Pharmacological inhibition of β-catenin/BCL9 interaction modulates T
reg
cells and improves immunotherapy.
The Wnt/β-catenin (β-cat) pathway plays a critical role in cancer. Using hydrocarbon-stapled ...peptide technologies, we aim to develop potent, selective inhibitors targeting this pathway by disrupting the interaction of β-cat with its coactivators B-cell lymphoma 9 (BCL9) and B-cell lymphoma 9-like (B9L). We identified a set of peptides, including hsBCL9
CT
-24, that robustly inhibits the activity of β-cat and suppresses cancer cell growth. In animal models, these peptides exhibit potent anti-tumor effects, favorable pharmacokinetic profiles, and minimal toxicities. Markedly, these peptides promote intratumoral infiltration of cytotoxic T cells by reducing regulatory T cells (T
reg
) and increasing dendritic cells (DCs), therefore sensitizing cancer cells to PD-1 inhibitors. Given the strong correlation between T
reg
infiltration and
APC
mutation in colorectal cancers, it indicates our peptides can reactivate anti-cancer immune response suppressed by the oncogenic Wnt pathway. In summary, we report a promising strategy for cancer therapy by pharmacological inhibition of the Wnt/β-cat signaling.
Plant polyphenols, especially flavonoids, are of great interest due to their wide range of biological activities. Quercetin, a ubiquitous flavonoid, is known to have antioxidant and antibacterial ...effects. In this study, we investigated the effect of quercetin on performance, egg quality, cecal microflora populations, and antioxidant status in laying hens. Two hundred forty 28-wk-old Hessian laying hens, with an average laying rate of lay 85% at the start, were randomly allotted to 4 treatments and fed 1 of 4 diets (negative control, 0.2, 0.4, and 0.6 g of quercetin/kg of diet) for 8 wk. Layer performance responses, egg quality parameters, cecal microflora populations and antioxidant status were measured at the end of the experiment. Results showed that feed conversion decreased as the quercetin level increased. Laying rate had a quadratic correlation with the level of quercetin (P = 0.056) and was maximized by the supplementation level of 0.2 g/kg of diet. However, no significant quercetin effect was observed on egg quality. Regression analysis showed that the population of total aerobes and coliforms decreased and the population of Bifidobacteria increased as the level of quercetin increased. Regression analysis also showed the activities of Cu-Zn-superoxide dismutase increased as the level of quercetin increased (P < 0.05). Results of the study suggest that the appropriate level of supplementation is 0.367 to 0.369 g of quercetin/kg of feed based on the improvement of laying rate (with 88.55 as maximum value) and feed conversion (with 2.0725 as minimum value). Our observations provided further evidence that dietary supplementation of quercetin improved performance by modulation of intestinal environment and liver superoxide dismutase content in laying hens. Quercetin has the potential as functional feed additive in animal production.
1. At the end of the peak laying period for fowl, both performance and egg quality decrease markedly. Counteracting either or both of these could, therefore, have significant positive economic ...implications. Quercetin, a typical representative of the flavonol compounds, has a variety of biological functions. However, there are no reported findings on its use as a feed additive.2. In this study, we investigated the effects of quercetin on laying rate, egg quality and blood traits associated with egg quality in laying hens (Hessain) during the late laying period and explored the possibility of using quercetin as a functional feed additive.3. The laying hens (n = 240; 39 weeks old) were randomly assigned to 4 treatments consisting of 6 replicates (n = 10) and were fed with diets containing quercetin at 0, 0.2, 0.4 or 0.6 g/kg.4. Results showed that laying rate was increased and feed–egg ratio was decreased significantly by 0.2 and 0.4 g/kg quercetin. Compared with controls, Haugh unit, eggshell strength, eggshell thickness and yolk protein were increased, but yolk cholesterol was decreased by quercetin.5. In conclusion, quercetin was beneficial in improving performance and egg quality. The recommended concentration of quercetin is 0.4 g/kg of the basal diet. At this concentration, increased laying rate, improved egg quality and reduced yolk cholesterol can be expected.
► Weldments were done with laser shock processing impacts after cavitation erosion. ► Laser shock processing enhanced the erosion and corrosion resistance of weldments. ► Tensile residual stress and ...surface roughness decreased by laser shock processing. ► Microstructure was observed to explain the improvement by laser shock processing. ► Obvious passivation areas occurred with laser shock processing impacts.
Effects of laser shock processing (LSP) on electrochemical corrosion resistance of weldments after cavitation erosion were investigated by X-ray diffraction (XRD) technology, scanning electron microscope (SEM), roughness tester and optical microscope (OM). Some main factors to influence erosion and corrosion of weldments, residual stresses, surface roughness, grain refinements and slip, were discussed in detail. Results show that LSP impacts can induce compressive residual stresses, decrease surface roughness, refine grains and generate the slip. Thus, the erosion and corrosion resistance with LSP impacts is improved.
Rubia plants are one of the most important plant resources possessing significant commercial and medicinal values. Plant endophytes could benefit their host plants in different ways. Rubiaceae‐type ...cyclopeptides (RAs), mainly isolated from Rubia plants, have attracted considerable attentions for their distinctive bicyclic structures and significant antitumor activities, but their contents in plants are low. The aim of this study is to investigate the diversity of endophytic fungi in Rubia plants and their potential for production of RAs. In this work, 143 endophytic fungi isolates were obtained from two Rubia plants. Phylogenetic analysis was performed based on the ITS rDNA sequences, and the isolates were classified into 29 genera. Among them, four endophytic fungal strains were found to produce anti‐tumour RAs by LC‐MS/MS analysis. This work successfully provides valuable knowledges of endophytic fungi microbiome in Rubia plants for agricultural and industrial applications, and exploits a new environmental‐friendly resource of RAs.
