Antitumor Effects of Vitamin D Analogs on Hamster and Mouse Melanoma Cell Lines in Relation to Melanin Pigmentation

Deregulated melanogenesis is involved in melanomagenesis and melanoma progression and resistance to therapy. Vitamin D analogs have anti-melanoma activity. While the hypercalcaemic effect of the active form of Vitamin D (1,25(OH)₂D₃) limits its therapeutic use, novel Vitamin D analogs with a modified side chain demonstrate low calcaemic activity. We therefore examined the effect of secosteroidal analogs, both classic (1,25(OH)₂D₃ and 25(OH)D₃), and novel relatively non-calcemic ones (20(OH)D₃, calcipotriol, 21(OH)pD, pD and 20(OH)pL), on proliferation, colony formation in monolayer and soft-agar, and mRNA and protein expression by melanoma cells. Murine B16-F10 and hamster Bomirski Ab cell lines were shown to be effective models to study how melanogenesis affects anti-melanoma treatment. Novel Vitamin D analogs with a short side-chain and lumisterol-like 20(OH)pL efficiently inhibited rodent melanoma growth. Moderate pigmentation sensitized rodent melanoma cells towards Vitamin D analogs, and altered expression of key genes involved in Vitamin D signaling, which was opposite to the effect on heavily pigmented cells. Interestingly, melanogenesis inhibited ligand-induced Vitamin D receptor translocation and ligand-induced expression of VDR and CYP24A1 genes. These findings indicate that melanogenesis can affect the anti-melanoma activity of Vitamin D analogs in a complex manner.     

Mixed-Metal MOF-74 Templated Catalysts for Efficient Carbon Dioxide Capture and Methanation

The vast chemical and structural tunability of metal–organic frameworks (MOFs) are beginning to be harnessed as functional supports for catalytic nanoparticles spanning a range of applications. However, a lack of straightforward methods for producing nanoparticle-encapsulated MOFs as efficient heterogeneous catalysts limits their usage. Herein, a mixed-metal MOF, NiMg-MOF-74, is utilized as a template to disperse small Ni nanoclusters throughout the parent MOF. By exploiting the difference in Ni O and Mg O coordination bond strength, Ni²⁺ is selectively reduced to form highly dispersed Ni nanoclusters constrained by the parent MOF pore diameter, while Mg²⁺ remains coordinated in the framework. By varying the ratio of Ni to Mg in the parent MOF, accessible surface area and crystallinity can be tuned upon thermal treatment, influencing CO₂ adsorption capacity and hydrogenation selectivity. The resulting Ni nanoclusters prove to be an active catalyst for CO₂ methanation and are examined using extended X-ray absorption fine structure and X-ray photoelectron spectroscopy. By preserving a segment of the Mg²⁺-containing MOF framework, the composite system retains a portion of its CO₂ adsorption capacity while continuing to deliver catalytic activity. The approach is thus critical for designing materials that can bridge the gap between carbon capture and CO₂ utilization.     

Quantifying the limits of CAR T-cell delivery in mice and men

CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10–100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.     

Liquid phase sintering and characterization of SiC ceramics

The present study focuses on the sintering of silicon carbide-based ceramics (SiC) by liquid phase sintering (LPS) followed by characterization of the produced ceramics. AlN/Re₂O₃ mixtures were used as additives in the LPS process. In the first step, the LPS-SiC materials were produced in a graphite resistance furnace in the form of discs at different temperatures. The conditions with the best results regarding real density and relative density were taken as reference for sintering in the form of prismatic bars. In the second step, these samples were evaluated regarding fracture toughness (K_IC), by the Single Edge V Notch Beam – SEVNB – method, and flexural strength. K_IC behavior was evaluated according to the depth and curvature radius of the notches. Reliable K_IC values were presented when the ceramic displayed a small curvature radius at the notch tip. When the radius was large, it did not maintain the square root singularity of the notch tip. Tests were carried out to determine K_IC values in atmospheric air and water. K_IC results were lower in water than air, with a decrease ranging between 2.56% and 11.26%. The observations indicated a direct grain size correlation between K_IC values and fracture strength of the SiC ceramics.     

A Constitutive Equation of Thermoelasticity for Solid Materials

A new constitutive equation of thermoelasticity for crystals is presented based on the interatomic potential and solid mechanics at finite temperature. Using the new constitutive equation, the calculations for crystal copper and graphene are carried out under different loading paths at different temperatures. The calculated results are in good agreement with those of the previous thermoelasticity constitutive equation based on quantum mechanics, which clearly indicates that our new constitutive equation of thermoelasticity is correct. A lot of comparisons also show that the present theory is more concise and efficient than the previous thermal stress theory in the practical application.     

Nutrient digestibility and endogenous protein losses in the foregut and small intestine of weaned dairy calves fed calf starters with conventional or enzyme-treated soybean meal

The aims of this experiment were (1) to compare the effects of a soybean meal with an enzymatic treatment (ESBM) to reduce the concentration of antinutritional factors versus a standard soybean meal (SBM) on foregut and small intestine digestion in weaned dairy calves and (2) to estimate the endogenous losses of crude protein (CP) in the small intestine. Our hypothesis was that a diet containing ESBM instead of SBM would improve ruminal and small intestine digestion and absorption of nutrients. A T-cannula was placed in the duodenum, and a second T-cannula was installed in the distal ileum of 12 Holstein calves at approximately 3 wk of age. Calves were weaned on d 42, and on d 50 they were assigned randomly to a quadruplicated 3 × 3 Latin square with 10-d periods. Digesta samples were collected on d 7 and 8 from the ileum and d 9 and 10 from the duodenum. The diets were fed for ad libitum intake and consisted of a calf starter (CS) of 20% CP with SBM as the main source of protein (CTRL), and an isonitrogenous CS with an ESBM instead of SBM (ENZT). A third diet with a low content of CP (10%) and no soy protein was fed to estimate endogenous N losses and digestibilities of test ingredients. Flows and digestibilities of nutrients were compared between CTRL and ENZT and their test ingredients (SBM vs. ESBM, respectively). Duodenal net flows of CP and total AA as well as ruminal microbial protein synthesis per kilogram of digested CP were greater, and flow of nonprotein N and CP true (corrected by endogenous and microbial flows) foregut digestibility were lower with ENZT than CTRL. The apparent small intestine digestibilities of CP and total AA were greater for ESBM than SBM, but there were no differences between the CTRL and ENZT diets. We observed no differences in digestibilities at the duodenum or ileum of starch or NDF, but true small intestine digestibilities of CP and all AA were greater with ENZT than CTRL. Total endogenous protein losses in the small intestine estimated from calves fed the low-CP with no soy protein diet were 37 ± 1.5 g of CP and 29 ± 1.4 g of AA/kg of DMI. These values may be considered the basal endogenous losses as they are similar to values obtained with the regression method, which estimates N losses when dietary N is null. Our results indicated that the inclusion of an ESBM improved the efficiency of ruminal microbial protein synthesis per digested kilogram of organic matter and CP, and increased CP and AA absorption in the small intestine despite a greater proportion of undigested dietary protein entering the duodenum.