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Preoptic kisspeptin-nNOS-GnRH (KiNG) neuronal network regulates LH rhythmicity through activation-inhibition in mice

Pruning tree forest and re-sampling for class imbalanced problem

<i>Microraptor</i> reveals specialized gliding capabilities in multiwinged early paravians

Agile and efficient modern flyers like birds and insects rely on complex aerodynamics to increase performance such as leading edge vortices, tip vortices, rapid pitch rotations as well as wing–wake and wing–wing interactions. However, their evolutionary origins are poorly understood. Early birds and their closest relatives like Microraptor had a multiwinged configuration featuring long pennaceous feathers on their arms, legs, and tail, a configuration not seen today. The skill of these early flyers has been debated, centering around what was driving the evolution of this multiwing configuration and its loss in favor of the modern two-winged configuration. In this context, the aerodynamics and wing–wing interactions of Microraptor during gliding flight are investigated. The gliding flight mechanics of Microraptor exhibit flow patterns consistent with those observed and quantitatively assessed in volant living animal species. We analyze leading edge vortices on the forewing and hindwing including beneficial wake interactions between them as well as tip vortices on the distinct distally flared hindwing. The latter is unique in Microraptor as the hindwing’s characteristic outer span flare provides the necessary surface for the tip vortex to be bound to and thus contribute additional lift. These findings suggest that Microraptor evolved toward utilizing leading edge and tip vortices and their aerodynamic interactions. This implies that such utilization was also being exploited by other early multiwinged theropods to differing extents as part of a crucial milestone in early flight evolution.

Pulmonary fibroblasts activated by the addition of TNF-α and IL-4 enhance lymphangiogenic capacity and ameliorate lung fibrosis in an allogeneic rat model

Background Pulmonary fibrosis remains a major clinical challenge with limited treatment options. Recent studies have suggested that fibroblasts, when stimulated by specific cytokines, may acquire lymphangiogenic and antifibrotic properties contributing to tissue repair. Methods Human and rat pulmonary fibroblasts (PFs) were stimulated with TNF-α and IL-4 to induce lymphangiogenic and antifibrotic characteristics. In vitro analyses assessed gene expression, cytokine secretion, tube formation capacity, and immunogenicity. Therapeutic efficacy was evaluated in a rat model of bleomycin-induced pulmonary fibrosis following allogeneic PF transplantation. Results Cytokine-stimulated PFs exhibited upregulation of ADM and VEGFC , enhanced tube formation capacity, and minimal expression of immunogenic markers. In vivo, allogeneic PF transplantation significantly reduced fibrotic lesion and plasma SP-D levels compared to controls. Gene expression analyses demonstrated downregulation of fibrosis-associated markers after treatment. Conclusion Cytokine-stimulated pulmonary fibroblasts may serve as a novel cell source for antifibrotic therapy by modulating lymphangiogenesis and tissue remodeling, providing a potential alternative to conventional stem cell-based approaches for fibrotic lung diseases.

Ultrafast scintillating metal-organic framework films

Balancing environmental benefits and accessibility for national park buffer zones in China

Morphological characterization of Calotropis procera (Aiton) W.T. Aiton, a neglected medicinal plant

Calotropis procera (Aiton) W.T. Aiton, a medicinally significant but understudied species, exhibits remarkable adaptability to arid environments. Despite its ecological and pharmacological value, the species remains poorly characterized morphologically. This study evaluated the morphological diversity of 50 C. procera accessions from Sistan-va-Baluchestan province, Iran, using multivariate statistical approaches to identify key phenotypic variations and their potential applications. Significant morphological variability was observed among the accessions, with 37 out of 53 traits exhibiting coefficients of variation greater than 20%. Fruit-related traits, such as fruit length and weight, exhibited the highest variability, with the first principal component (PC1) explaining 17.45% of the total variance. Leaf characteristics, including color and pubescence, were dominant in the second principal component (PC2), accounting for 14.53% of the variance. Multiple regression analysis revealed a strong positive correlation between fruit weight and fruit length ( β  = 0.73, p  ≤ 0.00). A trade-off was observed between flower number and fruit weight ( β  = −0.32, p  ≤ 0.00). Heat map analysis grouped the accessions into four distinct clusters, with ‘Roodan-10’ and ‘Bahoukalat-1’ standing out for their superior fruit and floral traits, respectively. Notably, accessions such as ‘Dargas-10’ (100-seed weight: 2.40 g), ‘Rask-8’ (seed hair length: 30.19 mm), and ‘Pishin-8,’ distinguished by its exceptional leaf dimensions (mature leaf width: 139.20 mm), were identified as potential candidates for breeding. The remarkable leaf size of ‘Pishin-8’ suggests a high level of photosynthetic efficiency, which could enhance biomass production, further contributing to the ecological and agronomic value of this accession due to its exceptional seed characteristics. This study provides the first comprehensive morphological evaluation of C. procera , highlighting its high phenotypic diversity and adaptive traits. The findings underscore the species’ potential for medicinal and ecological applications, with specific accessions offering valuable genetic resources for conservation and breeding programs. Future research integrating molecular analyses is recommended to elucidate the genetic basis of observed variations.

