Similar Effects Research Articles

Attention Modulates Human Visual Responses to Objects by Tuning Sharpening.

Visual stimuli compete with each other for cortical processing and attention biases this competition in favor of the attended stimulus. How does the relationship between the stimuli affect the strength of this attentional bias? Here, we used functional MRI to explore the effect of target-distractor similarity in neural representation on attentional modulation in the human visual cortex using univariate and multivariate pattern analyses. Using stimuli from four object categories (human bodies, cats, cars and houses), we investigated attentional effects in the primary visual area V1, the object-selective regions LO and pFs, the body-selective region EBA, and the scene-selective region PPA. We demonstrated that the strength of the attentional bias towards the target is not fixed but decreases with increasing target-distractor similarity. Simulations provided evidence that this result pattern is explained by tuning sharpening rather than an increase in gain. Our findings provide a mechanistic explanation for behavioral effects of target-distractor similarity on attentional biases and suggest tuning sharpening as the underlying mechanism in object-based attention.

Evaluation of Hydrazide-hydrazone and 4-thiazolidinone Derivatives of Etodolac as Potential Anticancer Agents in Leukemia Cells

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used for their anti-inflammatory and analgesic properties, have also been found to prevent cancer. (±)(R,S) Etodolac is an NSAID that belongs to the class of cyclooxygenase-2 inhibitors. Various derivatives of etodolac are synthesized to boost its anti-proliferative action and lessen its potential negative effects. In our earlier studies, some novel derivatives of etodolac exhibited stronger cytotoxic effects on prostate cell lines and had similar effects on leukemia cells in pre-screening experiments. Objective: Using the K562 leukemia cell line as a model, we sought to investigate the anti-cancer properties of a hydrazide-hydrozone derivative (SGK-205) and a 4-thiazolidinone derivative of etodolac (SGK-216). Materials and Methods: In the current investigation, SGK-205 and SGK-216 compounds were administered to K562 cells for 24 and 48 hours at concentrations of 10, 25, 50, 75 and 100 μM. Cell viability was assessed using the MTT test, and apoptosis by Annexin V-PI staining and mitochondrial membrane potential assays, together with mRNA expressions of apoptotic proteins. The levels of the proteins, HER2 and COX2, were also examined to evaluate COX2 inhibitory capacity. Results: In K562 cells, there was a definite dose-dependent response to SGK-205 and SGK-216 compounds. Results from MTT viability tests, together with mitochondrial membrane potential measurements and Annexin V-PI staining, revealed that SGK-216 and SGK-205 significantly outperformed etodolac in terms of their apoptotic and anti-proliferative activities. The concentration range of 10-20 M for both chemicals was sufficient to start biological responses. Apoptosis was also investigated through the expressions of pro- and anti-apoptotic proteins. Additionally, gene expression research demonstrated SGK-205 to be a beneficial substitute to etodolac in lowering COX-2 and human epidermal growth factor receptor-2 (HER2) expression. Conclusion: Our data indicated both derivatives to have higher anti-proliferative and apoptotic effects compared to etodolac. An overall assessment highlighting apoptotic induction potential, acceptable toxicity levels, a consistent dose-response relationship, and COX2 inhibitory actions, in particular, indicated SGK-205 as a viable novel therapeutic.

Higher Education and Local Educational Attainment: Evidence from the Establishment of U.S. Colleges

Abstract We investigate how the presence of a college affects local educational attainment. As counterfactuals for current college locations, we use historical “runner-up” locations that were strongly considered to become college sites but were ultimately not chosen. We find that winning counties today have college degree attainment rates 56% higher than runner-up counties and more private-sector employment in human-capital-intensive industries. These effects are not driven primarily by recent in-migration of educated adults, and alternative public investments did not have similar effects on local educational attainment. The results indicate that colleges played an important role in shaping long-run local outcomes.

