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Introduction: A better understanding of the physiological response of silage maize to a mild reduction in nitrogen (N) fertilization and the identification of predictive biochemical markers of N utilization efficiency could contribute to limit the detrimental effect of the overuse of N inputs., Objectives: We integrated phenotypic and biochemical data to interpret the physiology of maize in response to a mild reduction in N fertilization under agronomic conditions and identify predictive leaf metabolic and proteic markers that could be used to pilot and rationalize N fertilization., Methods: Eco-physiological, developmental and yield-related traits were measured and complemented with metabolomic and proteomic approaches performed on young leaves of a core panel of 29 European genetically diverse dent hybrids cultivated in the field under non-limiting and reduced N fertilization conditions., Results: Metabolome and proteome data were analyzed either individually or in an integrated manner together with eco-physiological, developmental, phenotypic and yield-related traits. They allowed to identify (i) common N-responsive metabolites and proteins that could be used as predictive markers to monitor N fertilization, (ii) silage maize hybrids that exhibit improved agronomic performance when N fertilization is reduced., Conclusions: Among the N-responsive metabolites and proteins identified, a cytosolic NADP-dependent malic enzyme and four metabolite signatures stand out as promising markers that could be used for both breeding and agronomic purposes., (© 2024. The Author(s).)

The current investigation involved the isolation of 13 endophytic fungi from Taxus sp. collected in Himachal Pradesh, India. Among these, isolate PAT-3 produced 195.13 mg/L of Taxol in reformative medium broth using microbial fermentation as an alternative source. The PAT-3 isolate was characterized as Mucor circinelloides through morphologic and molecular techniques. The PAT-3 isolate was the only one to exhibit positive results for the Taxol biosynthesis-related genes 10-deacetylbaccatin-III-10-O-acetyltransferase ( dbat ), Baccatin-III, 3: amino, 3 phenylpropanol transferase ( bapt ), and taxadienol-acetyltransferase ( tat ). Furthermore, human breast cancer (MCF-7) and human melanoma cancer (SKMEL-28) cell lines demonstrated the cytotoxicity of Taxol extracted from isolate PAT-3, with IC 50 values of 80.32 µg/mL and 77.21 µg/mL, respectively. To our knowledge, this is the first study that demonstrates the ability of the endophytic fungus M. circinelloides from Taxus sp. in the northern Himalayan region to produce paclitaxel. The study's findings show that Mucor circinelloides is an excellent alternative source of Taxol, and they may pave the way for the production of Taxol at the industrial level in future., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04091-7., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest in the publication., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Colorectal cancer (CRC) is the leading cause of cancer-related mortality among U.S. Hispanics, with screening proven to decrease both incidence and mortality. Despite rising CRC screening rates in the U.S., Hispanic participation remains disproportionately low. Stool-based tests, particularly popular for reaching underserved populations, may enhance screening adherence. This study evaluates the performance of a 1-day versus a 3-day stool-based testing kit in improving screening completion rates and reducing the need for reminder calls in a Hispanic community along the U.S.-Mexico border. In our quasi-experimental observational study, participants aged 45-75 years who were uninsured or underinsured and overdue for CRC screening were recruited. They received colorectal cancer education and no-cost stool-based screening facilitated by promotoras. Participants were randomly assigned to receive a 1-day or 3-day Fecal Immunochemical Test (FIT) kit. The promotoras swapped FIT kit distribution roles midway through the study period to mitigate performance bias. Our analysis covered 6,660 FITs-3,067 using the 3-day kit and 3,593 with the 1-day kit. Results indicated a higher return rate for the 1-day FIT kit (61.3% vs. 58.7%, adjusted odds ratio [aOR] = 1.22, p < 0.001), fewer reminders needed (69.7% vs. 78.1%, aOR = 0.65, p < 0.001), and lower abnormal FIT results (5.3% vs. 8.1%, aOR = 0.61, p < 0.001). Conclusively, the 1-day FIT kit required fewer reminders and significantly improved return rates, suggesting it may be a more effective option for increasing CRC screening completion among hard-to-reach Hispanic populations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Key Message: Different wheat QTLs were associated to the free asparagine content of grain grown in four different conditions. Environmental effects are a key factor when selecting for low acrylamide-forming potential. The amount of free asparagine in grain of a wheat genotype determines its potential to form harmful acrylamide in derivative food products. Here, we explored the variation in the free asparagine, aspartate, glutamine and glutamate contents of 485 accessions reflecting wheat worldwide diversity to define the genetic architecture governing the accumulation of these amino acids in grain. Accessions were grown under high and low nitrogen availability and in water-deficient and well-watered conditions, and plant and grain phenotypes were measured. Free amino acid contents of grain varied from 0.01 to 1.02 mg g -1 among genotypes in a highly heritable way that did not correlate strongly with grain yield, protein content, specific weight, thousand-kernel weight or heading date. Mean free asparagine content was 4% higher under high nitrogen and 3% higher in water-deficient conditions. After