Significance and Impact of the Study: In this work, 143 endophytic fungi isolates belonging to 29 genera were obtained from two Rubia plants. Among them, four endophytic fungal strains were found to produce anti‐tumour Rubiaceae‐type cyclopeptides, which were main anti‐tumour ingredients of Rubia plants. This is the first study on the systematic isolation of endophytic fungi from Rubia plants, and we believe that our work could provide valuable knowledges of endophytic fungi microbiome in Rubia plants for agricultural and industrial applications. Furthermore, our work could also exploit a new environmental‐friendly resource of Rubiaceae‐type cyclopeptides, which will avoid wildcrafting and overcollection of Rubia plants for environment protection.
•Second precipitation occurred when heat treated at 500°C.•Carbon-enriched stabilized austenite formed after tempering at 500°C.•Tempered sorbite formed after heat treated at 800°C.•FWHM decreases by ...45.5–65% after heat treatment at 800°C.•Lubricant greatly improves the wear resistance of specimen C.
M3:2 high-speed steel (HSS) coating was fabricated on one austenitic stainless steel by laser cladding (LC). The cladded specimen (specimen A) was heat treated at 500°C (specimen B) and 800°C (specimen C). Microstructure, phase structure, residual stress, micro-hardness and wear behavior of the specimens were examined. Dry sliding wear was carried out on each specimen and lubricant sliding wear (emulsifier solution and water served as lubricant) was carried out on specimen C. Results show that the observed microstructure of specimen A is characterized by comparably fine equiaxial grains, dendrites and inter-dendritic network shaped eutectic carbides. This microstructure is composed of supersaturated martensite, retained austenite and MxCy type carbides. Heat treatment, carried out on specimens B and C, leads to the relief of residual stress and phase transformation. Retained austenite enriches and stabilizes in specimen B. Tempered sorbite forms in specimen C. Both specimens show the existence of Fe2O3. Residual stress changes from tensile to compressive stress after heat treatment. The maximum principal stress change rates of specimens B and C compared with that of specimen A are −1.04 and −2.53, respectively. Average micro-hardness of specimen A increases by 4.3% and decreases by 32.5% after heat treated at 500°C and 800°C, respectively. Dry sliding wear resistance shows similar variation tendency with the microhardness of the HSS coating. Wear resistance of specimen B is the best during the dry sliding wear, and that of specimen C is the worst. Addition of lubricant greatly improves the wear resistance of specimen C.
The preceding works introduced the leapfrog complying divergence implicit finite-difference time-domain (CDI-FDTD) method, which exhibits high accuracy and unconditional stability. In this study, the ...method is reformulated to simulate general electrically anisotropic and dispersive media. The auxiliary differential equation (ADE) method is employed to solve the equivalent polarization currents, which are then integrated into the CDI-FDTD method. The iterative formulae are presented, and the calculation method is similar to that of the traditional CDI-FDTD method. Additionally, the Von Neumann method is utilized to analyze the unconditional stability of the proposed method. To evaluate the performance of the proposed method, three numerical cases are conducted. These include calculating the transmission and reflection coefficients of a monolayer graphene sheet and a monolayer magnetized plasma, as well as the scattering properties of a cubic block plasma. The numerical results obtained by the proposed method demonstrate its accuracy and efficiency in simulating general anisotropic dispersive media, compared to both the analytical method and the traditional FDTD method.
Streptococcus agalactiae has become one of the most important emerging pathogens in the aquaculture industry and has resulted in large economic losses for tilapia farms in China. In this study, three ...pairs of specific primers were designed and tested for their specificities and sensitivities in quantitative real‐time polymerase chain reactions (qPCRs) after optimization of the annealing temperature. The primer pair IGS‐s/IGS‐a, which targets the 16S‐23S rRNA intergenic spacer region, was finally chosen, having a detection limit of 8.6 copies of S. agalactiae DNA in a 20 μL reaction mixture. Bacterial tissue tropism was demonstrated by qPCR in Oreochromis niloticus 5 days post‐injection with a virulent S. agalactiae strain. Bacterial loads were detected at the highest level in brain, followed by moderately high levels in kidney, heart, spleen, intestines, and eye. Significantly lower bacterial loads were observed in muscle, gill and liver. In addition, significantly lower bacterial loads were observed in the brain of convalescent O. niloticus 14 days post‐injection with several different S. agalactiae strains. The qPCR for the detection of S. agalactiae developed in this study provides a quantitative tool for investigating bacterial tissue tropism in infected fish, as well as for monitoring bacterial colonization in convalescent fish.
In this paper, magnetically tunable random lasing from a polymer dispersed liquid crystal (PDLC) in a capillary was achieved by means of doping with magnetic nanoparticles (MNPs). We experimentally ...explored the effects of the concentration of MNPs and the amplitude and direction of the magnetic field on the emission properties of random lasing, such as threshold, envelope of the emission spectrum, and intensities. The related mechanism was also investigated theoretically. Experimental results also showed that weakly tuned effects appeared from the sample with a polymer or pure liquid crystal (LC) doped with MNPs in comparison with PDLCs. Our research would provide an additional way to achieve tunable compact LC-based lasers.
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