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Functional protein design and enhancement with ontology reinforcement iteration
CD99-targeted immunomagnetic negative selection: A novel strategy for high-purity pancreatic islet isolation in murine models
Background Islet transplantation represents a promising therapeutic approach for type 1 diabetes through restoration of endogenous insulin production. However, efficient purification of islets from surrounding exocrine tissue remains a critical challenge, as current methodologies often compromise purity, yield, or islet viability. Methods We exploited the differential expression of CD99 between murine pancreatic exocrine tissue (high expression) and islets (negligible expression) to develop a novel immunomagnetic negative selection protocol. Expression patterns were validated using immunofluorescence, immunohistochemistry, and western blot. Subsequently, streptavidin-conjugated magnetic beads coupled with biotinylated anti-CD99 antibodies were employed to selectively deplete CD99-positive exocrine cells from pancreatic digests, thereby enriching viable islets. Results This approach achieved a remarkable increase in islet purity from 10.4 ± 3.9% to 93.0 ± 1.4% ( P < 0.0001). Purified islets maintained structural integrity and demonstrated robust glucose-stimulated insulin secretion in vitro , comparable to islets isolated via conventional Ficoll density gradient centrifugation ( P > 0.05). In a syngeneic transplantation model, 400 islet equivalents effectively reversed streptozotocin-induced diabetes, with therapeutic efficacy equivalent to Ficoll-purified islets ( P > 0.05). Conclusions Our CD99-targeted immunomagnetic negative selection offers a novel, highly specific, and effective alternative for obtaining high-quality islets, as demonstrated by their excellent functional performance both in vitro and in vivo .
Why the crisis in official statistics matters — and how it can be fixed
Pyrometallurgical valorization of waelz, fayalite, and linz-donawitz slag mixtures
Abstract Waelz, Linz-Donawitz, and Fayalite slags are one of the largest industrial byproducts. They are presently under-utilized, and ending up in landfill. This work demonstrates that mixtures of these slags can be directly valorized, given that the combined composition has basicity (CaO/SiO₂ = 0.9–1.0) without the addition of fresh fluxes. Furthermore, the current work contributes to a deeper understanding of slag behavior by linking basicity and viscosity to interfacial tension and by constructing an isoviscosity-ternary phase diagram of CaO-SiO 2 -Al 2 O 3 . The current methodology gives a more comprehensive approach for designing self-fluxing slag mixtures that is feasible for smelting. X-ray computed tomography (XCT) measurements of the smelted products show the internal micro-structure, which provided insights into the correlations between viscosity, interfacial-tension, and the performance of each mixture. The metal product qualifies as vanadium-bearing pig iron based on the elemental analysis while the slag met the criteria for non-hazardous, construction-grade material according to the specifications of the United States, United Kingdom and Germany. Additionally, the roasted slag contains phases suitable for ceramic and porcelain applications, broadening its commercial application. The study illustrates a practical implementation of circular-economy principles for the metal industry and for metallurgical waste management by demonstrating electrified pyrometallurgy based on the induction furnace.
Subgroup performance of a commercial digital breast tomosynthesis model for breast cancer detection
Characterization of a unique phosphopantetheinyl transferase (PPTase) in the fish pathogen Pseudomonas plecoglossicida
Phosphopantetheinyl transferase (PPTase) is a key enzyme that catalyzes 4’-phosphopantetheinylation at conserved serine residues of fatty acid synthases, polyketide synthases, and nonribosomal peptide synthetases. It is involved in the biosynthesis of primary and secondary metabolites and has been well characterized as an important virulence factor in many pathogenic microorganisms. A unique Sfp-type PPTase was annotated in Pseudomonas plecoglossicida NB2011, the causative agent of visceral granulomas syndrome in the large yellow croaker ( Larimichthys crocea ). However, the biological function and virulence significance of this enzyme in the pathogen have not yet been studied. In this paper, we aligned the target sequence with other Sfp-type PPTases, constructed a deletion mutant using the method of double homologous recombination, investigated the biological phenotypes, and compared the intracellular survival and virulence of the mutant and wild-type strains. Additionally, we performed RNA-seq and analyzed the transcription data. The results indicated that the PPTase of P. plecoglossicida shares the highest sequence similarity with PapcpS of P. aeruginosa . A conditional mutant was successfully constructed when pET22b-entD was present. Compared to the wild-type strain, the mutant was lysine indispensable, exhibited poorer growth during the late log phase, was more sensitive to H 2 O 2 exposure, displayed lower siderophore activity, and exhibited a significant reduction in total fatty acid synthesis. Furthermore, fewer bacterial cells of the mutant persisted in mouse macrophage J774A.1, and its toxicity to the host fish was substantially attenuated. RNA-seq analysis revealed 179 differentially expressed genes (DEGs), including 105 up-regulated and 74 down-regulated genes. Genes involved in iron transportation, oxidative stress response, and ABC transporters were down-regulated, while genes in the type III and type VI secretion systems were predominantly up-regulated. The transcriptomic results are consistent with the phenotypic observations, suggesting that the PPTase is essential for bacterial survival and plays important roles in the pathogenicity process. This is the first paper on the PPTase from P. plecoglossicida .
