodynamic Therapy Synergizing with Inhibition of Tumor Neutrophil Ferroptosis Boosts Anti-PD-1 Therapy of Gastric Cancer.

For tumor treatment, the ultimate goal in tumor therapy is to eliminate the primary tumor, manage potential metastases, and trigger an antitumor immune response, resulting in the complete clearance of all malignant cells. Tumor microenvironment (TME) refers to the local biological environment of solid tumors and has increasingly become an attractive target for cancer therapy. Neutrophils within TME of gastric cancer (GC) spontaneously undergo ferroptosis, and this process releases oxidized lipids that limit T cell activity. Enhanced photodynamic therapy (PDT) mediated by di-iodinated IR780 (Icy7) significantly increases the production of reactive oxygen species (ROS). Meanwhile, neutrophil ferroptosis can be triggered by increased ROS generation in the TME. In this study, a liposome encapsulating both ferroptosis inhibitor Liproxstatin-1 and modified photosensitizer Icy7, denoted LLI, significantly inhibits tumor growth of GC. LLI internalizes into MFC cells to generate ROS causing immunogenic cell death (ICD). Simultaneously, liposome-deliver Liproxstatin-1 effectively inhibits the ferroptosis of tumor neutrophils. LLI-based immunogenic PDT and neutrophil-targeting immunotherapy synergistically boost the anti-PD-1 treatment to elicit potent TME and systemic antitumor immune response with abscopal effects. In conclusion, LLI holds great potential for GC immunotherapy.

The developmental pattern related to fatty acid uptake and oxidation in the yolk sac membrane and jejunum during embryogenesis in Muscovy duck.

This study aimed to investigate the developmental change of body growth and gene expression related to fatty acid uptake and oxidation in the yolk sac membrane (YSM) and jejunum during embryogenesis in Muscovy ducks. The weights of embryos and yolk sac (YS) (5 embryos per replicate, n = 6) were recorded on embryonic days (E)16, E19, E22, E25, E28, E31, and the day of hatch (DOH). The fat and fatty acid contents in YSM, jejunal histology, and gene expression related to fatty acid metabolism in YSM and jejunum were determined in each sampling time. Among the nonlinear models, the maximum growth is estimated at 2.83 (E22.5), 2.67 (E22.1), and 2.60 (E21.3) g/d using logistic, Gompertz, and Von Bertalanffy models, respectively. The weight of YS, and ether extract-free YS as well as the amounts of fat and fatty acids in YS decreased (P < 0.05) linearly, whereas the villus height, crypt depth, villus height/crypt depth, and musculature thickness in jejunum increased (P < 0.05) linearly during embryogenesis. The mRNA expression of CD36, SLC27A4, and FABP1 related to fatty acid uptake as well as the mRNA and protein expressions of PPARα and CPT1 related to fatty acid oxidation increased in a quadratic manner (P < 0.05) in both YS and jejunum, and the maximum values were achieved during E25 to E28. In conclusion, the maximum growth rate of Muscovy duck embryos was estimated at 2.60 to 2.83 g/d on E21.3 to E23.5, while the accumulations of lipid and fatty acid in YS were decreased in association with the increased absorptive area of morphological structures in jejunum. The gene and protein expression involved in fatty acid metabolism displayed a similar enhancement pattern between YSM and jejunum during E25 to E28, suggesting that fatty acid utilization could be strengthened to meet the energy demand for embryonic development.

Effect of Frame Rate on User Experience, Performance, and Simulator Sickness in Virtual Reality.

