Effect of Wu Zhi San supplementation in LPS-induced intestinal inflammation and barrier damage in broilers

Intestinal inflammation and barrier damage can inhibit the absorption and transportation of nutrients in the small intestine, and lead to various chronic diseases. Wu Zhi San (WZS) is a traditional Chinese formula composed of Schisandrae, Anemarrhenae, Lonicerae, and Glycyrrhizae that was made to cure intestinal inflammation and barrier damage in broilers. To evaluate the protective effect of WZS on intestinal inflammation and barrier damage of broilers under lipopolysaccharide (LPS) stress, a total of 200 one-day-old broilers were randomly divided into five groups, namely, the CON group, LPS group, and three WZS groups (WZS-H, WZS-M, and WZS-L). The groups were designed for stress phase I (days 15, 17, 19, and 21) and stress phase II (days 29, 31, 33, and 35). The protective effect of WZS on the intestinal tract was evaluated by measuring the levels of serum myeloperoxidase (MPO), diamine oxidase (DAO), super oxide dismutase (SOD), and serum D-lactate (D-LA) and the expression of inflammatory factors in jejunum. The results showed that the diet supplemented with WZS could significantly reduce serum MPO, DAO, and D-LA levels and jejunal CD in broilers (p < 0.05), increase serum SOD levels and jejunal VH (p < 0.05), significantly downregulate the expression of NF-κB, TLR4, MyD88, and inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10), and upregulate Claudin-1, Occludin-1, and ZO-1 in broiler jejunum mucosa (p < 0.05). On the other hand, WZS could significantly reduce the protein expression of NF-κB (p65) in broiler jejunum (p < 0.05). These results indicate that supplementing WZS in the diet can reduce intestinal inflammation and alleviate intestinal barrier damage, and by inhibiting the NF-κB/TLR4/MyD88 signaling pathway, supplementation with WZS intervenes in LPS-induced stress injury in broilers

Metabolic Rewiring of Macrophages Promotes Anti-Tumor Activity in Pancreatic Cancer

Macrophages abound in the tumor microenvironment of pancreatic cancer and other solid malignancies. Although macrophages typically promote tumorigenesis, they also represent key targets for immunotherapy approaches, which aim to: 1) deplete macrophages, 2) inhibit their activity, or 3) redirect them toward an anti-tumor role. Redirecting macrophages is commonly described as a phenotypic shift from M2 (anti-inflammatory) to M1 (pro-inflammatory) polarization. However, macrophage phenotypes have grown increasingly diverse and only loosely describe functional roles. Here we examine the anti-tumor functions of macrophages – their ability to engulf and kill tumor cells – and the metabolic dependencies of this process, using a syngeneic and fully immunocompetent tumor model of pancreatic ductal adenocarcinoma (PDAC). In PDAC cells derived from KPC (KrasLSL.G12D/+; Trp53R172H/+; Pdx-Cre) mice, the anti-phagocytic receptor CD47 was knocked out using transient CRISPR-Cas9 expression. CD47 is overexpressed by tumor cells to suppress macrophage anti-tumor activity and escape cancer immunosurveillance. Despite the critical role of CD47, we found that complete loss of CD47 in PDAC cells did not induce macrophage engulfment in vitro , nor did it impact tumor growth in vivo. We hypothesized that macrophages required an activated state, and found that ODN1826, a CpG oligonucleotide, could stimulate macrophages to engulf tumor cells whether they expressed CD47 or not, and without inducing classical M1 or M2 markers. Moreover, CpG treatment of tumor-bearing mice induced potent anti-tumor responses that required macrophages, but not lymphocytes, natural killer cells, or dendritic cells. CpG activation was found to promote oxidative respiration dependent on fatty acid oxidation, along with rewiring of the Krebs cycle through the activity of ATP citrate lyase. Together, these changes represented a hybrid of M1 and M2 metabolisms, and were critical for macrophage engulfment of PDAC cells and anti-tumor activity. Our findings indicate that immune activation of macrophages alter their metabolic state rather than their M1/M2 phenotype to enable them to overcome inhibitory CD47 and carry out anti-tumor activity

Metabolic Rewiring Of Macrophages Promotes Anti-Tumor Activity In Pancreatic Cancer

