Search Results (3,259)

Wide-bandgap (WBG) perovskite solar cells (PSCs) are critical for high-efficiency tandem photovoltaic devices, but their practical application is severely limited by phase separation and poor film quality. To address these challenges, this study proposes a dual-additive passivation strategy using potassium thiocyanate (KSCN) and potassium chloride (KCl) to synergistically optimize the crystallinity and defect state of WBG perovskite films. The selection of KSCN/KCl is based on their complementary functionalities: K⁺ ions occupy lattice vacancies to suppress ion migration, Cl⁻ ions promote oriented crystal growth, and SCN⁻ ions passivate surface defects via Lewis acid-base interactions. A series of KSCN/KCl concentrations (relative to Pb) were tested, and the effects of dual additives on film properties and device performance were systematically characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), photoluminescence (PL), space-charge-limited current (SCLC), current-voltage (J-V), and external quantum efficiency (EQE) measurements. Results show that the dual additives significantly enhance film crystallinity (average grain size increased by 27.0% vs. control), reduce surface roughness (from 86.50 nm to 24.06 nm), and passivate defects-suppressing non-radiative recombination and increasing electrical conductivity. For WBG PSCs, the champion device with KSCN (0.5 mol%) + KCl (1 mol%) exhibits a power conversion efficiency (PCE) of 16.85%, representing a 19.4% improvement over the control (14.11%), along with enhanced open-circuit voltage (Voc: +2.8%), short-circuit current density (Jsc: +6.7%), and fill factor (FF: +8.9%). Maximum power point (MPP) tracking confirms superior operational stability under illumination. This dual-inorganic-additive strategy provides a generalizable approach for the rational design of stable, high-efficiency WBG perovskite films. Full article

Three-dimensional (3D) hepatic tissue engineering holds great potential for liver regeneration, disease modeling, and drug screening. These applications require densely layered hepatic tissues that mimic native 3D liver architecture. However, limited oxygen supply and reduced cell viability in densely layered hepatic constructs remain key challenges. To overcome this, this study developed a photo-crosslinkable, oxygen-releasing hydrogel composed of methacrylated hyaluronic acid (MeHA) and calcium peroxide (CPO). The MeHA/CPO hydrogel exhibited favorable rheological properties and sustained oxygen release. Induced pluripotent stem cell-derived hepatocyte (iHep) sheets were cultured with or without MeHA/CPO hydrogel in single- and double-layer formats. The hydrogel enhanced structural integrity and supported the formation of a multilayer (~33 µm). Double-layered iHep sheets with MeHA/CPO showed the significantly increased expression of paracrine factors (HGF, VEGF, Alb) and improved albumin secretion without loss of hepatocyte identity (AFP, HNF4α). This oxygen-releasing system effectively alleviates hypoxic stress, supporting the structural and functional viability of multilayered iHep sheets. Our platform provides a promising approach for engineering metabolically active hepatic tissues and may serve as a foundation for 3D hepatic tissue engineering. Full article

Human induced pluripotent cells (hiPSCs), generated in vitro, represent a groundbreaking tool for tissue regeneration and repair. Understanding the metabolic intricacies governing hiPSCs is crucial for optimizing their performance across diverse environmental conditions and improving production strategies. To this end, in this work, we introduce hiPSCGEM01, the first genome-scale, context-specific metabolic model (GEM) uniquely tailored to fibroblast-derived hiPSCs, marking a clear distinction from existing models of embryonic and cancer stem cells. hiPSCGEM01 was developed using relevant genome expression data carefully selected from the Gene Expression Omnibus (GEO), and integrated with the RECON 3D framework, a comprehensive genome-scale metabolic model of human metabolism. Redundant and unused reactions and genes were identified and removed from the model. Key reactions, including those facilitating the exchange and transport of metabolites between extracellular and intracellular environments, along with all metabolites required to simulate the growth medium, were integrated into hiPSCGEM01. Finally, blocked reactions and dead-end metabolites were identified and adequately solved. Knockout simulations combined with flux balance analysis (FBA) were employed to identify essential genes and metabolites within the metabolic network, providing a comprehensive systems-level view of fibroblast-derived hiPSC metabolism. Notably, the model uncovered the unexpected involvement of nitrate and xenobiotic metabolism—pathways not previously associated with hiPSCs—highlighting potential novel mechanisms of cellular adaptation that merit further investigation. hiPSCGEM01 establishes a robust platform for in silico analysis and the rational optimization of in vitro experiments. Future applications include the evaluation and refinement of culture media, the design of new formulations, and the prediction of hiPSC responses under varying growth conditions, ultimately advancing both experimental and clinical outcomes. Full article