Aerodynamic Performance of a Hovering Cycloidal Rotor: A CFD Study with Experimental Validation

A three‐dimensional (3D) unsteady Reynolds averaged Navier‐Stokes (URANS) computational fluid dynamics (CFD) toolkit for cycloidal rotors was developed and used to perform a parametric study. It included blade aspect ratio, side disks, pitch mechanism, blade camber, and shaft size. The influence of the pitch rod length showed the importance of the lift distribution between the upstream and downstream parts of the rotor cylinder. The application of blade camber significantly affected thrust and power, while having a limited effect on efficiency. A similar effect was obtained by varying the pitch rod lengths. The presence of a central axis in the rotor had a negligible effect on efficiency. The most significant impact on efficiency came from the side disks, which behaved similarly to winglets on fixed‐wing aircraft. However, changing the aspect ratio of the blades showed a similar response to that of aircraft wings, but with a smaller effect, making it conceivable to fly a square-bladed cyclorotor without side disks. To verify the CFD model, a cycloidal rotor was also built using 3D printed parts and carbon fiber tubing. It was then operated on a test rig where thrust and power were measured for speeds ranging from 408 to 2528 RPM. On the test bench, the blades were pitched with a uniform asymmetric mechanism. The maximum nose‐up pitch angle in upstream of the rotor axis was 34.8°. Due to its rotation around the rotor and its pitching in the opposite direction, the maximum nose‐up pitch angle of the downstream blade was 38.6°. The obtained rotor thrust and power curves and the flow visualization around the rotor confirmed the validity of the CFD toolkit.

Pip5k1γ regulates axon formation by limiting Rap1 activity.

During their differentiation, neurons establish a highly polarized morphology by forming axons and dendrites. Cortical and hippocampal neurons initially extend several short neurites that all have the potential to become an axon. One of these neurites is then selected as the axon by a combination of positive and negative feedback signals that promote axon formation and prevent the remaining neurites from developing into axons. Here, we show that Pip5k1γ is required for the formation of a single axon as a negative feedback signal that regulates C3G and Rap1 through the generation of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). Impairing the function of Pip5k1γ results in a hyper-activation of the Fyn/C3G/Rap1 pathway, which induces the formation of supernumerary axons. Application of a hyper-osmotic shock to modulate membrane tension has a similar effect, increasing Rap1 activity and inducing the formation of supernumerary axons. In both cases, the induction of supernumerary axons can be reverted by expressing constitutively active Pip5k. Our results show that PI(4,5)P2-dependent membrane properties limit the activity of C3G and Rap1 to ensure the extension of a single axon.

Doxing, political affiliation, and type of information: Effects on suspicion, perceived similarity, and hiring-related judgments.

Researchers have begun to focus on the influence of political affiliation in organizations. In this context, we investigated how doxing (i.e., using social media to post information online with malintent) influences hiring-related decisions. Based on the integration of a political affiliation and state suspicion model, we investigated how a dox containing different types of information (affirming a political party affiliation vs. providing derogatory/negative information about an opposing party) and political party affiliation similarity influenced hiring-related perceptions of job applicants. Given doxing's characteristics, we expanded the "decision space" to include effects about expected organizational image and expected retaliation. In Study 1, we found that the type of information and party similarity influenced suspicion of the applicant and perceived similarity with the applicant, whereas doxing only influenced suspicion. In turn, suspicion and perceived similarity predicted expected task performance and organizational image, and exploratory analyses suggested an interactive effect of these variables. Suspicion also predicted expected retaliation from individuals outside the organization. In Study 2, we confirmed that doxing was related to suspicion as well as the interactive effect of information type and party similarity. We explain that interaction using the notion of symbolic threat. In both studies, the effects of type of information and party similarity were pervasive. Our results support the similarity-attraction paradigm and a model of political affiliation. Expanding relevant theories to include suspicion helps better understand politically related judgments and the additional outcomes of expected organizational image and retaliation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

USP3 inhibition is Active Against Chemo-resistant Hepatocellular Carcinoma Anchorage-independent Growth via Suppressing Wnt/β-catenin.

