Oncolytic viruses (OVs) are promising tumor-selective treatments, and the efficacy of OV therapies has been shown to depend heavily on the successful delivery and spread of these agents within the tumor mass to generate profound immunostimulatory effects. We have previously reported the potential of vanadium-based compounds such as vanadyl sulfate (VS) as immune-stimulatory enhancers of OV immunotherapy. These compounds, in conjunction with RNA-based OVs such as oncolytic VSVΔ51, improve viral spread and oncolysis, leading to long-term antitumor immunity and prolonged survival in resistant tumor models as previously reported. This effect is associated with a virus-induced antiviral type I IFN response shifting towards a type II IFN response. Here, the systemic impact and the relevant immunological changes following VS/VSVΔ51 combination therapy were investigated to understand the immunological mechanism of action leading to improved antitumor responses. We screened for the secretion of chemokines and cytokines in vivo to understand the mechanism of action regulating the recruitment of immune cells to the tumor in the CT26WT tumor model following treatment. Additionally, the antigen-specific immune response was investigated to further identify the relevant immunological changes following treatment with the VS+VSVΔ51 combination. Our data revealed that VS+VSVΔ51 combination therapy significantly increased the levels of IFN-γ and IL-6, and other key important pro-inflammatory cytokines and chemokines. Improved tumor antigen-specific T-cell responses were observed following the combined therapy. Supported by relevant immunological changes and as a proof of concept for the design of more effective therapeutic regimens, we found that local delivery of VSVΔ51 encoded with IL-12 or with other transgenes in combination with VS further improved therapeutic outcomes in a syngeneic CT26WT colon cancer model. We found that CD8+ T cells and Natural Killer (NK) cells play significant roles in establishing the therapeutic efficacy that we observed; Furthermore, engineering new and targeted therapeutic platforms to impact the antitumor immune response further improves the therapeutic benefits of the combined therapy.

A fish kill was observed in a historically freshwater region of the Everglades, coinciding with a spike in salinity. Sea level rise and altered hydrology allow freshwater wetland systems to be susceptible to saltwater intrusion. Most wetlands are characterized by highly organic soils with microbial communities starved of oxygen, seeking alternative electron acceptors. Seawater contains sulfate (SO42-), which is one of the alternative electron acceptors. Provided with sufficient quantities, sulfate-reducing bacteria (SRB) outcompete other anaerobes and produce toxic hydrogen sulfide. This study asked, what combination of soil organic matter (SOM) and SO42- are needed to produce sulfide concentrations potentially lethal to freshwater fish? Soil samples were collected from two freshwater wetlands with varying SOM content and incubated in microcosms at four SO42- concentrations (0, 0.75, 4.0, and 12.0 mM Na2SO4). Sulfide concentrations produced were compared to published data on lethal sulfide toxicity levels for aquatic life. This study demonstrated that high SOM soils (89.3 ± 0.2 % moisture) incubated with SO42- concentrations > 0.75 mM, rapidly produced toxic sulfide concentrations (> 5 ppm S2-) within 24 hrs.. While many freshwater species may tolerate a salinity of 1 ppt (0.75 mM SO42-), this SO42-concentration is sufficient to support SRB and lead to toxic sulfide production. ese results support the need to restore freshwater hydrology in wetland systems, such as the Everglades, thereby protecting against the rapid ecological effects of saltwater intrusion.

Homogeneity of powder blends is an important metric for industrial applications in fortified dairy foods including commercial pediatric nutrition products. Product development practices evaluating physical properties and nutrient stability performance are reliant on blending parameters that deliver a uniform powder at both the pilot and commercial scale. Quantities of individual micronutrients in finished products are particularly critical for formulated infant foods. The two preliminary phases of this study focused on developing a simple, efficient method, specifically for a pilot scale ribbon blender, in which maximum homogeneity in fortified dairy-based powder blends could be reached. In phase one, a red iron oxide pigment powder was mixed throughout a white dairy powder and color homogeneity was measured by comparing L*a*b* color values from powder samples extracted from different areas of the ribbon blender. For phase two, sixteen similar fortified dairy blends were produced with varying ribbon blade shaft rpm, fill level, and blending durations according to a response surface method (RSM). The level of homogeneity of ferrous sulfate in the dairy blend was measured in these fortified mixtures to determine optimal blender parameters. After operating parameters were determined for uniform blending, phase three was enacted using these parameters. A comparison study of nutrient stability in fortified model non-agglomerated powder infant formula (PIF) and agglomerated whey protein concentrate (WPC) powder blends was executed to evaluate the degradative effect of microencapsulated ferrous sulfate (MFS) vs. unencapsulated ferrous sulfate (UFS) in these fortified dairy blends. The nutrient degradation rates of vitamins A, E and C in both PIF and WPC base powder, fortified with either MFS or UFS, were determined and compared during an accelerated eight-week stability study. Using p = 0.05, no statistically significant differences in vitamin degradation rates were observed when comparing independent spray-dried dairy-based blends containing unencapsulated or microencapsulated ferrous sulfate (using an encapsulating composition of 60% stearic acid) during eight weeks of accelerated shelf-life storage conditions (37 °C with a 75% relative humidity, RH). Of note, the degradation rates of vitamins A and E in blends containing PIF and UFS were more rapid than the control and suggestively significantly different (p = 0.07).

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