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A novel zinc oxide/schwertmannite composite for efficient remediation of oxytetracycline contamination

The insulin-like peptides Dilp2 and Dilp6 exhibit divergent responses to dietary sugar and protein in <i>Drosophila</i> larvae

Nutrient intake drives secretion of insulin and insulin-like peptides that stimulate anabolic metabolism and tissue growth. Eight Drosophila insulin-like peptides (Dilps) are encoded in the Drosophila genome; whether these Dilps respond uniformly to changes in dietary nutrients is unknown. Here, we investigate the endocrine responses of Dilp2, secreted by brain insulin-producing cells, and Dilp6, produced by the fat body, to dietary sugar and protein in mid-third instar Drosophila larvae. Starvation leads to a profound reduction in circulating Dilp2 without affecting circulating Dilp6 levels. Diets containing sugar alone drive nutrient storage and increase hemolymph Dilp6, but do not promote Dilp2 release. In contrast, dietary protein drives growth and restores hemolymph Dilp2 but strongly reduces circulating Dilp6. Furthermore, circulating levels of Dilp2 and Dilp6 are modulated by the ratio of sugar to protein in the diet. We find that depleting circulating Dilp6 via fat body specific knockdown or increasing insulin receptor (InR) levels in fat body leads to increased levels of triglyceride storage but decreased peripheral growth. Our results suggest that Dilp6, a hormone produced in response to dietary sugar, may direct the use of sugar for growth instead of fat storage at the end stage of larval development. Our findings reveal different modes of regulation for Dilp2 and Dilp6 and raise the question of how the single known Drosophila InR integrates divergent signals from distinct Dilps to control growth and metabolism.

Tacrolimus modulates the PI3K AKT mTOR pathway in retinal epithelial cells under inflammatory stress

Droughts with no agro-climatological extremes

Invasin-functionalized PIC hydrogels enable long-term 3D culture of epithelial organoids

Tissue stem cell (TSC)-derived epithelial organoids are typically cultured in Matrigel [T. Sato et al. , Nature 459 , 262–265 (2009)], an extracellular matrix-like hydrogel produced from Engelbreth–Holm–Swarm sarcoma cells. This tumor is grown in the mouse abdomen [R. W. Orkin et al. , J. Exp. Med. 145 , 204–220 (1977)]. Previously, we demonstrated that the Yersinia membrane protein Invasin, coated on transwells, replaces Matrigel by activating β1-integrins, allowing long-term expansion of primary epithelial cells as 2D organoid sheets [J. J. A. P. M. Wijnakker et al. , Proc. Natl. Acad. Sci. U.S.A. 122 , e2420595121 (2025)]. Here, we functionalize a synthetic polyisocyanide (PIC) hydrogel with the integrin-activating domain of Invasin (INV). PIC hydrogels are soluble at 4 °C and form a gel at 37 °C [P. H. J. Kouwer et al. , Nature 493 , 651–655 (2013)]. When INV is covalently linked to PIC, the resulting hydrogel supports multipassage 3D growth of human intestinal and airway organoids. Self-renewal, polarization, and differentiation are maintained. The 3D swelling assay for cystic fibrosis drug testing (S. F. Boj et al. , J. Vis. Exp. (2017), 10.3791/55159] was validated using PIC-INV. With PIC-INV hydrogels, we establish a fully defined and animal-free system for 3D TSC-derived organoid culture.

A novel combination model for ultra-short-term wind speed prediction

Fine-scale mapping of irrigation suitability in South Africa using ensemble modelling

Abstract Food insecurity, exacerbated by a growing population and environmental change, poses a significant challenge in Southern Africa. Enhancing agricultural productivity through efficient irrigation practices is crucial for achieving food and water security and sustainable development goals. This study applied an ensemble modelling approach to identify and assess irrigation suitability areas across South Africa, combining the predictive power of Random Forest, Extreme Gradient Boosting (XGBoost), and Gradient Boosting Machine (GBM) algorithms. These machine learning models were applied using cropland presence/pseudo-absence data and a suite of predictor variables. The ensemble model, leveraging a weighted averaging approach based on individual model performance, outperformed the individual models, achieving a TSS of 0.66 and an AUC of 0.90. Land use, population density, and elevation were identified as key factors determining irrigation suitability. The ensemble model also revealed substantial spatial variation in irrigation potential across South Africa, with the Northern Cape and Western Cape provinces exhibiting the largest suitable areas. The results provide critical information for targeted irrigation development, enabling efficient resource allocation, and maximising agricultural productivity. This data-driven approach offers a robust framework for sustainable agrarian planning in the face of increasing food demands and climate change, contributing to enhanced food security and economic development in South Africa.