The refresh rate of virtual reality (VR) head-mounted displays (HMDs) has been growing rapidly in recent years because of the demand to provide higher frame rate content as it is often linked with a better experience. Today's HMDs come with different refresh rates ranging from 20Hz to 180Hz, which determines the actual maximum frame rate perceived by users' naked eyes. VR users and content developers often face a choice because having high frame rate content and the hardware that supports it comes with higher costs and other trade-offs (such as heavier and bulkier HMDs). Both VR users and developers can choose a suitable frame rate if they are aware of the benefits of different frame rates in user experience, performance, and simulator sickness (SS). To our knowledge, limited research on frame rate in VR HMDs is available. In this paper, we aim to fill this gap and report a study with two VR application scenarios that compared four of the most common and highest frame rates currently available (60, 90, 120, and 180 frames per second (fps)) to explore their effect on users' experience, performance, and SS symptoms. Our results show that 120fps is an important threshold for VR. After 120fps, users tend to feel lower SS symptoms without a significant negative effect on their experience. Higher frame rates (e.g., 120 and 180fps) can ensure better user performance than lower rates. Interestingly, we also found that at 60fps and when users are faced with fast-moving objects, they tend to adopt a strategy to compensate for the lack of visual details by predicting or filling the gaps to try to meet the performance needs. At higher fps, users do not need to follow this compensatory strategy to meet the fast response performance requirements.

Developmental changes in lipid and fatty acid metabolism and the inhibition by in ovo feeding oleic acid in Muscovy duck embryogenesis.

Hepatic lipid and fatty acid (FA) metabolism are critical for regulating energetic homeostasis during embryogenesis. At present, it remains unclear how an exogenous FA intervention affects embryonic development in an avian embryo model. In Exp. 1, 30 fertilized eggs were sampled on embryonic days (E) 16, 19, 22, 25, 28, 31 and the day of hatch (DOH) to determine the critical period of lipid metabolism. In Exp. 2, a total of 120 fertilized eggs were divided into two groups (60 eggs/group) for in ovo feeding (IOF) procedures on E25. Eggs were injected into the yolk sac with PBS as the control group and with oleic acid (OA) as the IOF-OA treatment group. Samples were collected on E28 and E31. In Exp. 1, hepatic triacylglycerol (TG) and cholesterol (CHO) contents increased while serum TG content decreased from E16 to DOH (P < 0.05). Both serum and liver displayed an increase in unsaturated FA and a decrease in saturated FA (P < 0.05). There was a quadratic increase in the target gene and protein expression related to hepatic FA de novo synthesis and oxidation (P < 0.05), whose inflection period was between E22 and E28. In Exp. 2, compared with the control embryos, IOF-OA embryos had an increased yolk sac TG content on E28 and E31, and a decreased serum TG and CHO content on E28 (P < 0.05). The IOF-OA embryos had less OA in the yolk sac and liver on E28, and less unsaturated FA in the serum and liver on E31 than did the control embryos (P < 0.05). Hepatic gene mRNA expression related to FA uptake, synthesis, and oxidation on E28 was lower in IOF-OA than in control embryos (P < 0.05), not on E31 (P > 0.05). Maximal metabolic changes in lipid and FA metabolism occurred on E22-E28 in Muscovy duck embryogenesis, along with the altered target gene and protein expression related to lipogenesis and lipolysis. IOF-OA intervention on E25 could inhibit the target gene expression related to FA uptake, synthesis, and oxidation, which may influence the normal FA metabolism on E28 during embryogenesis.

Maternal zinc alleviates tert-butyl hydroperoxide-induced mitochondrial oxidative stress on embryonic development involving the activation of Nrf2/PGC-1α pathway.

BACKGROUND: Mitochondrial dysfunction induced by excessive mitochondrial reactive oxygen species (ROS) damages embryonic development and leads to growth arrest. OBJECTIVE: The purpose of this study is to elucidate whether maternal zinc (Zn) exert protective effect on oxidative stress targeting mitochondrial function using an avian model. RESULT: In ovo injected tert-butyl hydroperoxide (BHP) increases (P < 0.05) hepatic mitochondrial ROS, malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG), and decreases (P < 0.05) mitochondrial membrane potential (MMP), mitochondrial DNA (mtDNA) copy number and adenosine triphosphate (ATP) content, contributing to mitochondrial dysfunction. In vivo and in vitro studies revealed that Zn addition enhances (P < 0.05) ATP synthesis and metallothionein 4 (MT4) content and expression as well as alleviates (P < 0.05) the BHP-induced mitochondrial ROS generation, oxidative damage and dysfunction, exerting a protective effect on mitochondrial function by enhancing antioxidant capacity and upregulating the mRNA and protein expressions of Nrf2 and PGC-1α. CONCLUSIONS: The present study provides a new way to protect offspring against oxidative damage by maternal Zn supplementation through the process of targeting mitochondria involving the activation of Nrf2/PGC-1α signaling.