Daily briefing: Caffeine might reduce dementia risk and slow cognitive decline

Over a century of global decline in the growth performance of marine fishes

Abstract Human-driven pressures are causing large-scale changes in the ecologies and life histories of fishes. Growth performance is a composite life-history trait that captures the trade-off between two fundamental traits: growth and body size. Here, we assess the impacts of fishing and temperature on the growth performance of marine teleost fishes globally over the last century. Using 7683 growth curves encompassing 1479 species, we find a global pattern of decline in growth performance from 1908 onwards, with the greatest declines in commercially valuable fishes. Indeed, managed fisheries experienced a 9% decline in growth performance over the last century, which can equate to an average decline of up to 23% in asymptotic body size or a 45% decline in the von Bertalanffy growth coefficient ( K ). Despite relatively consistent increases in ocean temperatures globally, we only detect a decline in the growth performance of fishes in temperate regions, which is probably indicative of an overrepresentation of commercially valuable fishes at higher latitudes. The declines in growth performance likely reflect legacy effects, shaped by overfishing, on changes in the underlying size structure and demographic processes of fished stocks. Therefore, the potential impacts of warmer temperatures on growth performance may be overwhelmingly masked by the impacts of overfishing.

FAM120A - a protein inserted in the ALS disease network

Computational elucidation of stomidazolone mediated inhibition of stomatal differentiation and its implication in plant developmental regulation

Stomata play a critical role in plant physiology by balancing gas exchange and water conservation. Their development is driven by a precisely orchestrated sequence of cell divisions and differentiation events, regulated by basic helix-loop-helix (bHLH) transcription factors such as MUTE. Previous research reports stomidazolone, a doubly sulfonylated imidazolone derivative, as an effective inhibitor of stomatal development which has been shown to bind strongly to MUTE, interfering with its interaction with SCRM, effectively suppressing stomatal differentiation. The ACTL domain, a conserved structural feature in plant bHLH proteins, acts as a potential site for chemical inhibition, enabling selective disruption of stomatal formation. This suggests a promising approach for enhancing drought resilience in plants by reducing water loss through transpiration. While experimental data support stomidazolone’s inhibitory role, the molecular details of its binding to MUTE remain inadequately characterized. To address this gap, a comprehensive in silico analysis combining molecular docking and density functional theory (DFT) was performed to elucidate the binding interactions, electronic properties, and reactive potential of stomidazolone, thereby uncovering the molecular features that underpin its affinity and specificity toward MUTE. An all-atom molecular dynamics (MD) simulations was then carried out to provide mechanistic insights beyond static binding models, followed by a number of post-simulation analyses assessing system stability and dynamics to gain deeper insight into the Stomidazolone-Mediated Inhibition of MUTE. Our results reveal the formation of a stable and compact stomidazolone–MUTE complex, characterized by a lower average RMSD (1.45 ± 0.12 nm) compared to the Apo state (1.65 ± 0.18 nm), while hydrogen bonding analysis further demonstrated persistent interactions involving Arg62 and Ser69, along with a stabilizing contribution from Glu163, collectively supporting the strong binding affinity of stomidazolone within the MUTE active site. Principal component analysis further highlighted the conformational coherence and coordinated atomic motion, while the free energy landscape showed well-defined energy minima, underscoring the stability of the interaction and energetic favorability of the complex. Together, these findings provide a molecular framework for understanding the inhibitory mechanism of stomidazolone on MUTE, offering a basis for the rational design of next-generation agrochemicals targeting stomatal development. The study also highlights the conceptual novelty of small-molecule modulation of lineage-specific transcription factors as a potential strategy for the synthetic control of plant developmental plasticity. While the results are computational, they outline clear directions for experimental validation and scaffold optimization, paving the way for future efforts to translate these insights into practical applications for improving crop resilience and water-use efficiency. Importantly, this study provides the first mechanistic, residue-level insight into how stomidazolone engages the ACT-Like (ACTL) domain of MUTE, revealing the specific molecular interactions and dynamic features that underpin its inhibitory effect.