Identification of CCR4C as a chloroplast-localized NADP(H) phosphatase regulating NAD(P)(H) balance in <i>Arabidopsis</i>

NAD(P)(H) metabolism plays a crucial role in plant development and growth. NADK2, a chloroplast-localized NAD kinase, supplies NADP + to the photosynthetic electron transport chain. The Arabidopsis T-DNA insertion mutant of NADK2 ( nadk2 ) exhibits a reduced NADP + /NAD + ratio, slow growth, and pale green leaves. To gain further insights into NAD(P)(H) metabolism in chloroplasts, nadk2 revertant mutants ( nkr ) were screened from the M2 generation of EMS (ethyl methane sulfonate)-treated nadk2 seeds. Among them, nkr1 displayed greener leaves and improved growth compared to nadk2 . Genetic mapping and genomic sequencing identified At3g18500 ( CCR4C ) as the causal gene. The nkr1 mutant carried a single nucleotide substitution, introducing a stop codon within the predicted N-terminal chloroplast localization signal, resulting in the loss of CCR4C protein function. The nadk2 ccr4c double mutant restored leaf color and growth to near wild-type levels. To investigate the function of CCR4C, recombinant CCR4C protein was purified and shown to directly convert NADP(H) to NAD(H). Localization analysis with CCR4C-GFP fusion proteins confirmed chloroplast targeting. Furthermore, ccr4c single mutants exhibited disrupted NAD(P)(H) balance and enhanced tolerance to ROS stress (e.g., H 2 O 2 , methyl viologen). These findings reveal CCR4C as a chloroplast-localized NADP(H) phosphatase crucial for maintaining NAD(P)(H) balance, providing insights into how plant cells manage chloroplast metabolism.

The sperm quality change in 6 months recovery from COVID-19: a retrospective observational study

Comparative study of thermal response for tetra nanofluid through a vertically oriented needle device inspired by combined convection and porous media

Correction for Garzon et al., MicroRNA fingerprints during human megakaryocytopoiesis

Effect of the intravenous acetaminophen clinical pathway on postoperative analgesia in spinal fusion surgery

Synthesis of Al2O3-Reinforced SrO–SiO2–K2O glasses with enhanced optical, and biological properties for biomedical applications

Safety versus performance: How multi-objective learning reduces barriers to market entry

Emerging marketplaces for large language models and other large-scale machine learning models appear to exhibit market concentration, which has raised concerns about whether there are insurmountable barriers to entry in such markets. In this work, we study this issue from both an economic and an algorithmic point of view, focusing on a phenomenon that reduces barriers to entry. Specifically, an incumbent company risks reputational damage unless its model is sufficiently aligned with safety objectives, whereas a new company can more easily avoid reputational damage. To study this issue formally, we define a multi-objective high-dimensional regression framework that captures reputational damage, and we characterize the number of data points that a new company needs to enter the market. Our results demonstrate how multi-objective considerations can fundamentally reduce barriers to entry—the required number of data points can be significantly smaller than the incumbent company’s dataset size. En route to proving these results, we develop scaling laws for high-dimensional linear regression in multi-objective environments, showing that the scaling rate becomes slower when the dataset size is large, which could be of independent interest.

