Browse Articles

Adipose Dicer-1 modulates systemic insulin signaling and longevity via a miR-8–Aop–Dilp6 axis

Interorgan communication is essential for metabolic homeostasis and healthy aging, with adipose tissue acting as a central hub that coordinates systemic metabolism, stress responses, and longevity. Here, we show that the miRNA-processing enzyme Dicer-1 (Dcr-1) acts in the fat body (FB) to regulate Dilp2 secretion from brain insulin-producing cells (IPCs), thereby modulating systemic insulin signaling and lifespan in Drosophila . Dcr-1 expression is reduced in multiple long-lived conditions, and its partial downregulation enhances oxidative stress resistance, alters lipid metabolism, and extends lifespan even under dietary restriction. Proteomic profiling of FBs from Dcr-1 heterozygous flies revealed widespread metabolic reprogramming and stress adaptation consistent with attenuated insulin/IGF signaling (IIS). Mechanistically, reduced Dcr-1 lowers miR-8 levels in the FB, which indirectly upregulates Drosophila insulin-like peptide 6 (Dilp6). Dilp6 acts nonautonomously to suppress Dilp2 secretion from IPCs, reducing systemic IIS and promoting longevity. We further show that Dcr-1 reduction activates the ETS-family repressor Aop/ETV6 downstream of Ras-Erk signaling, which is required for Dilp6 induction and the lifespan extension observed upon miR-8 depletion. Collectively, these findings reveal a miRNA-dependent regulatory axis that couples adipose-derived endocrine signals to systemic insulin regulation and aging, positioning Dcr-1 as a central node in the control of metabolic homeostasis and lifespan.

Enhancing industrial acoustic environments through a mathematical model and 3D COMSOL acoustic simulation

Abstract Legislators and manufacturing clients often drive engineering firms to adopt noise reduction measures early in community projects. This paper introduces a mathematical model and simulation tools to analyze sound propagation impacts at acceptable distances by optimizing machine placement based on sound engineering principles. A 3D acoustic simulation program, employing a diffusion equation model, forecasts noise distribution levels before and after machine layout modifications using a genetic algorithm. Our study took place in a spinning factory, where the optimized machine layout improved indoor acoustic conditions from 91.22 dB to 88.17 dB. This framework effectively reduces the daily work exposure level (LEX, 8 h) in the textile industry by 3.344%.

Small molecule–constrained paratope mimetic bicyclic peptides as potent inhibitors of group 1 and 2 influenza A virus hemagglutinins

Influenza continues to be a major threat to global health and a substantial economic burden. Innovative strategies are needed to tackle the growing resistance to established influenza therapeutics and to develop new therapeutics with novel mechanisms of action. Previous peptide and small molecule designs have been successful only against influenza group 1 hemagglutinin (HA). Here, we report on a CLIPS (Chemical Linkage of Peptides onto Scaffolds)-based approach to design potent peptidic inhibitors of influenza A viruses that now extend to both group 1 and group 2 HAs. This approach merges features of antibodies and small molecules to design constrained bicyclic peptides that engage the highly conserved HA stem. The heavy-chain complementarity-determining region 3 (HCDR3) of human broadly neutralizing antibody FI6v3 was grafted onto functionalized small molecule scaffolds. The designed peptides exhibited in vitro heterosubtypic cross-reactivity in binding to group 1 (H1 and H5) and group 2 (H3 and H7) HAs and in neutralization of H1N1, H5N1, and H7N3 viruses. A crystal structure of the bicyclic peptide with HA from H1N1 A/Puerto Rico/8/1934 (H1/PR8) at 2.35 Å resolution revealed that the designed peptide faithfully mimics the binding mode and functionality of the parent antibody FI6v3 to the highly conserved stem epitope. These structural and functional data illustrate how both group 1 and group 2 influenza A viruses can now be targeted by constrained peptidic ligands that should aid in development of pan-influenza therapeutics.