USPs are a family of enzymes that regulate protein degradation, and their dysregulation has been implicated in the development and progression of cancer. This study aimed to determine whether ubiquitin-specific proteases 3 (USP3) could be a potential target for therapy in hepatocellular carcinoma (HCC), particularly in resistant HCC. This study systematically investigated the role of USP3 in HCC, with a focus on chemo-resistant HCC cells. The level of USP3 from clinical samples was measured using an ELISA assay. Cell proliferation, apoptosis, migration, and anchorage-independent colony formation assays were performed. Transfection was performed to knock down USP3 expression and measure β-catenin activity, and real-time PCR was used to measure levels of MYC and CYCLIN D1 genes. USP3 protein was upregulated in HCC tissues, but its upregulation was not associated with clinicopathology. USP3 knockdown had a similar inhibitory effect on growth in both sensitive and resistant HCC cells, did not affect migration, and induced apoptosis in sensitive but not resistant HCC cells. Furthermore, USP3 knockdown was more effective in suppressing anchorage-independent colony formation in chemoresistant HCC cells compared to their chemo-sensitive counterparts. Pearson correlation coefficient analysis revealed a strong positive correlation between USP3 and CTNNB1, and consistently, USP3 knockdown reduced the levels and activities of β-catenin in HCC cells. Using a Wnt activator (lithium) in rescue studies significantly reversed the inhibitory effects of USP3 knockdown. The findings suggest that inhibiting USP3 is an effective strategy against cancer stem cells and chemo-resistant HCC cells.

1226 Early Versus Delayed Fractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma

INTRODUCTION: Stereotactic radiosurgery (SRS) can be used to treat residual or recurrent pituitary adenomas with good control rates. Fractionated stereotactic radiotherapy (FSRT) is a viable alternative with similar outcomes. It is currently unknown whether FSRT should be performed early for residual tumor or delayed until progression occurs. METHODS: A retrospective review of patients who underwent FSRT for a NFPA between January 2004 to December 2022 at a single institution was performed. We compared the endocrinologic, ophthalmologic, and radiographic outcomes in FSRT delivered as ADJ and PRG treatment. RESULTS: 75 patients were analyzed, with a median follow-up of 53 months. FSRT was administered to 35 and 40 patients as ADJ and PRG, with a median time to treatment of 5.5 and 40 months, respectively. The tumor control rate was 94.3% for ADJ and 95.0% for PRG. Treatment resulted in four (11.4%) versus seven (17.5%) new endocrinopathies and two (5.7%) versus one (2.5%) new visual deficits for ADJ versus PRG. A survival analysis of time-to-new endocrinopathy showed no difference between the two cohorts. Median time from surgery to new endocrinopathy was 15.5 months for ADJ and 102.0 months for PRG (p = 0.02). The rate of new endocrinopathy at five years was 22.2% in for ADJ and 18.8% for PRG (p = 0.80). CONCLUSIONS: FSRT is effective in treating NFPA for residual and progressive tumors, with excellent tumor control rates comparable to SRS and a low risk of developing new endocrinopathies and visual deficits. The delayed treatment in the PRG cohort resulted in a greater duration until the development of a new endocrinopathy, suggesting that observation followed by FSRT on tumor progression may delay the onset of hypopituitarism while maintaining similar effectiveness in tumor control.

Similar Effect of Vonoprazan and Oral Proton Pump Inhibitors for Preventing Rebleeding in Cases of Upper Gastrointestinal Bleeding.