Longevity-Associated Core Gut Microbiota Mining and Effect of Mediated Probiotic Combinations on Aging Mice: Case Study of a Long-Lived Population in Guangxi, China.

With an ageing population, healthy longevity is becoming an important scientific concern. The longevity phenomenon is closely related to the intestinal microflora and is highly complicated; it is challenging to identify and define the core gut microbiota associated with longevity. Therefore, in this study, 16S rRNA sequencing data were obtained from a total of 135 faecal samples collected as part of the latest sampling and pre-collection initiative in the Guangxi longevity area, and weighted gene co-expression network analysis (WGCNA) was used to find a mediumpurple3 network module significantly associated with the Guangxi longevity phenomenon. Five core genera, namely, Alistipes, Bacteroides, Blautia, Lachnospiraceae NK4A136 group, and Lactobacillus, were identified via network analysis and random forest (RF) in this module. Two potential probiotic strains, Lactobacillus fermentum and Bacteroides fragilis, were further isolated and screened from the above five core genera, and then combined and used as an intervention in naturally ageing mice. The results show a change in the key longevity gut microbiota in mice toward a healthy longevity state after the intervention. In addition, the results show that the probiotic combination effectively ameliorated anxiety and necrosis of hippocampal neuronal cells in senescent mice, improving their antioxidant capacity and reducing their inflammation levels. In conclusion, this longer-term study provides a new approach to the search for longevity hub microbiota. These results may also provide an important theoretical reference for the healthification of the intestinal microflora in the general population, and even the remodelling of the structure of the longevity-state intestinal microflora.

Pannexin 1 forms an anion-selective channel.

Pannexin 1 (Panx1) is expressed in various mammalian tissues including the brain and immune cells. Here, we present evidence that Panx1 when expressed in mammalian cells, forms anion-selective channels, with a rank order of permeabilities: NO (3) (-)> I(-) > Br (-)> Cl (-) > F (-)>> aspartate (-)≈ glutamate (-)≈ gluconate(-). Single-channel Panx1-mediated currents have a unitary conductance around 68 pS. Our results show that Panx1 assembles into a membrane anion channel with a relatively low single-channel conductance.

Effect of dietary protein content shift on aging in elderly rats by comprehensive quantitative score and metabolomics analysis.

In the protein nutrition strategy of middle-aged and elderly people, some believe that low protein is good for health, while others believe high protein is good for health. Facing the contradictory situation, the following hypothesis is proposed. There is a process of change from lower to higher ratio of protein nutritional requirements that are good for health in the human body after about 50 years of age, and the age at which the switch occurs is around 65 years of age. Hence, in this study, 50, 25-month-old male rats were randomly divided into five groups: Control (basal diet), LP (low-protein diet with a 30% decrease in protein content compared to the basal diet), HP (high-protein diet with a 30% increase in protein content compared to the basal diet), Model 1 (switched from LP to HP feed at week 4), and Model 2 (switched from LP to HP feed at week 7). After a total of 10 weeks intervention, the liver and serum samples were examined for aging-related indicators, and a newly comprehensive quantitative score was generated using principal component analysis (PCA). The effects of the five protein nutritional modalities were quantified in descending order: Model 1 > HP > LP > Control > Model 2. Furthermore, the differential metabolites in serum and feces were determined by orthogonal partial least squares discriminant analysis, and 15 differential metabolites, significantly associated with protein intake, were identified by Spearman's correlation analysis (p < 0.05). Among the fecal metabolites, 10 were positively correlated and 3 were negatively correlated. In the serum, tyrosine and lactate levels were positively correlated, and acetate levels were negatively correlated. MetaboAnalyst analysis identified that the metabolic pathways influenced by protein intake were mainly related to amino acid and carbohydrate metabolism. The results of metabolomic analysis elucidate the mechanisms underlying the preceding effects to some degree. These efforts not only contribute to a unified protein nutrition strategy but also positively impact the building of a wiser approach to protein nutrition, thereby helping middle-aged and older populations achieve healthy aging.

