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Abstract 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.

ABSTRACT: 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.

An ultrahigh strain-independent damping in Mg–1Mn alloy was prepared by cold rolling process. Combined with microstructure characterization, the mechanical properties and damping capacities of Mg–1Mn alloy with different reduction were systematically investigated. By the appropriate cold rolling process, numerous parallel dislocations, stacking faults (SFs) and a few non-basal dislocations are introduced into Mg matrix. Due to the non-basal dislocations and stacking faults coexists with basal dislocations, their reaction with each other leads to the activation of more non-basal slips and increase of strain hardening rate, which simultaneously improves the strength and plasticity of Mg–1Mn alloy. On the other hand, the increase of number of moveable dislocations and SFs, acting as dissipated source, effectively improves the damping capacity. Especially, the Mg–1Mn alloy shows an ultrahigh strain-independent damping capacity, which outperforms the high-damping Mg-0.6Zr alloy. When the reduction is 20%, the alloys show a good comprehensive mechanical properties: the ultimate tensile strength (UTS), the yield strength (YS) and plasticity is 206 MPa, 156 MPa and 49.8%. This work provides a new strategy for preparing high-strength, high-plasticity and high-damping magnesium alloy.

Abstract 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.

Abstract 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

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). 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.

The effect of the lamellar long period stacking order (LPSO) phase on both mechanical properties and damping capacity of magnesium alloys is still vague. After heat treatment at 540 °C for 4 h and 450 °C for 10 h, the Mg-10Gd-2Y–1Zn-0.5Zr-0.2Nd (wt%) alloy with the lamellar LPSO phase is prepared to study the influence of lamellar LPSO phase on damping capacity and mechanical properties. Combined transmission electron microscopy (TEM) and scanning electron microscopy (SEM) equipped with electron back-scattering patterns (EBSD) system, it is surprisingly found that the growth direction of the lamellar LPSO phase on basal plane is nearly parallel to the slip direction of basal dislocations, which is benefit from dislocations movement on basal plane. The dislocations move on basal plane easily, lead to a relative high damping capacity. The alloy with LPSO phases shows higher ultimate tensile strength (UTS) and elongation (EL), increased from 234 MPa to 2.6% to 254 MPa and 4.6%, respectively. The lamellar LPSO phase has an attribution to UTS and EL due to its kink deformation mechanism. Therefore, the lamellar LPSO phase can be used as a functional phase to enhance the damping capacity and mechanical properties at the same time, and providing new ideas about preparing high-strength and high-damping magnesium alloy.

This research adopted the D-galactose induced senility mice as the research object, under the condition of constant energy control, different protein content of feeding groups was designed. Mice were under dietary intervention for 8 weeks, by analyzing the Morris water maze data, brain tissue slice and liver tissue antioxidant capacity to explore the anti-aging effect of protein nutrition in Guangxi longevity dietary patterns. The results showed that: Compared with the high (P/C=1/2), medium (P/C=1/3) and low (P/C=1/5) protein diet groups, the escape latency of mice in P/C=1/4 (protein/carbohydrate) group significantly decreased (P P/C=1/5 group > P/C=1/3 group > young control group > P/C=1/2 group > aging control group. In summary, mice in P/C=1/4 low-protein diet group can effectively resist the senior-induced injury of D-galactose, and maintain strong learning and memory ability and antioxidant ability, thus showing strong anti-aging effect. The results of this study would provide a theoretical basis for the relationship between dietary protein nutrition and health as well as longevity.

The activity of probiotic products would reduce to a certain extent during storage and in the gastrointestinal tract, resulting in weakened potential probiotic properties, in this study, Lactobacillus fermentum LTP1332 from the feces of centenarians in Bama, Guangxi was microencapsulated. In this experiment, gelatin (GEL) and chitosan (CS) were introduced for compounding based on sodium alginate (SA) and CaCl2 as the main wall materials. The key factors affecting the embedding rate were found by single-factor test, the radial basis function (RBF) was constructed by using Box-Behnken design (BBD), and the encapsulation process of Lactobacillus fermentum LTP1332 microcapsules was optimized by using genetic algorithms (GA). The optimized capsules were characterized using SEM scanning electron microscopy and other methods, and the in vitro simulated digestion tests was carried out. Results showed that, the optimum preparation parameters of the microcapsule were as follows: 2.210% sodium alginate, 4.451% CaCl2, 0.1% gelatin, 13.529 min curing time. Under such conditions, the measured average embedding rate was 95.08%±0.25%. The cell survival rate of CS-GEL-SA microcapsule under the optimized processing conditions could still reach 22.48%±0.78% after being treated with simulated gastric juice for 120 min. The maximum rate of probiotic release could be reached at 90 min of digestion with simulated intestinal juice, which had good intestinal solubility. Therefore, it is considered that the long-lived elderly source probiotic microcapsule prepared under this processing condition would have a good bacterial protection effect and good prospects in development and application.

Based on the previous study on the diet of the cohort of long-lived people in Guangxi, the recipes of long-lived people were summarized. In this study, eight representative dietary fiber complexes (DFC) with specific proportion in the recipes were extracted by ultrasonic assisted enzyme method, and the optimal conditions of extraction process were explored through single factor and response surface tests, the basic components and physical and chemical properties were analyzed. The results showed that the maximum yield of total dietary fiber (TDF) was 63.90%, which was basically consistent with the theoretical prediction when the addition of α-amylase was 0.3%, the ultrasonic power was 242 W, the liquid-solid ratio was 15 mL/g and the extraction temperature was 86 ℃. After optimization, the contents of protein, fat and other impurities in TDF decreased from (2.66%±0.12%) and (5.31%±0.14%) to (1.90%±0.08%) and (1.77%±0.26%) respectively, and the content of TDF increased significantly (P

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.

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.

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].

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

Abstract In this paper, we prove the existence of positive ground state solutions of the Schrödinger–Poisson system involving a negative nonlocal term and critical exponent on a bounded domain. The main tools are the mountain pass theorem and the concentration compactness principle.

For electrochromic materials to reach their full potential for high efficiency bistable displays, technical challenges related to their underlying mechanism must be addressed. Here, the authors, through intelligent molecular design, report a solid bistable device with state-of-the-art performance.

Abstract We study the Hölder continuity of weak solution u to an equation arising in the stationary motion of electrorheological fluids. To this end, we first obtain higher integrability of Du in our case by establishing a reverse Hölder inequality. Next, based on the result of locally higher integrability of Du and difference quotient argument, we derive a Nikolskii type inequality; then in view of the fractional Sobolev embedding theorem and a bootstrap argument we obtain the main result. Here, the analysis and the existence theory of a weak solution to our equation are similar to the weak solution which has been established in the literature with 3dd+2≤p∞≤p(x)≤p0