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Exogenous estradiol does not regulate daily metabolic rhythms underlying diet-induced obesity in male mice

Male mice fed high-fat diet become obese, but female mice are resistant to diet-induced weight gain. We previously found that circulating estradiol in females protects their daily rhythms from disruption by high-fat feeding to prevent diet-induced obesity. The goal of this study was to determine the effects of estradiol on daily metabolic rhythms in male mice. Male C57BL/6J mice were treated with estradiol and fed high-fat diet for 2 weeks. We measured the effects of high-fat diet feeding on daily rhythms of eating behavior and locomotor activity, and on the phases, or timing, of circadian rhythms in central and peripheral tissues. We found that males treated with estradiol had lower blood glucose when fed high-fat diet than males treated with vehicle even though there were no effects of estradiol treatment on body weight and adiposity. There was no effect of estradiol on the daily rhythm of eating behavior as it was low-amplitude or arrhythmic during high-fat diet feeding in both vehicle- and estradiol-treated males. Locomotor activity rhythms were also unaffected by estradiol treatment. Likewise, the phases of circadian rhythms in the suprachiasmatic nucleus (SCN), liver, muscle, and other peripheral tissues were not altered by estradiol treatment. Thus, treatment of male mice with estradiol did not protect daily rhythms from disruption by high-fat diet, as it does in females. Together these data suggest that the mechanisms underlying sex differences in daily metabolic rhythms are complex and may require both developmental and adult exposure to hormones.

Regulating female ear morphogenesis in maize by uniconazole and 5-aminolevulinic acid for yield improvement

Expert evaluation of LLM world models: A high-T _<i>c</i> superconductivity case study

Large Language Models (LLMs) show great promise as a powerful tool for scientific literature exploration. However, their effectiveness in providing scientifically accurate and comprehensive answers to complex questions within specialized domains remains an active area of research. Using the field of high-temperature cuprates as an exemplar, we evaluate the ability of LLM systems to understand the literature at the level of an expert. We construct an expert-curated database of 1,726 scientific papers that covers the history of the field, and a set of 67 expert-formulated questions that probe deep understanding of the literature. We then evaluate six different LLM-based systems for answering these questions, including both commercially available closed models and a custom retrieval-augmented generation (RAG) system capable of retrieving images alongside text. Experts then evaluate the answers of these systems against a rubric that assesses balanced perspectives, factual comprehensiveness, succinctness, and evidentiary support. Among the six systems, two using RAG on curated literature outperformed existing closed models across key metrics, particularly in providing comprehensive and well-supported answers. We discuss promising aspects of LLM performances as well as critical short-comings of all the models. The set of expert-formulated questions and the rubric will be valuable for assessing expert level performance of LLM based reasoning systems.

Silence in physician clinical practice: a scoping review protocol

Objective The objective of this review is to map, describe and conceptualize how silence is discussed within literature on interactions between physicians and patients, in clinical settings. Methods We will use the methodological framework of Arksey &amp; O’Malley, adapted by Levac et al and Joanna Briggs Institute. Empirical studies including quantitative, qualitative, mixed methods, observational studies and reviews will be included. Commentaries, editorials, and grey literature will also be examined. The databases MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Scopus and Web of Science will be searched. A two-part study selection strategy will be applied. First, reviewers will follow inclusion and exclusion criteria based on ‘Population-Concept-Context’ framework to independently screen titles and abstracts. Next, full texts will be screened. Data will be extracted, collated, and charted to summarize methods, outcomes and key findings from the articles included. Findings will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews. (PRISMA-ScR). Expected results and implications This scoping review will provide an extensive description of how physicians engage with silence in clinical settings. Findings will identify how silence is perceived in physician patient interactions, the roles it plays, what factors influence use of silence and guide development of educational initiatives on use of silence in clinical settings.