Rotary cutting tests and rock-breaking characteristics of triple-ridged PDC cutters in tight hard sandstones from Xujiahe Formation in Sichuan Basin in China

The phospholipid profile of T cells shapes ACSL4 dependency and ferroptosis sensitivity of naive, effector, and memory T cells

Iron-dependent phospholipid (PL) peroxidation, which is reduced by glutathione peroxidase 4, is recognized as the hallmark of cells undergoing ferroptosis. Although studies have attempted to elucidate the molecular mechanisms underlying ferroptosis in cancer cells, the regulation of ferroptosis in effector and memory T cells remains largely unknown. Here, using genome-wide CRISPR-Cas9 knockout screens, we demonstrate that acyl-CoA synthetase long-chain family member 4 (ACSL4) is the predominant ferroptosis inducer in primary T cells cultured in vitro, while other identified iron- and lipid metabolism–related genes only slightly modulate their sensitivity to ferroptosis. However, ACSL4 dependency relies on the PL composition of the cells. In vitro cultured T cells treated with polyunsaturated fatty acids (PUFAs), as well as effector CD8 + T cells that are enriched in PUFA-containing PLs (PUFA-PLs), undergo ferroptosis in the absence of ACSL4. In contrast to effector T cells, naive and memory T cells share a similar PL profile, characterized by a scarcity of PUFA-PLs, and are resistant to ferroptosis. Overall, the PL composition is a central feature and determines the differential susceptibility of effector and memory T cells to ferroptosis and its molecular mechanism.

Differential effects of cognitive training and aerobic exercise on regional gray matter volume and inter-regional covariance in community-dwelling older adults

Self-regulated dual-mode solar energy harvesting

Traditional solar energy harvesters are single-mode—typically designed to convert available sunlight either into heat or electricity. However, neither energy form is continuously useful, and an optimal variant should instead be capable of autonomously toggling relative thermal and electrical yield based on need. Here, we introduce passive, dual-mode indoor solar energy harvesting by using a fluid layer trapped above a Fresnel lens as a phase-changing switch within a solar waveguide. When warm out and electricity is desired, the fluid is in its vapor phase, causing a refractive index difference with the microstructured lens beneath it to concentrate sunlight toward a solar cell. When cold out and heat is instead desired, the fluid condenses atop the Fresnel structure to reduce refractive index differences, causing sunlight to refract past the solar cell and convert to heat when absorbed indoors. Using water as a phase-changing switch, we built an exemplary system that self-regulates indoor temperature and solar cell light exposure over ambient heating and cooling cycles. Our approach is general across everyday materials and manufacturing methods and may be deployed on the surfaces of vehicles, greenhouses, and residential or commercial buildings.

Novel green UPLC method with life cycle assessment for determination of favipiravir and molnupiravir drugs and environmental water samples

Abstract A novel green UPLC–SPE analytical method was developed for the simultaneous determination of Favipiravir (FVP) and Molnupiravir (MPV) in pharmaceutical and environmental water samples. The method was designed to address the analytical gap surrounding concurrent antiviral monitoring given their co-administration while minimizing solvent consumption, waste generation, and environmental impact. Water samples preparation employed a solid-phase extraction strategy optimized through systematic evaluation of sorbent type, conditioning, washing, and elution steps. Chromatographic separation was achieved using a mobile phase consisting of 0.01 M potassium dihydrogen phosphate buffer (pH 3.5) and 50% methanol (85:15, v/v), delivered at a flow rate of 0.2 mL/min with a 10 µL injection volume. This method produced sharp, well-resolved peaks with a total run time of less than 5 min. The method exhibited excellent linearity (r² ≥ 0.999), accuracy (98.56–101.19%), precision (RSD ≤ 1.8%), and recoveries of (98.97- 100.74%) across tap water, Nile River water, and pharmaceutical wastewater. Greenness was assessed using the Multi-Color Assessment (MA) platform, yielding a final whiteness score of 85.7%, which indicates a well-balanced integration of environmental, practical, analytical, and innovative attributes and supports the method’s suitability for routine application. The Analytical Eco-Scale score (77) and AGREE pictogram score (0.84) further confirm the strong environmental compatibility of the proposed method. Life cycle assessment (LCA) revealed substantial reductions in energy consumption and waste generation compared with conventional HPLC methods. Overall, the proposed UPLC–SPE approach, integrated with LCA and comprehensive greenness evaluation, represents a pioneering and environmentally informed strategy for antiviral analysis and provides a sustainable platform for future pharmaceutical residue monitoring.

Correction for Goyette et al., Targeting Axl favors an antitumorigenic microenvironment that enhances immunotherapy responses by decreasing Hif-1α levels

Extensive screening of ten bacteriophage cocktails revealed an optimal combination with potent therapeutic activity against Acinetobacter baumannii

Mechanism of 30S subunit recognition and modification by the conserved bacterial ribosomal RNA methyltransferase RsmI