Ultrafast visual perception beyond human capabilities enabled by motion analysis using synaptic transistors

Multi-omics identification of key targets for the osteogenic differentiation of human bone marrow mesenchymal stromal cells under oxidative stress

Abstract Human bone marrow mesenchymal stromal cells (hBMSCs) are multipotent stromal cells capable of osteogenic differentiation, making them a promising cell source for bone tissue engineering and regenerative medicine. Identifying key factors that regulate hBMSCs osteogenic differentiation is crucial for enhancing bone regeneration strategies. This study aims to identify target genes underlying impaired osteogenic differentiation of hBMSCs under oxidative stress (OS) through integrated transcriptomic and proteomic approaches, and delineate the role of proenkephalin (PENK) in this process. OS model and impaired osteogenic differentiation model were established in hBMSCs using hydrogen peroxide (H 2 O 2 ). Cellular oxidative stress levels were assessed using Dihydroethidium (DHE) fluorescent probes and JC-1 staining. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity and Alizarin Red staining (ARS). Key genes and proteins were predicted via integrated transcriptomic and proteomic analyses. The role of PENK in osteogenic differentiation was validated using lentiviral transfection. This study established 400 µM H 2 O 2 as the optimal concentration for inducing impaired osteogenic differentiation in hBMSCs. Integrated transcriptomic and proteomic analysis identified 18 pivotal regulatory genes that orchestrate impaired osteogenic differentiation of hBMSCs under OS. Among these, PENK was identified as a potential therapeutic target involved in regulating oxidative stress-impaired osteogenic differentiation of hBMSCs. Functional validation confirmed that PENK overexpression promotes osteogenic differentiation in hBMSCs. OS contributes to impaired osteogenic differentiation in hBMSCs. PENK regulates osteogenic differentiation of hBMSCs under OS and holds promise as a novel therapeutic target for bone regeneration and repair.

Investigations of a new EPS-insulated mortar-free reusable interlocking block for sustainable buildings

Sustainable, energy-efficient, and reusable construction systems have increasingly been demanded due to the increasing amount of plastics, waste, demolition debris, and the carbon footprints associated with existing traditional materials used in the construction industry. In contribution to this, this study innovates a new enveloped insulated interlocking concrete block (IICB) made of recycled aggregate concrete (RAC) and expanded polystyrene (EPS), which can be shortened to EIICB. This innovation aims to maximize the potential of producing thermally insulated blocks at full scale, focusing on features such as portability, dry assembly, speedy execution, reusability, inventiveness, high compression, low absorption, and sustainability, which cannot be fully achieved by previous concrete blocks. Compared with conventional concrete blocks, the EIICB reduces concrete material usage and achieves an estimated 73.5% reduction in CO₂ emissions. Experimental evaluation showed an average compressive strength of 7.91 MPa, water absorption of 4.74%, and a calculated thermal R-value of 15.05, demonstrating improved thermal efficiency and compliance with structural requirements for non-load-bearing and light structural applications. This work has provided key benefits: transforming waste concrete into valuable materials for affordable and sustainable construction, providing energy-efficient solutions for modern construction, protecting the environment, and aligning with sustainable building practices. The results from this study show the EIICB’s ability to promote the construction of low-cost, energy-efficient housing and indicate future opportunities for optimization, full-scale thermal validation, and life-cycle performance assessment.