Background: In recent decades, malaria vector species distribution and insecticide resistance have taken new colonization steps across Africa. Understanding the malaria vector insecticide resistance status, blood meal source, and species composition is of paramount importance in designing evidence-based vector control strategies. This study assessed the blood meal sources, sporozoite (infectivity) rate, and knockdown resistance allele’s frequency in female Anopheles arabiensis in chosen villages of Jabi Tehnan District, Northwest Ethiopia. Methods: The host-seeking and resting Anopheles gambiae s.l. were collected using human landing catches (HLCs), CDC light traps (CDC-LTs), pyrethrum spray catches (PSCs), and pit shelters (PSs) both indoors and outdoors. The analysis of both blood meal sources and circumsporozoite proteins was performed using enzyme-linked immunosorbent assay (ELISA). The detection of knockdown resistance gene mutations and species identification were conducted using a polymerase chain reaction (PCR). Results: A total of 5098 female Anopheles gambiae s.l. were collected. Of these, 1690 (33.2%) were collected from HLCs, 1423 (27.9%) from CDC light traps, 1635 (32.0%) from PSCs, and only 350 (6.9%) from pit shelters (PSs). Of these, 57.2% (n = 2915) female Anopheles mosquitoes were collected indoors using CDC light traps (CDC-LTs), human landing catches (HLCs), and pyrethrum spray catches (PSCs), while 38.2% (n = 2183) were collected outdoors using human landing collection (HLC), CDC light traps (CDC-LTs), and artificial pit shelters (PSs). Molecular identification to the species level showed that among the 530 An. gambiae s.l. samples analyzed using PCR, 96.03% (509) were An. arabiensis, and 3.97% (21) were unidentified species. The biting peak was found to be from 22:00 to 00:00 h for An. arabiensis. However, their activity decreased sharply after 23:00 to 00:00 h. The distribution of knockdown resistance genes in the tested specimens of An. arabiensis consisted of 1.4% (n = 3) heterozygous resistant (RS), 17.9% (n = 38) homozygous resistant (RR), and 80.7% (n = 171) homozygous susceptible (SS) genotypes. A higher proportion of Anopheles mosquitoes analyzed for blood meal analysis had a human blood meal origin at 13.1% (n = 47), followed by bovine at 8.9% (n = 32) and mixed at 5.8% (n = 21). Conclusions: The dominant malaria vector species was Anopheles arabiensis in the study area with a higher human blood meal origin. The Kdr gene was confirmed in the tested An. arabiensis, indicating that an alternative insecticide class should be used in the study area. Full article

Pluripotent stem cells (PSCs) exhibit remarkable self-renewal capacity and differentiation potential, necessitating tight regulation of gene expression at both transcriptional and post-transcriptional levels. Among post-transcriptional mechanisms, RNA turnover and degradation together play pivotal roles in maintaining transcriptome homeostasis and controlling RNA stability. RNA degradation plays a pivotal role in determining transcript stability for both messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs), thereby influencing cell identity and fate transitions. The core RNA decay machinery, which includes exonucleases, decapping complexes, RNA helicases, and the RNA exosome, ensures timely and selective decay of transcripts. In addition, RNA modifications such as 5′ capping and N6-methyladenosine (m⁶A) further modulate RNA stability, contributing to the fine-tuning of gene regulatory networks essential for maintaining PSC states. Recent single-cell and multi-omics studies have revealed that RNA degradation exhibits heterogeneous and dynamic kinetics during cell fate transitions, highlighting its role in preserving transcriptome homeostasis. Conversely, disruption of RNA decay pathways has been implicated in developmental defects and disease, underscoring their potential as therapeutic targets. Collectively, RNA degradation emerges as a central regulator of PSC biology, integrating the decay of both mRNAs and ncRNAs to orchestrate pluripotency maintenance, lineage commitment, and disease susceptibility. Full article