genotyping the accessions, single-locus and multi-locus genome-wide association study models were used to identify several QTLs for free asparagine content located on nine chromosomes. Each QTL was associated with a single amino acid and growing environment, and none of the QTLs colocalised with genes known to be involved in the corresponding amino acid metabolism. This suggests that free asparagine content is controlled by several loci with minor effects interacting with the environment. We conclude that breeding for reduced asparagine content is feasible, but should be firmly based on multi-environment field trials., Key Message: Different wheat QTLs were associated to the free asparagine content of grain grown in four different conditions. Environmental effects are a key factor when selecting for low acrylamide-forming potential., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Desirable characteristics of Staphylococcus sp., Streptococcus sp., Bacillus sp., Klebsiella sp., Escherichia coli, and Pseudomonas pseudoalcaligenes isolated from the trachea of healthy turkeys were evaluated as probiotic candidates in the search for new alternatives to solve antimicrobial resistance issues in poultry. In current study phenotypic and genotypic capacity to produce bacteriocin-like substances, efficacy to inhibit the growth of avian pathogens, susceptibility to antimicrobials of bacteria isolated from the respiratory microbiota of healthy turkeys, and the presence of virulence-associated genes (VAGs) predictors of Avian Pathogenic Escherichia coli (APEC) were evaluated. Nine E. coli and one Klebsiella sp. strains produced bacteriocin-like substances, and all harbored the cvaA gene. Some strains also showed antagonistic activity against APEC. Multidrug-resistant profile was found in 54% of the strains. Six strains of bacteriocin-like substances producing E. coli also harbored 3-5 VAGs. The study showed that two bacterial genuses (Klebsiella sp. and E. coli) present desirable probiotic characteristics. Our results identified strains with potential for poultry's respiratory probiotic., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Sodium fluoroacetate (FA) is a metabolic poison that systemically inhibits the tricarboxylic acid (TCA) cycle, causing energy deficiency and ultimately multi-organ failure. It poses a significant threat to society because of its high toxicity, potential use as a chemical weapon and lack of effective antidotal therapy. In this study, we investigated cell-permeable succinate prodrugs as potential treatment for acute FA intoxication. We hypothesized that succinate prodrugs would bypass FA-induced mitochondrial dysfunction, provide metabolic support, and prevent metabolic crisis during acute FA intoxication. To test this hypothesis, rats were exposed to FA (0.75 mg/kg) and treated with the succinate prodrug candidate NV354. Treatment efficacy was evaluated based on cardiac and cerebral mitochondrial respiration, mitochondrial content, metabolic profiles and tissue pathology. In the heart, FA increased concentrations of the TCA metabolite citrate (+ 4.2-fold, p < 0.01) and lowered ATP levels (- 1.9-fold, p < 0.001), confirming the inhibition of the TCA cycle by FA. High-resolution respirometry of cardiac mitochondria further revealed an impairment of mitochondrial complex V (CV)-linked metabolism, as evident by a reduced phosphorylation system control ratio (- 41%, p < 0.05). The inhibition of CV-linked metabolism is a novel mechanism of FA cardiac toxicity, which has implications for drug development and which NV354 was unable to counteract at the given dose. In the brain, FA induced the accumulation of β-hydroxybutyrate (+ 1.4-fold, p < 0.05) and the reduction of mitochondrial complex I (CI)-linked oxidative phosphorylation (OXPHOS CI ) (- 20%, p < 0.01), the latter of which was successfully alleviated by NV354. This promising effect of NV354 warrants further investigations to determine its potential neuroprotective effects., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although cancer is the leading cause of death among Mexican-Americans, few community-based programs target obesity reduction as a way to reduce the prevalence of obesity-related cancer in underserved populations. Evidence suggests that obesity correlates with 13 types of cancer. The objective is to provide an overview of evaluation and selection of evidence-based content; details of the implementation process; modifications needed to tailor education programs to specific needs of different target audiences; and demonstrate challenges of implementing a community-based prevention program intended to reduce cancer incidence and mortality in Mexican-Americans. We used the Social Cognitive Theory (SCT) to develop a 10-topic menu of educational classes using elements of multiple evidence-based curricula. Outcome measures for physical activity and nutrition were determined using the International Physical Activity Questionnaire (IPAQ) and the Dietary Screener Questionnaire (DSQ). Weight status was determined using weight, body fat, and body mass index (BMI). To date, 2845 adults received wellness education from our program. Multiple delivery models were used to reach a larger audience; they included a 4-week model, 5-week model, employer model, low-income housing, 1- and 2-h sessions, and clinic encounters. Individuals were given education at multiple community locations including senior centers (14%), churches (0.6%), employers (17.6%), low-income housing (8.2%), community centers (16.6%), clinics (11.5%), and schools (32.5%). Our study indicates that our delivery model is feasible and can disseminate evidence-based obesity education. Further investigation is necessary to assess long-term behavioral change and to assess the most effective model for delivery., (© 2021. The Author(s).)