Ribosomal RNA (rRNA) modifications are important for ribosome function and can influence bacterial susceptibility to ribosome-targeting antibiotics. The universally conserved 16S rRNA nucleotide C1402, for example, is the only 2’- O -methylated nucleotide in the bacterial small (30S) ribosomal subunit and this modification fine-tunes the shape and structure of the peptidyl tRNA binding site. The Cm1402 modification is incorporated by the conserved bacterial 16S rRNA methyltransferase RsmI, but it is unclear how RsmI recognizes its 30S substrate and specifically modify its buried target nucleotide. We determined a 2.42 Å resolution cryo-EM structure of the RsmI–30S complex and, with accompanying functional analyses, show that RsmI anchors itself to the 30S subunit through multiple contacts with a conserved 16S rRNA surface previously only seen in the assembled subunit. This positions RsmI to bind a h44 conformation that is substantially reorganized compared to its structure in the mature 30S subunit allowing access to C1402. These analyses also reveal an essential contribution to 30S subunit interaction made by the previously structurally uncharacterized RsmI C-terminal domain, RsmI-induced RNA–RNA interactions with C1402, and an unappreciated dependence on a divalent metal ion for activity that suggests RsmI may be a member of a distinct class of metal- and SAM-dependent RNA O -methyltransferases. This study significantly expands our mechanistic understanding of how intrinsic bacterial methyltransferases like RsmI modify their rRNA targets. Further, recognition of distant ribosome features and reorganization of a critical rRNA functional center point to a potential role in accurate 30S subunit biogenesis.

Deception in orbital games: simulation and dissimulation with a maneuverable decoy

GFAP ⁺ FOXF2 ⁺ ependymal cells promote blood–brain barrier repair via DLL4–NOTCH signaling after neural injury

Ependymal cells in the adult ventricular-subventricular zone are increasingly recognized for functions extending beyond cerebrospinal fluid dynamics; however, their identity and functional specialization remain incompletely understood. While ependymal cells (EP) have been implicated in interactions with the stem cell niche and the vasculature, their role in repair processes following neural injury remains elusive. In this study, we employed region-specific single-cell transcriptomics of the subventricular zone (SVZ) and ipsilesional peri-infarct territory in mice to identify a distinct subpopulation of GFAP + FOXF2 + EP that selectively expand within the SVZ after neural injury. Notably, these cells were absent from other brain regions. Immunohistochemical validation revealed characteristic ependymal features, including typical pinwheel architecture and expression of Foxj1 and β-catenin. Furthermore, the absence of the proliferation marker Ki67 and the resistance of this subpopulation to Ara-C-mediated ablation indicate that these cells do not possess proliferative properties. Conditional deletion of Foxf2 in GFAP + cells led to impaired endothelial junction integrity and increased blood–brain barrier (BBB) permeability. In contrast, overexpression of Foxf2 via GFAP promoter-driven adeno-associated virus delivery enhanced vascular repair and facilitated functional recovery. Mechanistically, these GFAP + FOXF2 + EP secrete exosomal DLL4, which was associated with enhanced NOTCH pathway activity and restoration of BBB function. While the mechanism linking this limited cell population to the broad reparative effect, particularly the complete signaling amplification cascade, remains to be fully elucidated, these findings identify a subset of EP that contributes to BBB repair.

High-resolution assessment of wind energy resources over the Arabian Peninsula

Depth of nutrient uptake by deep-rooted plants is regulated by water availability

The capacity of some plants to access water and nutrients at depths greater than one meter is a critical functional trait that confers resistance to drought and impacts both belowground and shallow soil processes. Here, we report water and strontium isotopic data from an alpine meadow transect showing the correlation between water and nutrient acquisition depths. The isotopic compositions of Sr ( 87 Sr/ 86 Sr ratio) and water in rock and soil, and in plant leaf tissues, reveal that deeper-rooted plants acquire a higher proportion of water, Sr, and cation nutrients that are derived from the saprolite, a zone of silicate weathering, than shallow-rooted grass. A three-decade dendrochemical record reveals that reductions of wet precipitation drive deep-rooted plants to acquire cation nutrients from deeper saprolite or bedrock regions. Thus, the depth of cation nutrient acquisition by deep-rooted plant species at this site is tightly coupled with, and likely determined by, water availability in soil, saprolite, and bedrock. The enhanced uptake of cations as well as water from deeper saprolite zones could impact the rate of bedrock weathering and watershed chemistry during drought.