Autism in older adults: the health system must recognize its effects
Glutamine promotes acute wound healing by mediating glutamine metabolism and M2 macrophage polarization via the MEK/ERK/SLC1A5 signaling pathway
Engineering synthetic cells with intramembrane domains possessing distinct bilayer asymmetries
Abstract Our understanding of how membrane asymmetry governs biological function is limited by the lack of techniques to produce model membranes which can reliably and accurately mimic cellular membrane asymmetry. Not only in terms of asymmetric lipid distribution, but also how that asymmetry can be confined to specific lateral locations across the membrane. Here we present an inverted emulsion method that can be used to produce synthetic cells with symmetric and asymmetric bilayers, as well as phase separation where the intermembrane domains possess distinct bilayer asymmetries. We assess the degree of lipid asymmetry using protein-lipid interaction and quenching assays. Surprisingly, the synthetic cells with asymmetric and phase separated membranes displayed pronounced curvature of the domains and resulted in membrane budding and division. Overall, this work develops biomimetic membranes with lipid compositions akin to natural biomembranes – an essential element in the development of functional synthetic cells.
Predicting oil contamination in water using machine learning on microbial compositions
We present a compact and generative machine-learning framework that predicts oil contamination based on microbial community compositions from experimental samples. Our method combines dimensionality reduction with data augmentation and generative modeling to address high-dimensional, non-linear, and sparse microbial data. To reduce the 503-dimensional bacterial composition dataset, we compared three dimensionality reduction techniques: feature importance from random forest, principal component analysis (PCA), and t-distributed stochastic neighbor embedding (t-SNE). Feature importance outperformed PCA and t-SNE, improving predictive performance and identifying microbial species most strongly correlated with oil contamination. To mitigate data scarcity, we augmented the training data using an augmented data neural network (ADNN) with noise injection. Samples generated by a variational autoencoder (VAE) were used as controlled perturbations to probe model robustness during stress testing. Using the top 3–10 bacterial features, our model achieved an R² value of up to 0.99 in both training and stress testing for predicting oil contamination from microbial data. In a bottle-level hold-out evaluation (22 splits at an 80/20 bottle ratio), performance on held-out bottles was lower and variable (mean test R² = −0.150), indicating limited generalization within this cohort. These results should be interpreted as a feasibility demonstration requiring validation on larger independent datasets.
How wealthy tech entrepreneurs seek to shape politics, culture and the future — and why we must resist
Identification and evaluation of tumor pyroptosis-associated antigens for design a vaccine candidate against lung cancer
Abstract Lung cancer is the leading cause of cancer-related mortality worldwide, emphasizing the need for innovative therapeutic strategies. This study utilized immunoinformatics and structural bioinformatics approaches to design and evaluate a multi-epitope vaccine targeting pyroptosis-associated antigens (CARD8, NAIP, NLRP1, and NLRP3), which are implicated in lung cancer immunology. Fifteen T-cell and B-cell epitopes were identified, analyzed for their antigenicity, non-toxicity, non-allergenicity, and immune-stimulatory potential, and optimized to construct a vaccine with suitable adjuvants and linkers. The vaccine demonstrated high antigenicity, solubility, and stability, as validated through physicochemical analyses. Its three-dimensional structure was modeled, refined, and validated using molecular modeling approaches. Molecular docking studies revealed stable and strong interactions between the vaccine and key immune receptors (TLR2, TLR4, TLR5, TLR3, TLR7, and TLR8), indicating its potential to activate both innate and adaptive immunity. Molecular dynamics simulations confirmed the vaccine’s structural stability and solvent accessibility over 100 ns across ten replicas. Immune simulations demonstrated strong immunogenic responses, including elevated antibody titers, memory cell populations, and cytokine production. Codon optimization and in silico cloning further ensured efficient expression in Escherichia coli , facilitating experimental application. These findings underscore the vaccine’s promise as a therapeutic candidate against lung cancer, warranting further in vitro and in vivo investigations.
Genomic inference of sites of transmission during regional spread of blaNDM Klebsiella pneumoniae in Michigan
Association between sleep duration and chronic lung diseases among Chinese middle-aged and older adults: A cross-sectional study
Background Chronic lung diseases (CLDs) continue to be a major global public health concern. Previous studies have produced inconsistent findings regarding the relationship between sleep duration and CLDs. This study aimed to examine the association between sleep duration and CLDs in Chinese middle-aged and elderly adults. Methods This cross-sectional study used data from the 2011 survey of the China Health and Retirement Longitudinal Study (CHARLS). Self-reported sleep duration was collected using a structured questionnaire, and CLDs was defined by self-reported physician diagnosis. Multiple logistic regression models were employed to examine the association between sleep duration and CLDs. We used generalized additive model and smoothing fitted curves to examine whether nonlinear relationship existed. Results A total of 13,759 participants were included. Among participants, 5,773 (42.0%) slept less than 7 hours, 4,711 (34.2%) slept between 7–8 hours, and 3,275 (23.8%) slept more than 8 hours. After adjusting for all covariates, logistic regression showed a positive association between short sleep duration (< 7 hours) and CLDs (OR 1.29, 95% CI 1.10–1.52) compared to the normal group (7–8 hours). In addition, smoothing fitted curves indicated the existence of a non-linear association between sleep duration and CLDs. Conclusions Short sleep duration was associated with a higher likelihood of CLDs in Chinese middle-aged and elderly population. Further investigations are warranted to test this association.