Author Correction: Molecular discernment and histopathological features of oncogenic Marek’s disease virus among different farmed avian species in Egypt

Crystal structure of <i>Vibrio cholerae</i> polysaccharide lyase RbmB bound to <i>Vibrio</i> polysaccharide (VPS) fragments provides insights into substrate recognition and cleavage

Exopolysaccharides are carbohydrate polymers secreted by bacteria to perform various roles including adhesion to surfaces, protection from environmental stressors, and as key components in the production of biofilms. The human pathogen Vibrio cholerae produces an exopolysaccharide called VPS, which is essential for the formation of its biofilm matrix through crosslinking interactions with a series of secreted accessory proteins. VPS consists of a repeating tetrasaccharide unit consisting of a uniquely modified α-L-gulose moiety (with N-acetyl, O-acetyl, and amide-linked glycine modifications). Encoded within the cluster containing the biofilm-production genes is a glycoside lyase called RbmB, which cleaves VPS and has been implicated in biofilm dispersal. Here we describe the ~2 Å X-ray structure of RbmB bound to tetrameric and octameric fragments of VPS representing 10 total monosaccharides of an enzyme–product complex. The structure, along with molecular dynamics simulations and complementary functional analyses of mutant proteins in vitro and in vivo, illustrates how recognition and cleavage of VPS relies on salt-bridging interactions between arginine residues in RbmB and the amide-linked glycine moiety uniquely found on the VPS L-gulose and a ~30° bend near the cleavage site that strains the scissile bond. We further present results regarding the localization of RbmB in V. cholerae cells, suggesting that cleavage of VPS by RbmB likely takes place in the periplasm. Sequence conservation suggests that homologous biofilm systems found in many Vibrio species likely utilize a similar VPS cleavage mechanism suggesting that RbmB could be an effective tool for dispersing biofilms across the Vibrio genus and beyond.

Estimation of Respiratory Syncytial Virus-attributable hospitalizations among older adults in Japan between 2015 and 2018: An administrative health claims database analysis

We estimated the incidence rates (IRs) of respiratory syncytial virus (RSV)-related hospitalizations among adults aged ≥60 years in Japan from 2015 to 2018, using a time-series model-based approach to better understand the disease burden. We obtained hospitalization data from the Medical Data Vision (MDV) database, restricted to Diagnosis Procedure Combination (DPC) hospitals. We estimated the annual age-specific RSV-attributable IR of hospitalizations for five cardiorespiratory outcomes based on selected ICD-10 codes employing a quasi-Poisson regression model. We projected our results to all DPC hospitals in Japan and also to all Japanese hospitals. In adults aged ≥60 years, the annual IR of RSV-attributable cardiorespiratory hospitalizations at DPC hospitals was estimated at between 100 and 124 per 100,000 person-years, projecting to 134–229 cardiorespiratory hospitalizations per 100,000 person-years at all hospitals. For respiratory hospitalizations at DPC hospitals, the annual IR was from 69 to 85 per 100,000 person-years (projecting to 96–157 hospitalizations per 100,000 person-years at all hospitals). IRs for all outcomes were consistently higher among adults aged ≥80 years than those 60–79 years. Our results indicate a high burden of RSV-attributable hospitalizations in older adults in Japan, highlighting the need to implement effective RSV prevention strategies.

Sustainable regional corn yield prediction for the United States through interpretable machine learning approach

Abstract Considering crop yield prediction as critical to optimizing agricultural practices and food security, this question is critical to U.S. agricultural planning and regional food security; relevant research on corn, one of the essential crops, must focus on the accurate methods for predicting this crop. It has been discussed that yield prediction models generally rely on simplistic approaches, which fail to capture complex, non-linear relationships in agricultural data. This work fills the knowledge gap by making use of advanced machine-learning techniques to improve the accuracy of corn yield prediction. This study focuses on county-level regional forecasting(U.S) to support agricultural policy and supply chain planning rather than field-specific management decisions. The methodology is in line with the Special Section on Sustainable Computing for Next-Generation Low-Carbon Agricultural Consumer Electronics by designing a data-efficient algorithm that focuses on the Random Forest Classifier, Gradient Boosting Classifier, and Ensemble Voting Classifier. The development of this model entailed the pre-processing of historical data concerning corn yield, defining pertinent attributes, and assessing the confusion matrix, ROC curve, and SHAP values for explainability. This work proposes an ensemble model which has achieved remarkable accuracy and robustness, excelling in performance relative to the existing approaches. The model has also made solid predictions, with a precision, recall, and F1-score of 0.92 and a training accuracy of 0.97. The SHAP further enhances transparency into the features that drive predictions, hence making the model more interpretable. This is of great importance to agricultural planning; this would most probably offer a sound instrument to predict corn yield and optimize resources in agricultural consumer practices. This paper strongly advocates energy-efficient algorithm design, intelligent applications, sustainable computing, efficiency, environmental impact, and resource recycling to drive toward sustainable and efficient corn yield prediction.