Objective The use of a proton pump inhibitor (PPI) reduces rebleeding and mortality in patients with upper gastrointestinal bleeding (UGIB). Vonoprazan is a novel oral agent with strong and sustained acid-inhibitory activity. We clarified the effect of vonoprazan compared with oral PPIs in such patients. Methods We analyzed the Diagnosis Procedure Combination database. The primary outcome was rebleeding, and secondary outcomes were in-hospital mortality and in-hospital mortality after rebleeding. Propensity score matching was performed to balance the comparison groups, and logistic regression analyses were used to compare the outcomes between vonoprazan and oral PPIs. Patients Patients on vonoprazan or oral PPIs who underwent endoscopic hemostasis for UGIB between 2014 and 2019 were included. Results We enrolled 78,964 patients, of whom 27,101 and 51,863 were prescribed vonoprazan and a PPI, respectively. After propensity score matching, the rebleeding rate of vonoprazan did not significantly differ from that of oral PPIs [6.4% vs. 6.1%; odds ratio (OR), 1.05; 95% confidence interval (CI), 0.98-1.13]; similarly, the in-hospital mortality rate (1.4% vs. 1.5%; OR, 0.91; 95% CI, 0.79-1.05) and in-hospital mortality after rebleeding (0.3% vs. 0.2%; OR, 1.09; 95% CI, 0.78-1.54) also did not significantly differ between the groups. The acquired findings were robust across dose-restricted analyses and several sensitivity analyses. Conclusion Rebleeding and in-hospital mortality risks in patients on vonoprazan were similar to those in patients on oral PPIs. Considering the higher cost of vonoprazan, oral PPIs might be an optimal oral agent as an acid-suppressive therapy in such patients.

The Effects of Oxygen Availability in the Seed Container during Storage on Seed Germination in Tomato, Onion, Cabbage, and Marrow Seeds

This research was conducted to test the effect of oxygen content (low O2, high O2, air) during hermetic seed storage at 20±2°C over 8 and 12 months on seed germination and seedling root and shoot length in tomato, onion, cabbage, and marrow seeds. Samples with low oxygen storage had higher seed germination as well as longer root and shoot lengths than both control and high oxygen storage. When the storage period extended from 8 to 12 months, the germination percentages also reduced. However, these results varied among the species. The greatest advantage of low oxygen storage was obtained in tomatoes, which exhibited 15% and 9% higher germination compared to the control after 8 and 12 months of storage, respectively. The longest root and shoot lengths of 6.4 cm and 11.6 cm, respectively, were obtained from the low oxygen storage treatments. A similar positive effect of low oxygen storage was observed in onion and cabbage seeds but not in marrows. Results indicated that oxygen level in the packets during storage can be an effective component to maintain high seed germination and seedling growth potential (seed vigour). The difference in the effect on different species is a matter of further research.

Quantitative Comparison of Liver Volume, Proton Density Fat Fraction, and Time Burden between Automatic Whole Liver Segmentation and Manual Sampling MRI Strategies for Diagnosing Metabolic Dysfunction-associated Steatotic Liver Disease in Obese Patients.

The performance of automatic liver segmentation and manual sampling MRI strategies needs be compared to determine interchangeability. To compare automatic liver segmentation and manual sampling strategies (manual whole liver segmentation and standardized manual region of interest) for performance in quantifying liver volume and MRI-proton density fat fraction (MRI-PDFF), identifying steatosis grade, and time burden. Fifty patients with obesity who underwent liver biopsy and MRI between December 2017 and November 2018 were included. Sampling strategies included automatic and manual whole liver segmentation and 4 and 9 large regions of interest. Intraclass correlation coefficient (ICC), Bland-Altman, linear regression, receiver operating characteristic curve, and Pearson correlation analyses were performed. Automatic whole liver segmentation liver volume and manual whole liver segmentation liver volume showed excellent agreement (ICC=0.97), high correlation (R2=0.96), and low bias (3.7%, 95% limits of agreement, -4.8%, 12.2%) in liver volume. There was the best agreement (ICC=0.99), highest correlation (R2=1.00), and minimum bias (0.84%, 95% limits of agreement, -0.20%, 1.89%) between automated whole liver segmentation MRI-PDFF and manual whole liver segmentation MRI-PDFF. There was no difference of each paired comparison of receiver operating characteristic curves for detecting steatosis (P=0.07-1.00). The minimum time burden for automatic whole liver segmentation was 0.32 s (0.32-0.33 s). Automatic measurement has similar effects to manual measurement in quantifying liver volume, MRI-PDFF, and detecting steatosis. Time burden of automatic whole liver segmentation is minimal among all sampling strategies. Manual measurement can be replaced by automatic measurement to improve quantitative efficiency.