Macrophages abound in the tumor microenvironment of pancreatic cancer and other solid malignancies. Although macrophages typically promote tumorigenesis, they also represent key targets for immunotherapy approaches, which aim to: 1) deplete macrophages, 2) inhibit their activity, or 3) redirect them toward an anti-tumor role. Redirecting macrophages is commonly described as a phenotypic shift from M2 (anti-inflammatory) to M1 (pro-inflammatory) polarization. However, macrophage phenotypes have grown increasingly diverse and only loosely describe functional roles. Here we examine the anti-tumor functions of macrophages – their ability to engulf and kill tumor cells – and the metabolic dependencies of this process, using a syngeneic and fully immunocompetent tumor model of pancreatic ductal adenocarcinoma (PDAC). In PDAC cells derived from KPC (KrasLSL.G12D/+; Trp53R172H/+; Pdx-Cre) mice, the anti-phagocytic receptor CD47 was knocked out using transient CRISPR-Cas9 expression. CD47 is overexpressed by tumor cells to suppress macrophage anti-tumor activity and escape cancer immunosurveillance. Despite the critical role of CD47, we found that complete loss of CD47 in PDAC cells did not induce macrophage engulfment in vitro, nor did it impact tumor growth in vivo. We hypothesized that macrophages required an activated state, and found that ODN1826, a CpG oligonucleotide, could stimulate macrophages to engulf tumor cells whether they expressed CD47 or not, and without inducing classical M1 or M2 markers. Moreover, CpG treatment of tumor-bearing mice induced potent anti-tumor responses that required macrophages, but not lymphocytes, natural killer cells, or dendritic cells. CpG activation was found to promote oxidative respiration dependent on fatty acid oxidation, along with rewiring of the Krebs cycle through the activity of ATP citrate lyase. Together, these changes represented a hybrid of M1 and M2 metabolisms, and were critical for macrophage engulfment of PDAC cells and anti-tumor activity. Our findings indicate that immune activation of macrophages alter their metabolic state rather than their M1/M2 phenotype to enable them to overcome inhibitory CD47 and carry out anti-tumor activity

Metabolic Rewiring of Macrophages Promotes Anti-Tumor Activity in Pancreatic Cancer

Macrophages abound in the tumor microenvironment of pancreatic cancer and other solid malignancies. Although macrophages typically promote tumorigenesis, they also represent key targets for immunotherapy approaches, which aim to: 1) deplete macrophages, 2) inhibit their activity, or 3) redirect them toward an anti-tumor role. Redirecting macrophages is commonly described as a phenotypic shift from M2 (anti-inflammatory) to M1 (pro-inflammatory) polarization. However, macrophage phenotypes have grown increasingly diverse and only loosely describe functional roles. Here we examine the anti-tumor functions of macrophages – their ability to engulf and kill tumor cells – and the metabolic dependencies of this process, using a syngeneic and fully immunocompetent tumor model of pancreatic ductal adenocarcinoma (PDAC). In PDAC cells derived from KPC (KrasLSL.G12D/+; Trp53R172H/+; Pdx-Cre) mice, the anti-phagocytic receptor CD47 was knocked out using transient CRISPR-Cas9 expression. CD47 is overexpressed by tumor cells to suppress macrophage anti-tumor activity and escape cancer immunosurveillance. Despite the critical role of CD47, we found that complete loss of CD47 in PDAC cells did not induce macrophage engulfment in vitro , nor did it impact tumor growth in vivo. We hypothesized that macrophages required an activated state, and found that ODN1826, a CpG oligonucleotide, could stimulate macrophages to engulf tumor cells whether they expressed CD47 or not, and without inducing classical M1 or M2 markers. Moreover, CpG treatment of tumor-bearing mice induced potent anti-tumor responses that required macrophages, but not lymphocytes, natural killer cells, or dendritic cells. CpG activation was found to promote oxidative respiration dependent on fatty acid oxidation, along with rewiring of the Krebs cycle through the activity of ATP citrate lyase. Together, these changes represented a hybrid of M1 and M2 metabolisms, and were critical for macrophage engulfment of PDAC cells and anti-tumor activity. Our findings indicate that immune activation of macrophages alter their metabolic state rather than their M1/M2 phenotype to enable them to overcome inhibitory CD47 and carry out anti-tumor activity

A Review on Styrene Substitutes in Thermosets and Their Composites

In recent decades, tremendous interest and technological development have been poured into thermosets and their composites. The thermosets and composites with unsaturated double bonds curing system are especially concerned due to their versatility. To further exploit such resins, reactive diluents (RDs) with unsaturated sites are usually incorporated to improve their processability and mechanical properties. Traditional RD, styrene, is a toxic volatile organic compound and one of the anticipated carcinogens warned by the National Institute of Health, USA. Most efforts have been conducted on reducing the usage of styrene in the production of thermosets and their composites, while very few works have systematically summarized these literatures. Herein, recent developments regarding styrene substitutes in thermosets and their composites are reviewed. Potential styrene alternatives, such as vinyl derivatives of benzene and (methyl)acrylates are discussed in details. Emphasis is focused on the strategies on developing novel RD monomers through grafting unsaturated functional groups on renewable feedstocks such as carbohydrates, lignin, and fatty acids. This review also highlights the development and characteristics of RD monomers and their influence on processability and mechanical performance of the resulting thermosets and composites