Mixed-mobility supported lipid bilayers uncover the role of immobilized ICAM1 on T cell activation and immune synapse organization

The immunological synapse (IS) integrates antigen recognition and adhesion to control T cell activation and effector functions. Reductionist systems have been instrumental in dissecting IS organization, but conventional systems constrain all ligands to be either mobile or immobile, unlike antigen-presenting cells where intercellular adhesion molecule 1 (ICAM1) is cytoskeletally anchored while T cell receptor (TCR) ligands remain mobile. Here, we establish mixed-mobility supported lipid bilayers (SLBs) that simultaneously present mobile TCR agonists and immobile ICAM1. Selective immobilization of ICAM1 disrupts centripetal F-actin flow, prevents centralization of TCR microclusters and shifts signaling to peripheral microclusters. This attenuates TCR downregulation through ectocytosis while maintaining recycling, and enhances integrin mechanotransduction, reflected in increased phosphorylation of Focal Adhesion Kinase, Paxillin, and the stretch-sensitive adaptor CasL. Functionally, immobilized ICAM1 augments T cell activation, degranulation, Perforin release, and cytotoxicity. Importantly, these findings were recapitulated in a cell–cell system engineered to express either full-length, cytoskeleton-anchored ICAM1 or a truncated form lacking cytoskeletal association, with full-length ICAM1 consistently promoting stronger effector responses. These findings identify ligand mobility as a key biophysical parameter that shapes IS organization and T cell effector responses and establish mixed-mobility SLBs as a powerful tool for probing receptor mechanics in immunity.

Distribution and evolution of the LysR-type transcriptional regulators of the Salmonella genus

LysR-type transcriptional regulators (LTTRs) are one of the most abundant transcriptional regulators in nature and are involved in multiple essential biological process in bacteria. In this work we show that LTTRs are highly abundant in Salmonella enterica subspecies enterica serovars able to infect humans ( S. Typhi), whereas the number of LTTRs decreases substantially in reptile commensals ( Salmonella enterica subspecies arizonae , diarizonae , houtenae , indica, salamae and Salmonella bongori ). In addition, it is also reported the presence of a Salmonella LTTR core, LTTRs exclusive to the Salmonella genus and LTTRs like CysB that is widely distributed in the Enterobacteriales order and their orthologous sequences separate clades at the genus level, suggesting that CysB has evolved in parallel with the corresponding lineage. Therefore, there are LTTRs that evolved as part of the core of microorganisms that provide essential genetic functions to the cell, as well as a LTTR accessory pool that provides different capabilities to specific microorganisms for survival in nature and in different environments of the host.

A comparative analysis of crossovers in genetic algorithms for route optimization: case studies from Astana and Shymkent, Kazakhstan

The membrane-associated ubiquitin ligase MARCHF8 degrades MHC-I in HPV-positive head and neck cancer for immune evasion

The loss of major histocompatibility complex class I (MHC-I) molecules has been proposed as a mechanism for cancer immune evasion. Nevertheless, the mechanism is poorly understood. We report here that membrane-associated RING-CH-type finger 8 (MARCHF8), upregulated by human papillomavirus (HPV), ubiquitinates and degrades MHC-I in HPV-positive head and neck cancer (HPV+ HNC). Inhibiting MARCHF8 restores MHC-I levels on HPV+ HNC cells, suppresses tumor growth, and increases the infiltration of natural killer (NK) and T cells in the tumor microenvironment. Furthermore, Marchf8 knockout markedly increases cross talk between cytotoxic NK cells and CD8 + T cells with macrophages and enhances the tumor-killing activity of CD8 + T cells. Interestingly, Marchf8 knockout, in combination with anti-PD-1 treatment, further enhances tumor suppression and increases NK and T cell infiltration in mice bearing immune checkpoint inhibitor–refractory tumors. Our findings suggest that MARCHF8 could be a promising target for immunotherapy for HPV+ HNC patients.