Lethal and sublethal effects of carlina oxide on the aphid Metopolophium dirhodum and its non-target impact on two biological control agents

This study was designed to investigate the acute toxicity (mortality) and sublethal effects (fertility and potential natality) of carlina oxide, the main constituent of Carlina acaulis essential oil (EO), against adults of Metopolophium dirhodum (Walker) (Hemiptera: Aphididae). Moreover, its toxicity was evaluated against two aphid natural enemies, i.e., Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae) and Chrysoperla carnea Stephens (Neuroptera: Chrysopidae). The highest tested concentration (3.0 mL L−1) resulted in 96.7% mortality of adults of the target pest, highlighting that this concentration of carlina oxide had a similar effectiveness as the positive control we used. Furthermore, probit analysis allowed the estimation of a LC50 of 1.06 mL L−1 and a LC90 of 2.58 mL L−1 for the target pest, which resulted in a much higher mortality rate than that found on natural enemies, i.e., A. aphidimyza (6.7 ± 4.7% ± SD when exposed to the aphid LC90) and C. carnea (7.0 ± 5.5% ± SD when exposed to the aphid LC90), showing the limited non-target impact of carlina oxide. The use of LC30 and LC50 of this compound allowed the fertility inhibition of the target pest by 35.68 ± 6.21% and 23.66 ± 10.58%, respectively, and potential natality inhibition of the target pest by 52.78 ± 4.48% and 59.69 ± 5.60%, respectively. Of note, carlina oxide showed excellent insecticidal activity against M. dirhodum, comparable to the commercial insecticide considered. Overall, the low toxicity of carlina oxide toward A. aphidimyza and C. carnea makes it a safe compound for non-target organisms as well as suitable for developing a green insecticide for the management of M. dirhodum and perhaps other insects of agricultural or medical and veterinary interest.

Meta-analysis of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures

To explore clinical efficacy of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures by Meta analysis. Controlled clinical studies on autogenous bone transplantation and bone substitutes in treating tibial plateau fractures published on PubMed,Web of Science,CNKI,Wanfang and other databases from January 2005 to August 2022 were searched by computer. Literature screening and data extraction were performed according to randomized controlled trial(RCT),and the quality of RCT were evaluated by using intervention meta-analysis criteria in Cochrane manual. Meta-analysis of joint depression,secondary collapse rate of articular surface,blood loss,operative time and infection rate between two methods were performed by Rev Man 5.3 software. Seven RCT studies (424 patients) were included,296 patients in bone replacement group and 128 patients in autograft group. Operative time [MD=-16.79,95%CI(-25.72,-7.85),P=0.000 2] and blood loss[MD=-70.49,95%CI(-79.34,-61.65),P<0.000 01] between two groups had statistically differences,while joint depression[MD=-0.17,95%CI(-0.91,0.58),P=0.66],secondary collapse rate of joint surface[RR=-0.74, 95%CI(0.35,1.57),P=0.43],infection rate [RR=1.21,95%CI(0.31,4.70),P=0.78] between two groups had no differences. The effects of bone substitute and autograft for the treatment of tibial plateau fracture have similar effects in terms of joint depression,secondary articular surface collapse rate and infection rate. However,compared with autologous bone transplantation,bone replacement could reduce blood loss and shorten operation time.

Abstract 7282: Comparing TEAD palmitoylation inhibitors with differential TEAD selectivity in combination efficacy with targeted therapies and in renal safety