Preparation and Performance of Cement Mortar Reinforced by Modified Bamboo Fibers

This study aims to prepare bamboo-fiber-reinforced cement composites and provide a solution to the issue of poor interfacial adhesion between bamboo fibers and cement matrix. The original bamboo fibers were modified by three moderately low-cost and easy-to-handle treatments including glycerol, aluminate ester, and silane treatments. The performance of the modified bamboo-fiber-reinforced cement composites was evaluated by a series of mechanical and durability tests, including flexural and compressive strength, water absorption, chloride ion penetration, drying shrinkage, freeze–thaw resistance, and carbonization. In addition, the microstructures of composites were characterized using a scanning electron microscope (SEM). The results showed that the composites reinforced with glycerol-modified bamboo fibers had 14% increased flexural strength and comparable compressive strength. From durability perspectives, all treatments showed similar performance in drying shrinkage, whereas aluminate ester treatment was the most effective in terms of impermeability, chloride resistance, freeze–thaw resistance, and carbonization. The results could provide insights to efficient and effective natural fiber treatment to enable better performance of natural-fiber-reinforced cement-based materials

Study on the Hydrogen Effect and Interface/Border Traps of a Depletion-Mode AlGaN/GaN High-Electron-Mobility Transistor with a SiN_x Gate Dielectric at Different Temperatures

In this study, the electrical characteristics of depletion-mode AlGaN/GaN high-electron-mobility transistors (HEMTs) with a SiNx gate dielectric were tested under hydrogen exposure conditions. The experimental results are as follows: (1) After hydrogen treatment at room temperature, the threshold voltage VTH of the original device was positively shifted from −16.98 V to −11.53 V, and the positive bias of threshold was 5.45 V. When the VDS was swept from 0 to 1 V with VGS of 0 V, the IDS was reduced by 25% from 9.45 A to 7.08 A. (2) Another group of original devices with identical electrical performance, after the same duration of hydrogen treatment at 100 °C, exhibited a reverse shift in threshold voltage with a negative threshold shift of −0.91 V. The output characteristics were enhanced, and the saturation leakage current was increased. (3) The C-V method and the low-frequency noise method were used to investigate the effect of hydrogen effect on the device interface trap and border trap, respectively. It was found that high-temperature hydrogen conditions can passivate the interface/border traps of SiNx/AlGaN, reducing the density of interface/border traps and mitigating the trap capture effect. However, in the room-temperature hydrogen experiment, the concentration of interface/border traps increased. The research findings in this paper provide valuable references for the design and application of depletion-mode AlGaN/GaN HEMT devices

Effects of Ban Lian Zi Jin San on intestinal inflammation and barrier function of heat-stressed broilers

ABSTRACT: Heat stress (HS) in broilers can be an environmental stressor that leads to intestinal inflammation and intestinal barrier damage. In order to examine the effect of Ban Lian Zi Jin San (BLZJS) on intestinal inflammation and barrier function in heat-stressed broilers, a model of chronic cyclic HS in broilers was established. A total of 300 twenty-one-day-old broilers were divided into 5 treatments at random. Broilers in 3 BLZJS dosage groups were kept in an ecologically controlled room at 37℃ ± 2℃ for 6 wk, and fed basal diets supplemented with 0.5, 1, and 2% BLZJS. Broilers in HS group were housed in the same room, but fed the basal diets. The findings indicated that supplementation of BLZJS significantly declined serum HS indexes levels (HSP70, HSP90), and increased serum antioxidant capacity (SOD and T-AOC) in broilers (P < 0.05). Besides, supplementation of BLZJS significantly inhibited the expression of HS indexes (HSP70 and HSP90), genes related to TLR4 inflammatory signal pathway (TLR4, MyD88, TRIF, IRAK-4, and NF-κB), inflammatory factors (IL-6 and TNF-α), and upregulated anti-inflammatory cytokines (IL-10) and intestinal tight junction-related genes (Occludin, Claudin-1, and ZO-1) in broiler jejunum (P < 0.05). On the other hand, supplementation of BLZJS could significantly reduce the protein expression of NF-κB and HSP70 in chick jejunum (P < 0.05). In conclusion, BLZJS inhibited the activation of TLR4 signal pathway and reduced the production of inflammatory factors, restoring the level of intestinal tight junction protein and protecting jejunal intestinal barrier function in heat-stressed broilers