Expression of Concern: Ezrin interacts with the tumor suppressor CHL1 and promotes neuronal differentiation of human neuroblastoma

A computational microscope for fluctuations: Bringing crystal nucleation into focus

Prevalence and risk factors of asymptomatic bacteriuria in community-dwelling Korean adults

The clinical characteristics of asymptomatic bacteriuria (ASB) in community-dwelling Asian adults remain underexplored. We aimed to identify the potential risk factors for ASB in an Asian population. We conducted a cross-sectional analysis of 8,508 participants. Urinary bacteria were quantified using urine flow cytometry and semi-quantitatively reported on a scale from negative to 3 + . For this epidemiologic analysis, bacteriuria was operationally defined as a flow cytometry result of ≥1 + , rather than by culture-based criteria. ASB was defined as bacteriuria accompanied by a self-reported negative answer to the question: “Have you recently experienced any sudden and frequent need to urinate?” The overall prevalence of ASB was 4.6%, with rates of 5.9% in women and 1.0% in men under 50, and 9.5% in women and 1.6% in men over 50. Older age, women, and diabetes were associated with increased odds of having ASB, whereas high physical activity and serum albumin levels were associated with decreased odds. Regardless of age, diabetes status, and physical activity and serum albumin levels, women showed higher odds of ASB than did men. Men and women with high physical activity and serum albumin levels showed lower odds of ASB than those without high levels. Age, sex, diabetes, physical activity, and serum albumin levels were independently associated with ASB among community-dwelling Korean adults. Future studies need to confirm the potential beneficial association of high physical activity and serum albumin levels with ASB in men and women.

A wireless sweat sensing with a pH-based correlation model for continuous glucose monitoring and diabetes management during exercise

In situ monitoring of sweat glucose during exercise can provide a real-time and continuous assessment of blood glucose dynamics. However, the relatively poor correlation between sweat and blood glucose concentrations during exercise makes it challenging for blood glucose management (BGM) during exercise therapy for diabetes, along with training for athletes and fitness enthusiasts. This work presents a flexible wireless sweat glucose and pH sensing platform integrated with a pH-based correlation model to accurately predict the continuous changes in blood glucose. The pH-based correlation model calibrates enzyme activity changes in glucose oxidase and accounts for the effects of sweat dilution and filtering during paracellular transport of glucose from interstitial fluid and plasma to sweat during exercise. The correlation model has been validated in both healthy individuals and diabetic patients, revealing distinct blood glucose dynamic patterns between the two cohorts. The observed different glucose fluctuations after the intake of various nutritive foods further facilitate the management of diabetes and allow for the identification of hypo-/hyperglycemic risks during training or fitness exercise. The exercise-based device platform combines continuous blood glucose monitoring with diabetes management through effective treatment evaluation and can also provide early prevention for the at-risk population and reduce or even reverse diabetes.

Effects of the incorporation of honey from Apis mellifera from the Amazon savanna on the technological and sensory properties of yogurt during refrigerated storage

The development of new yogurt formulations that provide additional health benefits has gained prominence in recent years. The objective of this study was to characterize the physicochemical, antioxidant, technological, microstructural and sensory properties of the honey of Apis mellifera bees from the Amazon savanna and evaluate its inclusion at different concentrations (8%, 12%, 16% and 20%) of yogurt during 28 days of refrigerated storage. The results showed that honey is within the recommended quality parameters for this product. The amount of added honey had positive effects on the color characteristics, water holding capacity and total solids content (P &lt; 0.05), increasing the nutritional value of the yogurt. The highest concentrations of honey (16% and 20%) presented relatively high antioxidant activity (measured via the DPPH method) and were the most sensorially accepted (P &lt; 0.05) by consumers. In addition, the highest concentration of honey (20%) favored the stability of syneresis and resulted in higher levels of total polyphenol compounds (P &lt; 0.05). In conclusion, the addition of honey from Apis mellifera from the Amazon savanna to yogurt formulation proved to be an effective strategy to improve the quality and acceptability of the final product. In addition to standing out as a promising ingredient for the development of functional foods, its incorporation represents a relevant innovation for the local food sector, with new perspectives for the creation of differentiated products aligned with the contemporary demands for healthy and sustainable foods.