Abstract Genetic alterations of the Hippo signaling pathway components resulting in YAP/TAZ activation have been reported in a variety of human malignancies. YAP/TAZ activation and functional requirement have also been linked to resistance to targeted therapies by providing the essential survival signal in drug-tolerant persister/dormant cells. As the main drivers for YAP/TAZ recruitment to chromatin, TEAD transcription factors are the major effectors of the Hippo-YAP/TAZ pathway involved in the regulation of cell proliferation, survival, and cell migration. There are four members in the TEAD family: TEAD1, TEAD2, TEAD3, and TEAD4. All four members have a conserved cysteine residue that gets auto-palmitoylated and a highly conserved central pocket in which the palmitate is buried. TEAD auto-palmitoylation is required for TEAD interaction with coactivator YAP/TAZ and transcriptional activity. We have discovered and developed highly potent and selective TEAD auto-palmitoylation inhibitors that interact directly with TEAD by occupying the central palmitate pocket, disrupt YAP/TAZ-TEAD protein interaction, suppress TEAD transcriptional activity, and selectively block NF2-deficient mesothelioma proliferation in vitro and inhibit NF2 mutant tumor growth in vivo. One of these compounds, VT3989, is being evaluated in an ongoing phase 1 clinical trial, where partial responses in mesothelioma patients have been demonstrated, showing for the first time that the Hippo pathway is druggable and that the Hippo pathway is now a validated target for cancer therapy. It remained a question, however, which TEAD members are more important and whether it would be safer and as efficacious to inhibit one TEAD member than multiple TEAD members. Thus, we utilized our TEAD inhibitors with differential TEAD selectivity to determine the importance of TEAD1 selectivity in anti-tumor efficacy and in renal safety. We evaluated the anti-tumor efficacy of several potent TEAD1-selective and pan-TEAD inhibitors in in vivo combination studies using EGFR mutant/KRAS mutant xenograft models. We found that TEAD1-selective TEAD palmitoylation inhibitors are less efficacious than pan-TEAD/multiple-TEAD inhibitors in combination studies with targeted therapies (as such EGFRi and KRASi). In 14-day/28-day rat studies, TEAD1-selective TEAD inhibitors also exhibited proteinuric nephropathy similar to that observed with pan-/multiple-TEAD inhibitors. Therefore, based on our findings, we can conclude that TEAD1-selective TEAD palmitoylation inhibitors can have similar on-target effect on kidneys as TEAD inhibitors with broader TEAD selectivity while having reduced anti-tumor efficacy and durability of response in combination with targeted therapies. Citation Format: Tracy T. Tang, Leonard Post. Comparing TEAD palmitoylation inhibitors with differential TEAD selectivity in combination efficacy with targeted therapies and in renal safety [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7282.

Abstract 701: Preclinical data of a novel DNA-PK inhibitor in combination with radiation therapy shows promise in the treatment of established GBM and lung carcinoma cell lines

Abstract Radiation therapy (RT) is a cornerstone of oncologic therapy for the majority of solid malignancies, and unrepaired DNA double-strand breaks are responsible for radiation-induced cytotoxicity. RT-induced DNA lesions can be repaired by multiple mechanisms including homologous recombination (HR) and non-homologous end joining (NHEJ), and disruption of either of these pathways can enhance cytotoxicity. A key component of the NHEJ pathway is the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), and loss of kinase activity can significantly increase radiosensitivity. Herein we describe the results of our medicinal chemistry campaign to develop a potent and selective DNA-PKcs inhibitor, WNC0901. WNC0901 inhibits DNA-PKcs kinase activity in a cell free system with an IC50 of 0.071 nM and demonstrated at least 30-fold higher sensitivity than other family members (ATM, ATR, mTOR, PI3K). WNC0901 has limited aldehyde oxidase (AO) liability with a T1/2 &amp;gt;2000 min in liver cytosol and is stable for over 120 minutes in the presence and absence of an AO inhibitor. A preliminary pharmacokinetic analysis in wista han rat (IV=2mg/kg, PO=20mg/kg) demonstrated 116% apparent absolute oral bioavailability, 2.6 hour terminal half-life, 33.0 mL/min/kg clearance, and a 2.6% unbound brain-to-plasma partition coefficient (Kpuu). WNC0901 also had favorable pharmacokinetic properties in beagle dog (IV=2mg/kg, PO=20mg/kg) with moderate clearance (8.5 mL/min/kg), high apparent absolute oral bioavailability (131%) with good exposure (AUC=36092 h*ng/mL), moderate half-life (4.28 h), and low protein binding (74.3% fraction unbound). The volume of distribution was moderate in both species (Vss = 1.32 L/kg in wistar han rat and 1.87 L/kg in beagle dog). In cell culture, WNC0901 inhibited autophosphorylation of DNA-PKcs in HT29 cells irradiated with 10 Gy with an IC50 of 32.7 nM and robustly inhibited autophosphorylation in both U251 glioma and A549 lung cancer cell lines at 300 nM in combination with 5Gy. In a clonogenic assay, 5Gy irradiation (10% survival) combined with 100nM WNC0901 demonstrated modestly enhanced cell killing (1.5% survival), and maximal effects were seen at 300nM (0.04% survival, p&amp;lt;0.01). Similar radiosensitizing effects with 300 nM WNC0901 were seen in the A549 cell line (0.2% survival with combination compared to 19% with 5Gy alone, p&amp;lt;0.01). In summary, WNC0901 inhibits DNA-PK kinase activity and provides potent radiosensitization in a GBM and lung cancer cell line. Future studies will assess the combination of WNC0901 and RT in GBM patient-derived xenograft models in vivo. Citation Format: Ann C. Mladek, Danielle L. Burgenske, William F. Elmquist, Wei Zhong, Jann N. Sarkaria. Preclinical data of a novel DNA-PK inhibitor in combination with radiation therapy shows promise in the treatment of established GBM and lung carcinoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 701.