Responses of Combined Non-starch Polysaccharide Enzymes and Protease on Growth Performance, Meat Quality, and Nutrient Digestibility of Yellow-Feathered Broilers Fed With Diets With Different Crude Protein Levels.

The aim of this study was to investigate the responses of non-starch polysaccharide (NSP) enzymes and protease combination on growth performance, meat quality, and nutrients digestibility of yellow-feathered broilers fed with corn-soybean meal basal diets with normal and subnormal crude protein (CP) levels. The experimental design was completely randomized with a 2 × 2 factorial arrangement of treatments, including six replicates of 20 birds per pen. Two basal diets were formulated with normal CP level as positive control (PC) and subnormal CP level without extra essential amino acid (AA) supplementation as negative control (NC). The basal diets were supplemented without or with NSP enzymes and protease. Broilers fed with the NC diet had lower (P < 0.05) final body weight (BW), average daily weight gain (ADG) on days 1-21, 22-56 and 1-56 and higher (P < 0.05) feed-to-gain ratio (F/G) on day 22-56 than those fed with PC diet. The broilers fed with the NC diet had higher (P < 0.05) L* and b* values in thigh muscle, crypt depth in the duodenum, and dry matter (DM) digestibility as well as lower (P < 0.05) villus height, musculature thicknesses, and villus height: crypt depth in the duodenum than those fed with the PC diet. Dietary NSP enzymes and protease combination increased (P < 0.05) the ADG and F/G of the broilers on days 1-56, and pH values in breast and thigh muscles as well as the digestibility of DM, gross energy (GE), CP and most AAs of the broilers on day 56. Compared with the PC diet, the combination of NSP enzymes and protease exhibited greater (P < 0.05) improvements in the digestibility of DM, CP, and some AAs (Asp, Ile, and Leu) in the broilers fed with the NC diet. In conclusion, reducing CP diet without essential AA supplementation impaired the growth performance and meat color of the thigh muscles of the broilers. The combination of NSP enzymes and protease effectively improved the growth performance, meat quality, and nutritional values of the broilers. In terms of the digestibility of DM, CP, and some AAs, the magnitude of response to the addition of NSP enzymes and protease was greater in the low nutritional-quality diet with a subnormal CP level.

A Clinical Trial of the Effects of a Dietary Pattern on Health Metrics and Fecal Metabolites in Volunteers With Risk of Cardiovascular Disease.

The phenomenon of longevity in Guangxi of China proved to be closely relevant to its specific dietary habits, but the exact effects of this diet on health remain to be explored. In this work, fourteen screened volunteers with cardiovascular disease (CVD) risk followed a novel dietary pattern derived from centenarians of Guangxi, China for 2 weeks, then the effects of diet on human health were explored by measuring the health metrics and fecal metabolites. The results showed that the short-term dietary intervention significantly decreased the body weight, body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), mean systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels, while it significantly increased high-density lipoprotein cholesterol (HDL-c) levels. Orthogonal partial least squares discriminant analysis (OPLS-DA) indicated a distinct separation in the fecal metabolic profiles of volunteers before and after the intervention. Nine of these metabolites showed significant differences, including two metabolites increased (butyrate and citrulline), seven metabolites decreased (threonine, choline, glycine, aspartate, alanine, N-acetylglutamic acid and lysine). Pathway and enrichment analysis showed that the reduction in CVD risk by dietary intervention mainly affected five pathways, which include arginine biosynthesis; aminoacyl-tRNA biosynthesis; glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; and valine, leucine and isoleucine biosynthesis. Herein, the Guangxi longevity dietary pattern can provide a feasible healthy diet strategy for reducing the CVD risk and human beings. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR220 0058216].

Exogenous Linoleic Acid Intervention Alters Hepatic Glucose Metabolism in an Avian Embryo Model.