Psoriasis-like disease prevents squamous skin tumor development by neutrophil-driven inflammation

Psoriasis is a chronic inflammatory skin disease affecting millions of people worldwide. Although growing evidence links chronic inflammation with increased cancer risk, the association between psoriasis and cutaneous squamous cell carcinoma (cSCC) is still elusive. Using cell transplantation and chemical-induced models of cSCC combined with inducible genetically engineered mouse models of psoriasis, we investigated how chronic skin and systemic inflammation affects squamous skin tumor initiation and progression. Here we show that in the context of severe psoriasis-like disease, neutrophil-dependent inflammation prevents squamous skin tumor development. Cellular and molecular analyses of psoriasis-like skin at the tumor initiation stage revealed a marked infiltration of CD54–expressing neutrophils, associated with the release of cytotoxic granules and neutrophil extracellular traps (NETs), as well as enhanced senescence and the expression of senescence-associated secretory phenotype in keratinocytes. Furthermore, single-cell RNA sequencing demonstrated that inflammatory N1-like neutrophils mediate reprogramming of the cell–cell communication networks, while keratinocytes displayed diminished responsiveness to mitogenic signals, including epidermal growth factor and Wnt/β-catenin. Importantly, neutrophil depletion ameliorated psoriasis-like inflammation, abolished the senescence-like phenotype in keratinocytes and restored tumor growth. We propose that the release of neutrophil granules and NETs in psoriasis-like skin eliminate tumor cells and/or mediate oxidative and inflammatory stress-induced senescence in keratinocytes, thereby preventing tumor growth. Taken together, we have defined an innate control of skin tumorigenesis in psoriasis-like disease, which will be relevant for developing cancer prevention strategies.

The role of physical activity in modulating six-minute walk distance in adolescents

Purpose The six-minute walk test (6MWT) is one of the most widely utilized submaximal tests to assess cardiorespiratory fitness in both healthy and clinical populations. The present study aims to provide 6MWT reference values for Italian adolescents (11–18 years) and to identify key variables influencing the six-minute walk distance (6MWD). Methods Data were collected from 3276 Italian adolescents (48% males). Participants provided self-reported age, height, weight, and weekly practice of moderate-to-vigorous physical activity (MVPA). 6MWT was performed to assess participants’ cardiorespiratory fitness. Results Average distances of 730.0 (IQR: 674.0–788.0) and 675.0 (IQR: 624.0–720.0) meters were walked in the 6MWT by male and female adolescents, respectively. Multiple linear regression models, used to investigate whether demographics, anthropometrics, and MVPA predicted the 6MWD, revealed statistically significant results in both males ( p  &lt; .001, F = 28.94, adjusted R 2  = 0.11) and females ( p  &lt; .001, F = 23.00, adjusted R 2  = 0.09). In male adolescents, MVPA and age positively predicted the 6MWD, whereas BMI negatively predicted the 6MWD. In female adolescents, MVPA positively predicted 6MWD, whereas age and BMI negatively predicted 6MWD. No interaction effects were found. Conclusion The reference percentiles of distance walked, classified by sex and age, reported in the present study can be used as a practical tool to assess adolescents’ cardiorespiratory fitness. This study also highlights the importance of PA engagement in this population, as it was considerably associated with the average distance walked. Consequently, in addition to anthropometric and demographic variables, future studies should pay particular attention to the amount of MVPA practiced.

Banana aroma is a result of acetohydroxyacid synthase and isopropylmalate synthase alternative isoforms that bypass feedback inhibition

The distinctive aroma of banana fruit ( Musa spp.) results from the upregulation of a pathway that is, paradoxically, understood to be feedback limited. The primary character impact compounds in banana are branched-chain esters with 3-methylbutyl moieties. Recent work has established that these esters, as well as prominent “fruity” 2-methylpropyl and butyl esters, are derived from the ripening-dependent de novo synthesis of the branched-chain amino acids valine and leucine, and their respective α-ketoacid precursors. The biosynthetic pathway possesses two sequential, rate-limiting, and feedback-inhibited enzymes: acetohydroxyacid synthase and isopropylmalate synthase. We found these enzymes to be alternatively spliced in ripening banana fruit pulp. Unripe fruit and nonfruit tissues had only trace levels of alternative splicing. Revealingly, the domains corresponding to the allosteric inhibitory binding of valine and/or leucine were truncated in the altered isoforms. During ripening, the expression and frequency of the shorter splice forms increased concomitantly with production of branched-chain esters and accumulation of their α-ketoacid precursors. Purified proteins of the modified isoforms were active but relieved of feedback inhibition. Transient expression of the shortened isoforms in Nicotiana benthamiana led to a greater accumulation of iso -branched-chain metabolites than the full-length isoforms. Results indicate that a developmentally dependent and simultaneous dysregulation in two sequential steps of the branched-chain amino acid synthetic pathway enables the biosynthesis of banana fruit’s unique character-impact esters.