Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade.

The efficacy and side effects of radiotherapy (RT) depend on parameters like dose and the volume of irradiated tissue. RT induces modulations of the tumor immune microenvironment (TIME) that are dependent on the dose. Low dose RT (LDRT, i.e., single doses of 0.5-2 Gy) has been shown to promote immune infiltration into the tumor. Here we hypothesize that partial tumor irradiation combining the immunostimulatory/non-lethal properties of LDRT with cell killing/shrinkage properties of high dose RT (HDRT) within the same tumor mass could enhance anti-tumor responses when combined with immunomodulators. In models of colorectal and breast cancer in immunocompetent female mice, partial irradiation (PI) with millimetric precision to deliver LDRT (2 Gy) and HDRT (16 Gy) within the same tumor induces substantial tumor control when combined with anti-PD1. Using flow cytometry, cytokine profiling and single-cell RNA sequencing, we identify a crosstalk between the TIME of the differentially irradiated tumor volumes. PI reshapes tumor-infiltrating CD8+ T cells into more cytotoxic and interferon-activated phenotypes but also increases the infiltration of pro-tumor neutrophils driven by CXCR2. The combination of the CXCR2 antagonist SB225002 with PD1 blockade and PI improves tumor control and mouse survival. Our results suggest a strategy to reduce RT toxicity and improve the therapeutic index of RT and immune checkpoint combinations.

Nonpersistent Nanoarchitectures Enhance Concurrent Chemoradiotherapy in an Immunocompetent Orthotopic Model of HPV+ Head/Neck Carcinoma.

Cisplatin chemoradiotherapy (CRT) is the established standard of care for managing locally advanced human papillomavirus-positive head/neck carcinoma. The typically young patients may suffer serious and long-time side effects caused by the treatment, such as dysphagia, and hearing loss. Thus, ensuring a satisfactory post-treatment quality of life is paramount. One potential replacing approach to the classical CRT involves the combination of standard-dose radiotherapy and radiosensitizers such as noble metal nanoparticles (NPs). However, several concerns about size, shape, and biocompatibility limit the translation of metal nanomaterials to the clinical practice. Here, it is demonstrated that a new model of nonpersistent gold nanoarchitectures containing cisplatin (NAs-Cluster-CisPt) generates, in combination with radiotherapy, a significant in vivo tumor-reducing effect compared to the standard CRT, achieving a complete tumor clearance in 25% of the immunocompetent models that persist for 60 days. These findings, together with the negligible amount of metals recognized in the excretory organs, highlight that the concurrent administration of NAs-Cluster-CisPt and radiotherapy has the potential to overcome some clinical limitations associated to NP-based approaches while enhancing the treatment outcome with respect to standard CRT. Overall, despite further mechanistic investigations being essential, these data support the exploiting of nonpersistent metal-nanomaterial-mediated approaches for oral cancer management.

Meta-Analysis of Herbicide Non-Target Effects on Pest Natural Enemies.

A critical component of integrated pest management is minimizing disruption of biological control by reducing the use of pesticides with significant non-target effects on natural enemies. Insecticide non-target effects testing for natural enemies has become increasingly common, but research examining the non-target effects of herbicides on natural enemies is scarce, and recommendations regarding herbicide selectivity are non-existent. We used meta-analysis to summarize laboratory bioassays testing non-target effects of herbicides on arthropod natural enemies and identify patterns in taxon susceptibility and active ingredient toxicity. Data were extracted from 78 papers representing 801 total observations. Herbicides increased natural enemy mortality and decreased longevity, reproduction, and predation. Mesostigmatan mites and hemipterans were the most sensitive to herbicides, and spiders, neuropterans, and hymenopterans were the least sensitive. Mortality was higher in juvenile predators versus parasitoids but did not differ between adults; parasitoid juveniles are likely better protected within the host. In terms of acute mortality, metribuzin, glufosinate, and oxyfluorfen were the most harmful herbicides. Only nicosulfuron, rimsulfuron, pendimethalin, phenmedipham, atrazine, and urea did not increase natural enemy mortality. The large effect size of glufosinate is particularly concerning, as it is the most likely replacement herbicide for glyphosate in many crops. Many active ingredients remain under-studied. Our analysis indicates that herbicides have a strong potential to disrupt biological control in cropping systems.

Herbicides Harm Key Orchard Predatory Mites.