Background: Primary sclerosing cholangitis (PSC) is a rare chronic liver disease characterised by bile duct strictures. Magnetic resonance cholangiopancreatography (MRCP) is the principal imaging modality for diagnosis; however, its interpretation is subjective. Quantitative MRCP (MRCP+) provides quantitative assessment of the biliary anatomy and can support objective disease assessment. We evaluated the potential impact, feasibility, and perceived usefulness that MRCP+ would have on PSC patient management. Methods: Alongside systematic evaluation of UK and European clinical guidelines on PSC management, semi-structured interviews with 16 stakeholders were conducted. The Lean Assessment Process methodology was used to assess potential impact and feasibility of adopting MRCP+ for the PSC care pathway within the NHS. Price as a barrier to adoption was investigated to evaluate perceptions between technology cost and adoption. Perceived ease of use and perceived trust were calculated and used to evaluate perceived usefulness (PU). Results: For PSC management, MRCP (81%) scored higher than liver biopsy (68%) and ERCP (50%) due to its non-invasive nature. There was good internal consistency between responders on the relationship between price point and the use of MRCP+ to support diagnosis (CA:0.836) and monitoring (CA:0.904). A price point of up to GBP 500 was unlikely to be a barrier for adoption. The overall perceived usefulness for MRCP+ for patient management was 74%. Conclusions: There is strong interest in using MRCP+ to support PSC management. MRCP+ has the potential to address unmet needs including reducing subjectivity, measurement of the whole biliary tree and objectively measuring biliary disease progression. Full article

High variability in stem cell research is a well-known limiting phenomenon, with technical variation across experiments and laboratories often surpassing variation caused by genotypic effects of induced pluripotent stem cell (iPSC) lines. Evaluation of kidney organoid protocols and culture conditions across laboratories remains scarce in the literature. We used the original air-medium interface protocol to evaluate kidney organoid success rate and reproducibility with several human iPSC lines, including a novel patient-derived GRACILE syndrome iPSC line. Organoid morphology was assessed with light microscopy and immunofluorescence-stained maturing glomerular and tubular structures. The protocol was further adapted to four microplate-based high-throughput approaches utilizing spheroid culture steps. Quantitative high-content screening analysis of the nephrin-positive podocytes and ECAD-positive tubular cells revealed that the choice of approach and culture conditions were significantly associated with structure development. The culture approach, iPSC line, experimental replication, and initial cell number explained 35–77% of the variability in the logit-transformed proportion of nephrin and ECAD-positive area, when fitted into multiple linear models. Our study highlights the benefits of high-throughput culture and multivariate techniques to better distinguish sources of technical and biological variation in morphological analysis of organoids. Our microplate-based high-throughput approach is easily adaptable for other laboratories to combat organoid size variability. Full article

CWD surveillance and diagnosis are important issues in Europe since its detection in Norway, as some of its strains, like that of classical scrapie, are contagious. In addition, there are concerns as several matters about CWD are not yet known. Although diagnostic methods for the active surveillance in bovine and small ruminants have been able to detect the European CWD strains, a retrospective study on Italian wild red deer (Cervus elaphus) samples was performed to compare the results obtained from rapid screening tests, authorized according to EU Regulation 999/2001, and the RT-QuIC, a highly sensitive method in the detection of prion disease infection. A total of one hundred brainstems and medial retropharyngeal lymph nodes were selected out of those received from the CWD Italian surveillance system. Confirmed CWD-positive and -negative samples were included in the study as controls. All of the samples were first tested with the HerdChek BSE–Scrapie Antigen Test and then using the RT-QuIC. The rapid test was negative in all brainstem and lymph node samples. RT-QuIC analyses showed only one red deer brainstem sample positive for seeding activity, while all lymph nodes were negative, including the one from this case. This positive brainstem sample was then re-extracted and retested using two different recombinant prion protein substrates (Ha90-231; BV23-231) and their different batches from the first analyses. Seeding activity was consistently confirmed across both substrates and extractions, with positive signals detected down to dilutions of 10⁻⁴ using rPrP Ha90-231 and as low as 10⁻⁶ with rPrP BV23-231. The additional diagnostic investigations performed on this red deer using the alternative rapid test (TeSeE SAP Combi), Western blot, and immunohistochemistry showed negative results both in the brainstem and lymph nodes. This study showed that overall, the results obtained with the HerdChek BSE–Scrapie Antigen Test and RT-QuIC agree except in one case. Our findings highlight the potential of the RT-QuIC method to detect very low levels of PrP^Sc-associated seeding activity that may escape detection using classical methods. While seeding activity does not always equate to infectivity, only a bioassay will confirm the real disease status of this Italian case. These findings support the integration of RT-QuIC as a powerful complementary tool within existing surveillance frameworks to strengthen early detection and diagnostic accuracy. Full article