Morphology-guided deep learning for nanoparticle agglomeration diagnostic assays

Fab–Fc and Fab–Fab interactions of variable strength and valency contribute to the high concentration viscosity of IgG ₁ antibodies

The variable domains in Fab regions are well-established contributors to high concentration viscosity of IgG, primarily through charge and hydrophobic interactions. In contrast, the roles of the Fc and the number of self-interacting sites (valency) are less well understood. Here, we investigate the relative contributions of Fab–Fab and Fab–Fc interactions to high concentration viscosity for a diverse panel of 20 IgG 1 antibodies, by rheometry, coarse-grained simulations, and molecular surface property analysis. Strikingly, fragmentation of IgG 1 into F(ab′) 2 plus Fc reduced viscosity (−11 to −93%) for all antibodies tested, demonstrating prevalent contributions of Fc to viscosity. Coarse-grained simulations with one site per Fab and two sites per Fc qualitatively tracked trends in experimental rheometry data for 20 parental antibodies and their fragments. In these simulations Fab–Fab and Fab–Fc interaction strengths were independently varied to capture possible interaction differences arising from parental sequences or any mutations. These coarse-grained simulations suggest that Fab–Fc attractions generate branched IgG 1 networks and disproportionately larger clusters relative to Fab–Fab interactions of comparable strength. This study suggests that a four-site self-interaction model, previously proposed for a single antibody (omalizumab), is broadly applicable to diverse IgG 1 . Beyond well-established variable domain engineering, this self-interaction model predicts that Fc engineering may reduce IgG 1 viscosity, a much sought after goal to enable subcutaneous delivery. Clinically validated Fc mutations are demonstrated here to substantially reduce the viscosity for multiple IgG 1 (−33 to −91% reduction, n = 6), supporting this emerging antibody design concept.

Phase behavior and reservoir fluid classification of the deep Permian Jiamuhe formation gas condensate in Zhongjia area, Junggar Basin

The m5C orchestrator NSUN7 drives SPARC/HMGB1 axis–mediated inflammation to exacerbate kidney injury

Growing evidence indicates that kidney inflammation is a major contributor to the pathogenesis of various renal diseases, including acute kidney injury (AKI). Although RNA modifications have been implicated in regulating kidney inflammation, their precise roles remain largely unknown. Here, we show that kidney inflammation and injury were associated with elevated RNA 5-methylcytosine (m5C) modifications, primarily driven by the NOP2/Sun RNA methyltransferase family member 7 (NSUN7). Both global and kidney-specific deletion of Nsun7 in mice reduced m5C abundance, attenuated inflammatory responses, and decreased macrophage infiltration, underscoring its proinflammatory role in the kidney. Mechanistically, we identified secreted protein acidic and cysteine-rich (SPARC) as a major downstream effector of NSUN7. SPARC upregulation amplified inflammatory responses in renal tubular epithelial cells by interacting with high mobility group box 1 and further promoted proinflammatory macrophage infiltration via tubular-macrophage crosstalk. Notably, therapeutic silencing of Nsun7 using a kidney-specific DNA tetrahedral molecular carrier developed for this study effectively alleviated inflammation and improved renal outcomes in AKI models. Collectively, our findings identify NSUN7 as a key driver of renal inflammation via SPARC regulation and underscore its potential as a therapeutic target in inflammatory kidney diseases.

Strengthening RC beams and columns with CFRP, GFRP and KFRP laminates

Abstract Prolonged exposure to adverse conditions affects the performance and promotes the degradation of reinforced concrete (RC) structures, requiring repair and strengthening to preserve their integrity and functionality. Synthetic fibers, including carbon fiber reinforced polymer (CFRP) and glass fiber reinforced polymer (GFRP), are frequently employed for retrofitting owing to their superior strength-to-weight ratio and simple installation. Natural fibers, such as kenaf, have been increasingly incorporated into fiber reinforced polymer (FRP) composites as sustainable alternatives in the construction industry due to their lightweight nature and low carbon footprint. Yet, many investigations focused on synthetic fibers, thus, the purpose of this study is to develop finite element (FE) models for RC beams and columns retrofitted with CFRP, GFRP and kenaf fiber reinforced polymer (KFRP), to examine the impact of natural fibers and comparing the findings with those derived from synthetic fibers. The models consider element types, mesh discretization, solution methodologies, and nonlinearities. Concrete behavior is represented using Concrete Damage Plasticity (CDP), whereas fiber laminates employ the Hashin damage model. The FE model’s load-displacement behavior, ultimate strength, and failure mechanisms were verified against existing experimental and numerical findings. The findings indicate that FRP wrapping substantially enhances the load-carrying capacity of RC beams, with ultimate load increases ranging from approximately 13% for KFRP to 66% for CFRP, whereas the corresponding improvements for RC columns are notably smaller, remaining below 7%. Although KFRP exhibits lower mechanical performance than GFRP and CFRP, its sustainability and cost-effectiveness support its use in applications where environmental and economic considerations are prioritized.