AI is programmed to hijack human empathy — we must resist that
A robust mouse liver organoid platform enables sustained multicellular maturation and fibrosis modeling from a single tissue sample
Abstract Efficient isolation and culture of liver organoids are critical for studying liver fibrosis, liver regeneration and drug toxicity and screening. However, preserving mature hepatobiliary characteristics and concurrently incorporating fibrosis-producing hepatic stellate cells (HSCs) remains a significant challenge, often hindering the large-scale production of organoids capable of replicating key liver functions. Here, we report a robust 3D organoid culture system that enables simultaneous isolation and long-term propagation of primary hepatocytes, cholangiocytes, and HSCs from a single source of mouse liver tissue. By supplementing the Hep-Med with Notch signaling inhibitor and dexamethasone, we achieved sustained organoid maturity, including stable albumin production, metabolic activity, and liver-specific gene expression, over multiple passages in culture. Quiescent HSCs within the system retained lipid droplets and could be activated into a myofibroblast-like phenotype, also called activated HSCs, via TGFβ stimulation. Activated HSCs impaired the proliferation and stemness, and induced epithelial-mesenchymal transition (EMT) of Hep-Orgs and Cho-Orgs, enabling in vitro liver fibrosis modeling. Optimized for minimal tissue input, this platform maximizes tissue utilization efficiency while preserving the liver’s heterogeneous cellular architecture. Its versatility supports diverse applications in liver disease modeling, drug discovery, and regenerative medicine.
CD177⁺ neutrophil-platelet aggregates contribute to thromboinflammation via NETs in necrotizing enterocolitis
The relationship between intellectual curiosity and adolescents’ mathematical problem-solving ability: A moderated mediation model
The ability to solve mathematical problems is one of the key skills for students to excel in mathematics. Based on PISA 2022 data from Ireland (N = 5,521), the current study constructed a moderated mediation model to systematically examine how intellectual curiosity (IC) influences mathematical problem-solving ability (MPSA) through the mediation of self-efficacy (SE), and to test the moderating role of perseverance (PE). The results indicated significant positive correlations among IC, SE, PE, and MPSA. Further mediation analysis revealed that IC not only exerted a direct effect on MPSA, but also affected MPSA indirectly through the role of SE, accounting for 45.40% of the total effect. Moreover, the moderated mediation analysis uncovered a dual role of PE in the mechanism through which IC influences MPSA: it negatively moderated the paths from IC to SE and from IC to MPSA, while positively moderating the path from SE to MPSA. Multi-group analysis revealed significant heterogeneity in the mechanism across gender and economic, social, and cultural status (ESCS). Specifically, male students relied more heavily on the mediating path of SE, whereas female students exhibited a stronger direct effect of IC. Students with low ESCS primarily depended on the direct drive of IC, whereas their high-ESCS counterparts achieved ability enhancement more through the mediating pathway of SE. These findings elucidate the cross-group psychological mechanisms influencing MPSA, validate the applicability of self-determination theory and social cognitive theory in standardized educational contexts, provide empirical evidence for Ireland to formulate differentiated and targeted mathematics education intervention policies, and offer practical insights for promoting the comprehensive development of adolescents.
Synthesis of rare earth doped MoS2 by the co-pyrolysis of molecular precursors
Abstract The synthesis of Er- and Nd-doped MoS 2 powders by the co-pyrolysis of molecular precursors is demonstrated by heating tetrakis- (diethyldithiocarbamato) molybdenum(IV) (Mo(DTC) 4 ) and mono- 1,10-phenanthroline tris -(diethyl dithiocarbamato) erbium(III) or mono- 1,10-phenanthroline tris -(diethyl dithiocarbamato) neodymium(III) (Ln(DTC) 3 phen, where Ln = Er, Nd) to 500 °C for 1 h. Powder x-ray diffraction and Raman spectroscopy indicated that the resulting powders produced from this reaction are comprised of 0D nanoscale crystallites of the 2 H phase of MoS 2 . Spatial mapping of elements in these samples was performed in the scanning electron microscope at the microscale using energy dispersive X-ray spectroscopic mapping, which showed that the dopants are homogeneously distributed throughout the samples. Synchrotron radiation x-ray absorption measurements tentatively indicate that the dopants are incorporated within the MoS 2 layers rather than being intercalated between them. Electron paramagnetic resonance spectroscopy and SQUID magnetometry demonstrated that rare earth doping of MoS 2 significantly enhances the magnetic response of the material. Remarkably, the samples are found to remain paramagnetic down to temperature at least as low as 2 K.