Human early embryogenesis remains unexplored due to limited access to human embryos for research purposes. Meanwhile, the number of natural early pregnancy terminations remains significant, and solving the problem requires a deep understanding of the developmental mechanisms of this period. Although assisted reproductive technologies (ART) utilize up-to-date approaches in culturing human embryos in vitro, characterization of the embryos is still based on visual evaluation and subjective assessment. In addition, embryonic development in animal models, such as rodents and cattle, correlates poorly with human embryonic development. Synthetic embryology presents a promising new approach for studying human embryos involving the creation of embryos without the use of haploid germ cells. Instead, diploid pluripotent stem cells (PSCs) in a given state of pluripotency, which is maintained under conditions of induction and/or inhibition of certain signaling pathways, are used. Synthetic embryo systems (SES) may become a successful alternative model for studying fundamental processes of human early preimplantation embryogenesis, exploring new methods of objective embryo qualification, and personalized approaches in ART. However, the question of whether SES models can be considered as full-fledged mimics of the embryo remains open. This review examines human blastocyst-like structures known as blastoids. It discusses their use as models, as well as the parameters that need to be modified to more accurately simulate the human blastocyst. Full article

Cell-based therapeutics are redefining interventions for vision loss by enabling tissue replacement, regeneration, and neuroprotection. This review surveys contemporary cellular strategies in ophthalmology through the lenses of therapeutic effectiveness, translational readiness, and governance. We profile principal sources—embryonic and induced pluripotent stem cells, mesenchymal stromal cells, retinal pigment epithelium, retinal progenitor and limbal stem cells—and enabling platforms including extracellular vesicles, encapsulated cell technology and biomaterial scaffolds. We synthesize clinical evidence across age-related macular degeneration, inherited retinal dystrophies, and corneal injury/limbal stem-cell deficiency, and highlight emerging applications for glaucoma and diabetic retinopathy. Delivery routes (subretinal, intravitreal, anterior segment) and graft formats (single cells, sheets/patches, organoids) are compared using standardized structural and functional endpoints. Persistent barriers include GMP-compliant derivation and release testing; differentiation fidelity, maturation, and potency; genomic stability and tumorigenicity risk; graft survival, synaptic integration, and immune rejection despite ocular immune privilege; the scarcity of validated biomarkers and harmonized outcome measures and ethical, regulatory, and health-economic constraints. Promising trajectories span off-the-shelf allogeneic products, patient-specific iPSC-derived grafts, organoid and 3D-bioprinted tissues, gene-plus-cell combinations, and cell-free extracellular-vesicle therapeutics. Overall, cell-based therapies remain investigational. With adequately powered trials, methodological harmonization, long-term surveillance, scalable xeno-free manufacturing, and equitable access frameworks, they may eventually become standards of care; at present, approvals are limited to specific products/indications and regions, and no cell therapy is the standard of care for retinal disease. Full article

Autoimmune liver diseases (AILDs) represent a diverse spectrum of chronic inflammatory conditions characterized primarily by compromised hepatic immune tolerance, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Recent evidence positions macrophages as pivotal players in AILDs pathogenesis, attributable to their multifaceted roles in inflammation amplification, immune regulation, and fibrogenesis. In the context of AILDs, macrophages exhibit marked polarization imbalance, increased recruitment of monocytes, and impaired clearance of apoptotic cells. Through complex interactions with T lymphocytes and hepatic stellate cells, macrophages orchestrate a pathological milieu promoting inflammation and fibrosis. Notably, diverse programmed cell death (PCD) modalities—autophagy, necroptosis, pyroptosis, and ferroptosis—not only determine macrophage survival and functional phenotype but also significantly impact cytokine release, phenotypic plasticity, and the trajectory of immunopathological progression. This review synthesizes current understandings of macrophage-driven immunoregulatory mechanisms in AILDs, characterizes the regulatory attributes of various macrophage-related PCD processes, and evaluates their relevance in experimental disease models. Furthermore, we highlight recent advancements in biomarker identification and targeted therapeutic strategies. Comprehensive elucidation of the interplay between macrophage immunological activity and programmed cell death pathways promises to inform novel, personalized therapeutic approaches for patients with AILDs. Full article

Polypharmacology in Amyotrophic lateral sclerosis (ALS) demands models that capture irreducible higher-order drug co-action. We introduce a categorical–topological pipeline that encodes regimens as truncated multicomplexes with a hypergraph–simplicial envelope; irreducible effects are identified by Möbius inversion, and CatMixNet predicts dose-response under monotone calibration while aligning multimodal omics via sheaf constraints. Under face-disjoint evaluation, omics fusion reduced RMSE from 0.164 to 0.149 (≈9%), increased PR-AUC from 0.38 to 0.44, and lowered calibration error to 2.6–3.1% with <10 dose-monotonicity violations per ${10}^3$ surfaces. Triad-irreducible signal strengthened (95th percentile ${\mathsf{\Delta }}^{★}=0.151$; antagonism retained at 24%). A risk-sensitive selector produced triads with toxicity headroom and projected ALSFRS-R slope gains of +0.04–0.05 points/month. Ablations confirmed the necessity of Möbius consistency, sheaf regularization, and monotone heads. Distilled monotone splines yielded compact titration charts with mean error 0.023. The framework supplies reproducible artifacts and actionable shortlists for iPSC and SOD1 validation. Full article