The phytoseiid mites Galendromus occidentalis and Amblydromella caudiglans are critical for conservation biological control of pest mites in Washington State, U.S.A. apples. While the non-target effects of insecticides on phytoseiids are well described, research on herbicide effects is limited. Using laboratory bioassays, we examined lethal (female mortality) and sublethal (fecundity, egg hatch, larval survival) effects of seven herbicides and five adjuvants on A. caudiglans and G. occidentalis. The effects of mixing herbicides with recommended adjuvants were also tested to determine if the addition of an adjuvant increased herbicide toxicity. Glufosinate was the least selective herbicide tested, causing 100% mortality in both species. Paraquat caused 100% mortality in A. caudiglans and 56% mortality in G. occidentalis. Sublethal effects were significant for both species when exposed to oxyfluorfen. Adjuvants did not cause non-target effects in A. caudiglans. The non-ionic surfactant and methylated seed oil increased mortality and decreased reproduction in G. occidentalis. The high toxicity of glufosinate and paraquat for both predators is concerning; these are the primary "burn down" herbicide alternatives to glyphosate, which is decreasing in use due to consumer toxicity concerns. Field studies are needed to determine the extent to which herbicides disrupt orchard biological control, focusing on glufosinate, paraquat, and oxyfluorfen. Consumer preferences will need to be balanced with natural enemy conservation.

Updating integrated mite management 50 years later: comparing laboratory pesticide susceptibility of a 'new' generalist predatory mite to a cornerstone specialist predator.

BACKGROUND: Historically, integrated mite management in Washington apple orchards has focused on conservation of the predatory mite Galendromus occidentalis (Nesbitt) to reduce secondary pest mite pressure. However, pesticide use has changed to include more selective products, coinciding with a shift in the predatory mite community composition to include a new major predator, Amblydromella caudiglans (Schuster). There is evidence that A. caudiglans is more pesticide sensitive than G. occidentalis. Therefore, updates to pesticide selectivity recommendations are needed to conserve this 'new' key predator. Using bioassays, we examined the lethal (female mortality) and sublethal effects (fecundity, egg hatch, larval survival) of 4 fungicides and 11 insecticides on A. caudiglans, to determine whether existing conservation recommendations can be applied to this predatory mite. Susceptibility was compared with prior research on G. occidentalis. RESULTS: Mancozeb was the least selective fungicide tested on A. caudiglans; it caused high acute toxicity and sublethal effects. Carbaryl was the least selective insecticide and caused 100% mortality. Captan was the most selective fungicide. Chlorantraniliprole and cyantraniliprole were the most selective insecticides and therefore least likely to disrupt biological control by A. caudiglans. Non-target effects on A. caudiglans and G. occidentalis were similar, but A. caudiglans experienced higher mortality to some broad-spectrum insecticides. CONCLUSIONS: All the products tested had some non-target effects on A. caudiglans. However, A. caudiglans sensitivity to most tested pesticides was similar to that of G. occidentalis. In general, existing spray recommendations for conserving G. occidentalis can be adjusted slightly and applied to A. caudiglans conservation. © 2023 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Nontarget Impacts of Herbicides on Spiders in Orchards.

Spiders are key predators in many agroecosystems, including orchards. Despite the importance of spiders in biological control, pesticide nontarget effects on this group are poorly described. This is especially true for herbicides, which spiders frequently encounter as they move between the ground cover and tree canopy. We sought to determine the nontarget effects of seven herbicides used in orchards on three species of spiders that are commonly found in Washington state (USA) orchards: Pelegrina aeneola (Curtis) (Araneae: Salticidae), Philodromus cespitum (Walckenaer) (Araneae: Philodromidae), and Phanias watonus (Chamberlin & Ivie) (Araneae: Salticidae). Immature spiders were collected from orchards and used in laboratory assays. Single spiders were placed in vials with dried herbicide residues and mortality was evaluated after 1, 2, and 5 d. We also evaluated herbicide impacts on prey consumption rates and on spider movement using motion-tracking software. Only oxyfluorfen caused significant spider mortality. P. cespitum seemed to be less acutely sensitive to oxyfluorfen than the two salticid species. Several herbicide treatments significantly increased locomotion in P. cespitum, whereas rimsulfuron numerically decreased movement of P. aeneola. Sulfonylurea herbicides (rimsulfuron, halosulfuron) decreased prey consumption of P. aeneola. Our work indicates that although spiders may be less acutely sensitive to some pesticides than beneficial insects, they can be affected by sublethal effects of herbicides. Future work should determine if herbicide applications impact spider abundance in the field and reduce biological control services. In general, more work is needed on the impacts of herbicides on natural enemies.