Assessment of optimal combinations of therapeutic probiotics for depression, anxiety, and stress.

Accumulating data show that probiotics may be beneficial for reducing depressive, anxiety, and stress symptoms. However, the best combinations and species of probiotics have not been identified. The objective of our study was to assess the most effective combinations and components of different probiotics through network meta-analysis. A systematic search of four databases, PubMed, Web of Science, Cochrane, and Embase, was conducted from inception to 11 January 2024. The GRADE framework was used to assess the quality of evidence contributing to each network estimate. We deemed 45 trials eligible, these included 4053 participants and 10 types of interventions. The quality of evidence was rated as high or moderate. The NMA revealed that Bifidobacterium exhibited a greater probability of being the optimal probiotic species for improving anxiety symptoms (SMD = -0.80; 95% CI -1.49 to -0.11), followed by Lactobacillus (SMD = -0.49; 95% CI -0.85 to -0.12). In addition, for multiple strains, compared with the other interventions, Lactobacillus + Bifidobacterium (SMD = -0.41; 95% CI -0.73 to -0.10) had a positive effect on depression. The NMA revealed that Lactobacillus and Bifidobacterium had prominent efficacy in the treatment of individuals with anxiety, depression, and combination of Lactobacillus + Bifidobacterium had a similar effect. With few direct comparisons available between probiotic species, this NMA may be instrumental in shaping the guidelines for probiotic treatment of psychological disorders.

A case study on Norwegian commercial harvesting and production of Saccharina latissima (Part 1): Effect of processing seaweed on chemical hazards, allergens, and microbiological hazards

When producing seaweed for human consumption, incorporating a “Food Safety-by-Design approach” can help protect human health and ensure the safety of future consumers. Post-harvest processing of seaweed is one strategy to reduce undesirable compounds. The study aimed to determine the effects of a commercial processing strategy (blanching and fermentation) of Norwegian-harvested Saccharina latissima (sugar kelp) on the presence of prioritized food safety hazards. We compiled and prioritized food safety hazards to be analyzed based on the current impact of the hazard, the analytical feasibility, and the fit of the hazard to the case study site. Twelve prioritized hazards were included in the case study analyses: arsenic (total and inorganic), iodine, cadmium, lead, mercury, copper, zinc, the allergen tropomyosin, Salmonella spp., Bacillus spp., norovirus, and Vibrio spp. We found that blanching was very effective in reducing iodine concentrations but mildly increased the zinc concentration. Fermentation of blanched seaweed further decreased iodine concentrations and had similar effects on inorganic arsenic, cadmium, and zinc. An unintentional increase in copper was observed. Bacillus cereus was detected in a blanched sample and fermented samples. Vibrio alginolyticus seemed to be introduced during blanching, yet fermentation greatly reduced the detection frequency. Our study illustrates the importance of clearly defining the goals of seaweed processing and optimizing the process for food safety hazards. Meanwhile, it is advised to monitor for unintended effects that may occur during processing, such as, in our case, the introduction of copper and pathogens like B. cereus and Vibrio spp. This study serves as an example for seaweed stakeholders on how to consider a Food Safety-by-Design concept and a risk-based approach during seaweed harvest and post-harvest processing.