Author Correction: Whole-body CD8+ T-cell PET imaging in patients with large B-cell lymphoma before and during CD19-directed CAR T-cell therapy: a phase 2 study

BMSCs exosomes regulate pulmonary microvascular endothelial apoptosis via circRNA_43350/miR-342-5p in COPD

Correction: Co-generation of NaREE(MoO4)2 and REEPO4 in multiple habits by solid-flux crystal growth

Degraders of the dengue virus capsid protein exhibit differentiated pharmacology relative to capsid inhibitors

Abstract Due to the limited size of viral genomes, most viral proteins are multifunctional; yet most direct-acting antivirals are designed as single-function inhibitors. The dengue virus (DENV) capsid protein serves as a building block for new virions while also interacting with multiple host factors to remodel the cellular environment. Using established capsid inhibitor ST148 as a targeting ligand, we develop a DENV capsid degrader, RPG-01-132, that exhibits a broadened spectrum of activity against the four DENV serotypes and an ST148-resistant mutant virus. Using multiple approaches, we show that RPG-01-132’s sub-micromolar antiviral activity is due to CRL4 CRBN -dependent degradation of capsid and that this mechanism disrupts capsid-related pathways required for productive infection, including infectious virus output and capsid-mediated antagonism of the interferon response. This pharmacology is well-differentiated from ST148, which interferes with assembly of new virions, but has no demonstrated effect on the capsid’s nonstructural functions. These findings demonstrate that targeted protein degradation can thus enable antiviral pharmacology not observed with conventional antiviral inhibitors and that is resilient to point mutations that reduce inhibitor potency.

Optimized scheduling of integrated energy systems considering waste-to-power plants and advanced adiabatic air compression energy storage machines

Abstract To achieve carbon peaking and carbon neutrality goals, improve energy utilization efficiency, and accelerate the decarbonization of energy structure, this paper proposes a model that integrates Waste Incineration Power Plant (WIP) and Advanced Adiabatic Compressed Air Energy Storage (AA-CAES) to reduce carbon emissions and enhance system economics. First, based on the coupled WIP and Power-to-Gas (P2G) model, a waste heat recovery unit is introduced to recover exhaust heat and reduce purchase heat cost. Second, Power-to-Ammonia (P2A) technology is integrated with coal-fired generating units to enable dynamic ammonia-coal co-firing, further reducing carbon emissions and enhancing renewable energy utilization. Third, AA-CAES is incorporated to expand heat supply channels through compression heat storage and release, while absorbing heat during expansion power generation, thus achieving cross-temporal heat utilization and establishing a coordinated power and heat supply model between energy storage equipment and WIP. Finally, an improved Particle Swarm Optimization algorithm with dynamically adjusted inertia weights and learning factors, combined with a local exchange strategy, is employed for optimization. Case study results demonstrate that the proposed improved algorithm achieves lower total cost, and the coordinated operation of AA-CAES with WIP reduces the total system cost by 20.03%.

Smallpox outbreak scenarios and reactive intervention protocols: A mathematical model-based analysis applied to the Republic of Korea

Smallpox, caused by the variola virus, remains a potential biosecurity threat despite its eradication. This study develops a mathematical model to evaluate outbreak scenarios and the effectiveness of reactive intervention strategies in controlling transmission, with application to the Republic of Korea. The model incorporates age-stratified contact patterns, contact tracing, and vaccination strategies, including targeted vaccination and mass vaccination. Our simulations demonstrate that early outbreak recognition and rapid intervention are critical in mitigating smallpox spread. In scenarios where vaccination rollout was slow or outbreak recognition was delayed, severe patient numbers exceeded healthcare capacity, highlighting the need for preemptive preparedness. Sensitivity analyses revealed that outbreak recognition timing and contact tracing effectiveness were the most influential factors in determining outbreak severity, with later recognition leading to up to 3.5 times more cumulative cases. Furthermore, we compared different vaccination prioritization strategies and found that prioritizing high-transmission age groups was more effective in reducing total mortality than prioritizing high-risk groups based solely on disease severity. This contrasts with COVID-19 vaccination strategies, which focused on protecting vulnerable populations. These findings underscore the importance of early detection, strategic vaccination, and non-pharmaceutical interventions in mitigating a potential smallpox outbreak. Our model provides a quantitative framework for policymakers to evaluate intervention effectiveness and optimize outbreak response strategies.