Introduction: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV). The purpose of this ongoing study is the preliminary development of a porcine model of CO poisoning for investigation of alterations in brain mitochondrial physiology., Methods: Four pigs (10 kg) were divided into two groups: Sham (n = 2) and CO (n = 2). Administration of a dose of CO at 2000 ppm to the CO group over 120 minutes followed by 30 minutes of re-oxygenation at room air. The control group received room air for 150 minutes. Non-invasive optical monitoring was used to measure CIV redox states. Cerebral microdialysis was performed to obtain semi real-time measurements of cerebral metabolic status. At the end of the exposure, fresh brain tissue (cortical and hippocampal) was immediately harvested to measure mitochondrial respiration. Snap frozen cortical tissue was also used for ATP concentrations and western blotting., Results: While a preliminary ongoing study, animals in the CO group showed possible early decreases in brain mitochondrial respiration, citrate synthase density, CIV redox changes measured with optics, and an increase in the lactate-to-pyruvate ratio., Conclusions: There is a possible observable phenotype highlighting the important role of mitochondrial function in the injury of CO poisoning., (© 2022. American College of Medical Toxicology.)

Introduction: Accuracy of feature annotation and metabolite identification in biological samples is a key element in metabolomics research. However, the annotation process is often hampered by the lack of spectral reference data in experimental conditions, as well as logistical difficulties in the spectral data management and exchange of annotations between laboratories., Objectives: To design an open-source infrastructure allowing hosting both nuclear magnetic resonance (NMR) and mass spectra (MS), with an ergonomic Web interface and Web services to support metabolite annotation and laboratory data management., Methods: We developed the PeakForest infrastructure, an open-source Java tool with automatic programming interfaces that can be deployed locally to organize spectral data for metabolome annotation in laboratories. Standardized operating procedures and formats were included to ensure data quality and interoperability, in line with international recommendations and FAIR principles., Results: PeakForest is able to capture and store experimental spectral MS and NMR metadata as well as collect and display signal annotations. This modular system provides a structured database with inbuilt tools to curate information, browse and reuse spectral information in data treatment. PeakForest offers data formalization and centralization at the laboratory level, facilitating shared spectral data across laboratories and integration into public databases., Conclusion: PeakForest is a comprehensive resource which addresses a technical bottleneck, namely large-scale spectral data annotation and metabolite identification for metabolomics laboratories with multiple instruments. PeakForest databases can be used in conjunction with bespoke data analysis pipelines in the Galaxy environment, offering the opportunity to meet the evolving needs of metabolomics research. Developed and tested by the French metabolomics community, PeakForest is freely-available at https://github.com/peakforest ., (© 2022. The Author(s).)

Cancer carries stigma, taboos, and shame including, for diverse communities, who can have difficulty understanding and communicating about family health history genetic cancer screening (GCS). The Oregon Health Authority ScreenWise Program reached out to our academic-community research team to explore Asians and Micronesian Islanders (MI) perceptions on public health education outreach on GCS due to having previously only worked with the Latinx community. The purpose of the qualitative description pilot study was to elicit perceptions, beliefs, experiences, and recommendations from Asian and MI community leaders and community members regarding family health history GCS outreach in communities. Twenty Asians (Chinese and Vietnamese) and Micronesian Islanders (Chuukese and Marshallese) were recruited from the US Pacific Northwest. Nineteen participants are immigrants with an average 21.4 and 18.5 years having lived in the USA, respectively. Individual in-depth interviews were conducted using a semi-structured, open-ended interview guide and analyzed using conventional content analysis. Three main transcultural themes were identified: (1) degree of knowing and understanding cancer screening versus family health history GCS, (2) needing culturally relevant outreach messaging on family health history GCS, and (3) communication and decision-making regarding discussing with family and health care providers about cancer screening and GCS. Culturally relevant messaging rather than generic messaging is needed for inclusive outreach. Healthcare providers are encouraged to assess a client's family health history routinely because Asian and MI clients may not understand the information requested, may be hesitant to offer, or unable to provide information about their personal or family history of cancer., (© 2021. American Association for Cancer Education.)