Implantation of a vascular access button in mice

Abstract Vascular access presents unique challenges in experimental mice due to their small size and anatomical constraints. Achieving reliable vascular access is crucial for optimizing experimental outcomes, especially in protocols requiring serial blood sampling or repeated intravascular therapy. Although vascular access buttons (VABs) offer significant advantages, their widespread adoption has been limited by technical challenges and a lack of comprehensive validation regarding their safety, feasibility, and long-term management. To address these gaps, we conducted a comprehensive evaluation of VAB implantation in mice. The technical success rate was 90.2%, and the 28-day survival rate was 80.4%. Optimal catheter insertion lengths determined by intraoperative and autopsy findings, and computed tomography were 9.5 ± 0.6 mm (20–25 g), 10.1 ± 0.8 mm (25–30 g), and 11.2 ± 0.5 mm (&gt; 30 g), respectively. Catheter patency was analyzed by stratifying the cohort into groups based on physical parameters such as catheter tip geometry, heparin concentration in the maintenance solution, and frequency of catheter maintenance procedures. Although approximately half of the mice lost complete catheter patency by day 14, the majority maintained partial patency at day 28 in all experimental groups except for two cases of complete occlusion in the 2 Fr square tip, low-dose heparin, weekly maintenance group. The evaluation of biodistribution and clearance with indocyanine green indicated that VAB administration may have advantages over conventional venipuncture. These standardized methodologies can provide a framework for diverse biomedical research applications, enhancing both the efficiency and reproducibility of studies requiring reliable vascular access.

Predictive value of PD-1+CD3+ T cells for 30-day mortality in patients with sepsis

Emergence of antiphage functions from random sequence libraries reveals mechanisms of gene birth

De novo gene birth—the emergence of genes from nongenic sequences—drives biological innovation, yet its adaptive potential remains poorly understood. To investigate this issue, we screened libraries of ~100 million short (semi-)random sequences, mimicking early stages of gene birth, for genes that promote Escherichia coli survival during phage infection. This selection uncovered thousands of functional genes that confer viral resistance through at least two distinct mechanisms: 1) activation of a bacterial regulatory system that remodels the outer membrane, which provides broad-spectrum defense, and 2) transcriptional repression of bacterial outer membrane receptors required for phage adsorption, which provides phage-specific protection. Remarkably, unrelated random genes with no sequence similarity produced similar protective phenotypes, revealing that diverse sequences can converge on equivalent functions. We further showed that T4 phage rapidly evolves to counter these novel defenses, acquiring baseplate mutations that enhance adsorption to resistant hosts. Together, these findings demonstrate that random sequences can rapidly evolve into functional genes with direct fitness benefit, highlighting the evolutionary potential of de novo gene birth in the microbial world.

Exploring community pharmacy professionals’ knowledge, attitudes, and practices toward medication therapy management in Southwest Ethiopia: a cross-sectional study

Optimal probability function for ultimate resistance of offshore T/Y-connections enhanced with collar plates under compression, tension, and bending loads

Iron limitation differentially affects viral replication in key marine microbes

Viral lysis accounts for much of microbial mortality in the ocean, and iron (Fe) is a critical micronutrient that can limit phytoplankton growth. However, interactions between Fe nutrition of microbes, including both heterotrophic bacteria and phytoplankton, and viral lysis are not well known. Here, we present viral infection dynamics under Fe-limited and Fe-replete conditions for isolates of three types of marine picoplankton, the photosynthetic picoeukaryote Ostreococcus , the cyanobacterium Synechococcus , and the heterotrophic bacterium Vibrio . Iron limitation of Ostreococcus resulted in slowed growth and reduced viral burst sizes; this is similar to prior results from studies of larger eukaryotic phytoplankton, where reduced viral replication under Fe limitation is attributed to the viral reliance on host metabolism and replication machinery. Fe limitation of one Vibrio impacted dynamics of its virus similarly, lengthening the latent period before infected cells burst to release new viruses, and reducing the number of infective particles released upon lysis. In contrast, for another Vibrio isolate, Fe limitation had no discernible effect on replication of its virus. Furthermore, dynamics of three cyanophages that infect the same Synechococcus isolate were not affected by Fe limitation of the host, either in terms of latent period or burst size. The results show that some marine viruses, particularly cyanophages, can replicate efficiently even when host growth is compromised. These findings have implications for marine ecology and carbon cycling in Fe-limited regions of the global ocean.