Properties of an active film based on chitosan/silk fibroin loaded with an essential oil microemulsion and its application in preservation of strawberries

This study aimed to enhance the weak antibacterial activity of silk fibroin (SF) by creating a composite edible coating film. The film was composed of chitosan (CS), SF, and a 3% (v/v) cinnamon essential oil microemulsion (CEOM), which showed excellent inhibition rates of over 99% against two bacteria and four fungi. The resulting film had a transparency of 84.6% and a contact angle of 61.85° on hydrophobic surfaces. In addition, it exhibited a low water vapor permeability of 1.09 × 10−12 g·cm−1·s−1·Pa−1. These properties make it ideal for use in food coating applications. To assess the preservation capabilities of the composite films, strawberries were coated with different films: CS, SF, SF-CEOM, and SF-CS-CEOM. The results showed that the SF-CS-CEOM film had a similar effect to the SF-CEOM film in suppressing the deterioration of strawberries, when compared to the untreated group, and the shelf life of the strawberries was extended from 2 days to 8 days. The SF-CS-CEOM film inhibits oxidation and metabolism by reducing gas exchange, thereby protecting the integrity of cell membranes, maintaining firmness, and reducing weight loss, while delaying the onset of spoilage by inhibiting microbial growth.

CdS nanorods decorated with non-precious metal Bi spheres for photocatalytic hydrogen production

It is well known that precious metals decoration strategies can effectively improve the charge separation efficiency. Unfortunately, the high price limits their large-scale application. Nevertheless, the cheap transition metal Bi has a similar effect as precious metals. Therefore, we take a simple solvothermal method to reduce and aggregate Bi3+ into bismuth nano-spheres (Bi0). CdS nanorods were modified with Bi spheres to create a hybrid material called x% Bi–CdS, which combines a metal and a semiconductor for photocatalytic hydrogen production. The results of the experiment indicate that the hydrogen evolution rate of the 5% Bi–CdS sample is 1501.52 μmol g−1 h−1, which is 4.2 times greater than that of pure CdS nanorods. This significant enhancement in photocatalytic activity can be attributed to the presence of Bi spheres, which induce a surface plasmon resonance (SPR) effect. This effect boosts the absorption of visible light and enhances the separation efficiency of charge carriers. The study not only provides a solution for the preparation of low-cost CdS-based materials, but also confirms the feasibility of inexpensive Bi metals to replace precious metals as co-catalysts to improve the photocatalytic efficiency.

Sociability: Comparing the Effect of Chlorpyrifos with Valproic Acid.

In recent years, exposures to organophosphate pesticide have been highlighted as a possible cause or aggravating factor of autism spectrum disorder (ASD). The present study examined if Wistar rats prenatally exposed to chlorpyrifos (CPF) at a dose of 1mg/kg in GD 12.5-15.5 could express similar behaviors to those exposed to valproic acid (VPA, 400mg/kg) during the same administration window, which is an accepted animal model of autism. The 3-chambered test was employed to evaluate sociability and reaction to social novelty in two experiments, the first in adolescence and the second in adulthood. The results obtained in this study show that animals prenatally treated with CPF or VPA show a similar behavioral phenotype compared to the control group (CNT). In adolescence, the CPF animals showed a negative index in the reaction to social novelty, followed closely by the VPA, while both experimental groups showed a recovery in this aspect during adulthood. This study therefore provides evidence to suggest that prenatal exposure to CPF in rats could have similar effects on certain components of sociability to those seen in autistic models.