Obesity is a serious public health problem within the United States. One promising approach to obesity prevention is health behavior change among college students, focusing on diet, sleep, and exercise. However, it remains unclear whether a health behavior change promotion program implemented in the classroom will effectively improve these health behaviors and negative outcomes related to obesity, particularly within classes of different topics. We examined the impact of a 6-week health behavior change program based on the Theory of Planned Behavior. Across several years, with two seemingly distinct samples of students from either a health psychology (n = 433) or a home gardening (n = 155) course, we conducted two studies and employed a single group, pre/post design in which self-reported and objectively measured health outcomes were assessed for change relative to the health promotion program. Participants selected one of three health behaviors and sought to meet current Centers for Disease Control and Prevention recommendations by setting goals, tracking behavior, and meeting with social support groups. Within both studies, dramatic changes emerged in the targeted health behaviors of fruit and vegetable consumption, sleep quantity and quality, and exercise. Moreover, several other health indicators improved among our subjective and objective health variables, and a few outcomes (i.e., subjective health, sleep quality, flexibility, loneliness) improved across all health behavior groups. Collectively, these results suggest this health behavior change program may be an effective way to elicit behavior change and highlight avenues for future remediation and prevention of obesity and related disease.

The plasma membrane Ca 2+ -ATPase (PMCA) removes Ca 2+ from the cytosol into the extracellular space. Its catalytic activity can be stimulated by calmodulin (CaM) or by limited proteolysis. We evaluated the effect of chlorpromazine (CPZ) and dimethyl sulfoxide (DMSO) over the hydrolytic activity of PMCA. Activity was monitored in three different forms: native, CaM-activated and proteolyzed by trypsin. CPZ appears to inhibit PMCA without directly interfering with the C-terminal site, since it is affected by CaM and proteolysis. Although the treatment of PMCA with trypsin and CaM produces an activation, it also produces an enzymatic form that is more sensitive to inhibition by CPZ. The same case was observed in the DMSO inhibition experiments. In the absence of CPZ, DMSO produces a progressive loss of activity, but in the presence of CPZ the profile of activity against DMSO changes and produces a recovery of activity, indicating a possible partition of CPZ by the solvent. Increasing Ca 2+ concentrations indicated that CPZ interacts with PMCA rather than with CaM. This observation is supported by docking analysis that suggests that the CPZ-PMCA interaction is non-competitive. We propose that CPZ interacts with the state of lower affinity for Ca 2 + .

Purpose: Axitinib, an orally administered inhibitor of vascular endothelial growth factor 1, 2 and 3, is primarily metabolized by cytochrome P450 (CYP) 3A4/5 but is also a substrate for CYP1A2, CYP2C19, UDP-glucuronosyltransferase (UGT)1A1 and the drug transporters P-glycoprotein (encoded by the ABCB1 gene) and OATP1B1 (encoded by SLC01B1). The potential contribution of polymorphisms in genes encoding these enzymes and transporters to axitinib pharmacokinetic variability was assessed., Methods: A fixed effects meta-analysis was performed using data pooled from 11 healthy volunteer clinical pharmacology trials to investigate the potential association between axitinib exposure and major polymorphisms in these genes following a 5-mg dose of axitinib., Results: Up to 15 variant alleles were evaluated and up to 315 healthy volunteers per polymorphism were assayed. None of the polymorphisms analysed was a statistically significant predictor of axitinib pharmacokinetic variability. Amongst genotypes and inferred phenotypes, CYP2C19 genotype and the ABCB1 (G2677T/A) polymorphism were the closest to statistical significance in influencing axitinib pharmacokinetic variability after multiple-testing adjustment. However, no enzyme or transporter genotype/inferred phenotype contributed >5% to the overall pharmacokinetic variability of axitinib., Conclusions: No statistically significant associations between the specific polymorphisms analysed and axitinib plasma exposure were observed, suggesting that genotype- or inferred phenotype-based adjustment of axitinib dose in individual subjects is not warranted.

The objectives of this study were to determine the concentrations of free benzalkonium chloride (BAC) and apparent partitions coefficients (Km) in micelle solutions and to explore its application in formulation development. Ultrafiltration (UF) was carried out using 10K Nanosep devices and centrifugation at 5,000 rpm for 5 min. The separation of free BAC from micellar solutions was also conducted using ultracentrifugation (UC) method for the comparison with UF method. Capillary electrophoresis method was used for the identification of micelles. Results showed that a UF method was applicable for quantitatively evaluating BAC-micelle interaction in micellar solutions. Unlike UF, UC could not completely separate free BAC from the micelles. The free BAC concentrations in the micelle solutions decreased with increasing surfactant concentrations. Among polysorbate 80, cremophor EL, and tyloxapol, BAC had the highest Km in polysorbate 80 solutions. The Km was significantly lower in non-buffered aqueous solutions than that in citric buffers. Moreover, increasing surfactant concentrations led to reducing antimicrobial activity. The UF is a rapid and accurate method that minimally alters the micellar equilibrium for the determination of free BAC and Km in micellar solutions. In conclusion, free BAC concentration, which is a function of surfactant type, surfactant concentration, and ion strength of solution, is likely associated with the antimicrobial activity.