This study quantifies shear and flexural stiffnesses and their changes over time to support structural health monitoring of in-service bridge superstructures across four girder types: reinforced concrete (RC) beams, prestressed concrete (PSC) girders, steel girders, and ultra-high-performance concrete (UHPC) sections, using field ambient vibration testing. A total of 20 bridges across Georgia and Iowa are assessed, involving over 100 hours of on-site data collection and traffic control strategies. Results show that field-measured natural frequencies differ from theoretical predictions by average of 30–35% for RC, and 20–25% for PSC, 15–25% for steel and 2% for UHPC, reflecting the complexity of in situ structural dynamics and challenges in estimating material properties. Site-placed RC beams showed stiffness reduction due to deterioration, whereas prefabricated PSC girders maintained consistent stiffness with predictable variations. UHPC sections exhibited the highest stiffness, reflecting superior performance. Steel girders matched theoretical values, but a span-level test revealed that deck damage can reduce frequencies undetected by localized measurements. Importantly, vibration-based measurements revealed reductions in structural stiffness that were not apparent through conventional visual inspection, particularly in RC beams. The research significance of this work lies in establishing a portfolio-based framework that enables cross-comparison of stiffness behavior across multiple girder types, providing a scalable and field-validated approach for system-level bridge health monitoring and serving as a quantitative metric to support bridge inspections and decision-making. Full article

The purpose of this parametric study was to develop a numerical simulation model calibrated with experimental data to predict the flexural behavior of prestressed concrete (PSC) girders subjected to long-term prestress losses. The model is capable of accurately simulating the flexural behavior of PSC girders using commercial finite-element (FE) software in the ABAQUS/Explicit program. The accuracy of the model was validated by comparing its results with flexural response test data from three post-tensioned girders, with the tendons ultimately having tensile strength capacities of 1860 MPa, 2160 MPa, and 2400 MPa. The comparison demonstrated generally excellent agreement between numerical and experimental results in terms of the load–deflection response and crack propagation behavior, from the onset of first cracking through the maximum load and into the ductile response range. Subsequently, a parametric study was conducted to evaluate the effects of tendon ultimate strength, amount of long-term prestress loss, grouting defects, degradation-induced reductions in concrete strength, and reductions in tendon cross-sectional area on girder flexural behavior. Through this parametric investigation, the study identified key factors with respect to long-term prestress loss that may influence the flexural behavior of aging PSC structures. Full article

Schizophrenia is a highly polygenic and clinically heterogeneous disorder. In this paper, we first review layer-specific evidence across genetics, epigenetics, transcriptomics, proteomics, and patient-derived induced pluripotent stem cell (iPSC) models, then integrate cross-layer findings. Genetics research identifies widespread risk architecture. Hundreds of loci from common, rare, and CNV analyses. Epigenetics reveals disease-associated DNA methylation and histone-mark changes. These occur at neuronally active enhancers and promoters, together with chromatin contacts that link non-coding risk to target genes. Transcriptomics show broad differential expression, isoform-level dysregulation, and disrupted co-expression modules. These alterations span synaptic signaling, mitochondrial bioenergetics, and immune programs. Proteomics demonstrates coordinated decreases in postsynaptic scaffold and mitochondrial respiratory-chain proteins in cortex, with complementary inflammatory signatures in serum/plasma. iPSC models recapitulate disease-relevant phenotypes: including fewer synaptic puncta and excitatory postsynaptic currents, electrophysiological immaturity, oxidative stress, and progenitor vulnerability. These same models show partial rescue under targeted perturbations. Integration across layers highlights convergent pathways repeatedly supported by ≥3 independent data types: synaptic signaling, immune/complement regulation, mitochondrial/energetic function, neurodevelopmental programs and cell-adhesion complexes. Within these axes, several cross-layer convergence genes/proteins (e.g., DLG4/PSD-95, C4A, RELN, NRXN1/NLGN1, OXPHOS subunits, POU3F2/BRN2, PTN) recur across cohorts and modalities. Framing results through cross-layer and shared-pathway convergence organizes heterogeneous evidence and prioritizes targets for mechanistic dissection, biomarker development, and translational follow-up. Full article