Spider mite resistance to miticides in South Carolina strawberry and implications for improved integrated pest management.

Tetranychus urticae Koch (Acari: Tetranychidae), twospotted spider mite, is a major secondary pest of strawberry and can cause significant yield loss. Tetranychus urticae is typically controlled using miticides, which has led to rapid resistance development. In South Carolina (USA), extension agents and growers have reported field failures of miticides (inadequate pest suppression), but resistance has not been quantitatively determined. In 2018, we determined the level of miticide resistance of six T. urticae populations found on strawberry across South Carolina. We examined efficacy of all miticides registered for use on US strawberry by conducting an initial diagnostic bioassay at 20% of the maximum labeled field rate. Any population × active ingredient combination resulting in < 55% mortality was identified as 'potentially resistant' and concentration-response bioassays were then conducted to calculate LC50 values for an individual population. These values were compared with those of a known-susceptible laboratory population to calculate resistance ratios (RR). Our results indicate that examined South Carolina populations of T. urticae from strawberry were highly resistant to bifenthrin (RR = 100-60,000) and there was reduced susceptibility to fenbutatin-oxide (RR = 25-123). The 'Sardinia' population had decreased abamectin susceptibility (RR = 25). No resistance to hexythiazox, etoxazole, acequinocyl, bifenazate, fenpyroximate, spiromesifen, or cyflumetofen was found. Based on available data, it appears that miticide resistance is not a likely cause of field failures and issues related to application error and coverage should be investigated. Overall, this work supports the need to reduce the use of broad-spectrum pesticides and older products, in favor of newer miticide chemistries due to resistance issues.

Characterizing college science instruction: The Three-Dimensional Learning Observation Protocol.

The importance of improving STEM education is of perennial interest, and to this end, the education community needs ways to characterize transformation efforts. Three-dimensional learning (3DL) is one such approach to transformation, in which core ideas of the discipline, scientific practices, and crosscutting concepts are combined to support student development of disciplinary expertise. We have previously reported on an approach to the characterization of assessments, the Three-Dimensional Learning Assessment Protocol (3D-LAP), that can be used to identify whether assessments have the potential to engage students in 3DL. Here we present the development of a companion, the Three-Dimensional Learning Observation Protocol (3D-LOP), an observation protocol that can reliably distinguish between instruction that has potential for engagement with 3DL and instruction that does not. The 3D-LOP goes beyond other observation protocols, because it is intended not only to characterize the pedagogical approaches being used in the instructional environment, but also to identify whether students are being asked to engage with scientific practices, core ideas, and crosscutting concepts. We demonstrate herein that the 3D-LOP can be used reliably to code for the presence of 3DL; further, we present data that show the utility of the 3D-LOP in differentiating between instruction that has the potential to promote 3DL from instruction that does not. Our team plans to continue using this protocol to evaluate outcomes of instructional transformation projects. We also propose that the 3D-LOP can be used to support practitioners in developing curricular materials and selecting instructional strategies to promote engagement in three-dimensional instruction.

Not all predators are equal: miticide non-target effects and differential selectivity.

BACKGROUND: Biological control in conventional agroecosystems involves the integration of chemical and conservation tactics, requiring knowledge of pesticide non-target effects on key natural enemies. Even for natural enemy groups such as predatory mites (Acari: Phytoseiidae), where pesticide non-target effects have been thoroughly examined, there may be significant differences in species susceptibility to specific active ingredients, including newer selective products. Using bioassays, we examined lethal (female mortality) and sublethal (fecundity, egg hatch, larval survival) effects of ten miticides on a spider mite pest (Tetranychus urticae) and three insectary-purchased predatory mites (Phytoseiulus persimilis, Neoseiulus californicus, and N. fallacis) commonly used for its management. Susceptibility of field-collected and insectary-reared populations of P. persimilis was also compared. Cumulative impacts on production of larvae by treated female spider mites and predators were compared to create a metric that simultaneously accounted for miticide efficacy and selectivity. RESULTS: Bifenthrin was the least selective, as it caused acute toxicity to all predators and had little efficacy against T. urticae. Hexythiazox and cyflumetofen were the most selectively favorable. Phytoseiulus persimilis populations were similar in which miticides they were sensitive to, although the insectary-purchased population was generally more sensitive. CONCLUSIONS: All products, including those considered selective (cyflumetofen, bifenazate, acequinocyl) had non-target effects on at least one species of predator tested. This work emphasizes that there is high variability in selectivity among species, highlighting the need to examine key natural enemies individually when creating management programs. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.