In the present study, developmental changes of gluconeogenesis and glycolysis in an avian model were measured, and then the intervention effects of in ovo feeding (IOF) linoleic acid (LA) on hepatic glucose metabolism were evaluated. In Experiment 1, thirty fertilized eggs were sampled on embryonic days (E) of 16, 19, 22, 25, 28, 31, and thirty newly-hatched ducklings at hatch (E34 and E35). In Experiment 2, a total of 120 fertilized eggs (60 eggs for each group) were injected into the yolk sac with PBS as the control group and LA as the IOF LA group on E25. Twelve eggs were selected for sample collection on E28 and E31. Serum contents of glucose, pyruvate, and lactate increased ( p < 0.05) linearly or quadratically from E16 to hatch, as well as hepatic glycogen and pyruvate contents. Hepatic mRNA expression related to energy homeostasis, gluconeogenesis, and glycolysis increased ( p < 0.05) in embryogenesis, and the plateau period was presented on E25-E31. IOF LA decreased ( p < 0.05) serum contents of glucose, triacylglycerol, cholesterol, and hepatic oleic acid, unsaturated fatty acids on E28, as well as the gene expression relative to gluconeogenesis. IOF LA increased ( p < 0.05) pyruvate content in serum and liver, and hepatic gene expression relative to glycolysis on E31. In summary, hepatic gluconeogenesis and glycolysis were enhanced to meet the increasing energy demands of embryonic development during E25 - hatch. Exogenous LA intervention on E25 could inhibit hepatic gluconeogenesis and enhance glycolysis during the later developmental period, disrupting glucose embryonic homeostasis and energy status.

A Pilot Study of the Effect of Lactobacillus casei Obtained from Long-Lived Elderly on Blood Biochemical, Oxidative, and Inflammatory Markers, and on Gut Microbiota in Young Volunteers.

Probiotic intake has been shown to improve certain physiological health indicators. We aimed to examine effects of Lactobacillus casei LTL1879, obtained from long-lived elderly volunteers, on blood biochemical, oxidative, and inflammatory markers and gut microbiota in twenty healthy, young volunteers. Volunteers were randomly divided into equal probiotic and placebo groups and changes in blood biochemical indicators, oxidative and inflammatory markers, and gut microbiota were examined after three weeks of probiotic intervention. The probiotic group's antioxidant levels were significantly enhanced post-intervention. Total antioxidant capacity (T-AOC) levels were significantly increased (p < 0.0001), while malondialdehyde (MDA) levels decreased (p < 0.05), and total superoxide dismutase (T-SOD) levels increased, but with no significant difference. In addition, Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) levels were significantly up-regulated and down-regulated (p < 0.05, respectively). Escherichia coli, Enterococcus, and Bacteroides expression was significantly reduced (p < 0.05), while Clostridium leptum, Bifidobacterium, and Lactobacillus expression increased (p < 0.05). Volunteer health status was quantified using principal components and cluster analysis, indicating that the probiotic group's overall score was higher than that of the placebo group. The results of this pilot study suggest L. casei LTL 1879 can significantly improve specific immune, oxidative, and gut microbiota characteristics related to health factors.

Bio-inspired ultra-high energy efficiency bistable electronic billboard and reader.

Bistable display has been a long-awaited goal due to its zero energy cost when maintaining colored or colorless state and electrochromic material has been highly considered as a potential way to achieve bistable display due to its simple structure and possible manipulation. However, it is extremely challenging with insurmountable technical barriers related to traditional electrochromic mechanisms. Herein a prototype for bistable electronic billboard and reader with high energy efficiency is demonstrated with excellent bistability (decay 7% in an hour), reversibility (104 cycles), coloration efficiency (430 cm2 C-1) and very short voltage stimulation time (2 ms) for color switching, which greatly outperforms current products. This is achieved by stabilization of redox molecule via intermolecular ion transfer to the supramolecular bonded colorant and further stabilization of the electrochromic molecules in semi-solid media. This promising approach for ultra-energy-efficient display will promote the development of switching molecules, devices and applications in various fields of driving/navigation/industry as display to save energy.