Browse Articles

Human pannexin mutations and their implications in erosive osteoarthritis

Erosive hand osteoarthritis (EHOA) is a chronic joint disease characterized by severe inflammation and degeneration of cartilage and bone tissue. As this disease is multifactorial in nature, the molecular mechanisms that influence its pathogenesis are unclear, leading to a lack of disease-modifying therapies. However, by screening 40 families with a dominant inheritance pattern for EHOA, we identified two independent germline heterozygous mutations that associated with EHOA onset: PANX1 [c.G455A:p.R152H] and PANX3 [c.G71A:p.R24H]. Pannexin 1 (PANX1) and Pannexin 3 (PANX3) are mechanosensitive channel-forming glycoproteins that pass various metabolites and ions such as adenosine triphosphate (ATP) and calcium to regulate numerous physiological and cellular processes including tissue development, cell differentiation, and homeostasis. In this study, we report that electrophysiological recordings, ATP release, and basal dye uptake assays revealed increased channel activity of the PANX1 R152H variant, which led to increased cytotoxicity following long-term expression. In contrast, R24H mutant PANX3 channels exhibited a loss-of-function in mechanically stimulated dye uptake assays. Under stable, moderate expression conditions, this reduction in channel activity was associated with decreased cell growth, whereas overexpression led to increased cell death. In vivo, R24H expression in zebrafish embryos increased apoptosis and upregulation of p21 and osteogenic genes. Together these findings demonstrate that two mutations with opposing alterations in PANX channel activity, hyperactivity in R152H PANX1 and loss-of-function in R24H PANX3, can converge on degenerative cellular outcomes. Collectively, we report the first germline PANX3 mutation associated with disease and provide the first evidence linking PANX1 and PANX3 mutations to human erosive osteoarthritis.

Structural, optical, electrical conductivity, and thermal properties of some mononuclear and mixed metal complexes of diethyldithiocarbamate

Abstract This study aims to synthesize and characterize a series of mononuclear and mixed metal diethyldithiocarbamate complexes containing Ag(I), Cu(II), Mn(II), and selenium ions, and to explore their structural, optical, electrical, and thermal properties. These complexes are of considerable interest because metal dithiocarbamates can serve as versatile single-source precursors for the fabrication of semiconductor materials and other advanced functional systems. The synthesized complexes were characterized using XRD, elemental analysis (SEM–EDX), spectroscopy techniques (IR, NMR, UV–Vis, ESR, and fluorescence), magnetic measurements, density functional theory (DFT), and thermal analyses (TGA, DTA, DSC). Structural investigations confirmed the ability of diethyldithiocarbamate ligands to form multinuclear coordination assemblies with the investigated metal ions, producing sponge-like structures. The UV–visible spectra showed strong absorption at 240–435 nm and high transmission (84%-99%) around 300 nm, with an optical band gap between 1.95 and 4.15 eV. The oscillator and the dispersion energies of linear refractive index ( n ) were evaluated using the Wemple Di-Domenico single oscillator model. The emission spectra exhibited three fluorescence peaks in the range 427–531 nm. The dielectric characteristics and alternating current conductivity (σ ω ) were measured at temperatures ranging from 298 to 400 K and frequencies between 120 Hz and 100 kHz. The electrical measurements of the samples revealed semiconducting behavior with σ ω values of 10 –7 –10 –1 S/m, and E a of 0.035–2.71 eV. Various conduction mechanisms were observed with increasing temperature, as evidenced by changes in the dielectric parameters. Thermal analyses emphasized that complexes may be applied for the synthesis of nanoscale metal sulfides with semiconductor properties.

Superconductivity suppression and bilayer decoupling in Pr-substituted YBa ₂ Cu ₃ O _{7− <i>δ</i>}

The mechanism behind superconductivity suppression induced by Pr substitutions in YBa 2 Cu 3 O 7− δ (YBCO) has been a mystery since its discovery: in spite of being isovalent to Y 3+ with a small magnetic moment, it is the only rare-earth element that has a dramatic impact on YBCO’s superconducting properties. Using angle-resolved photoemission spectroscopy (ARPES) and DFT+ U calculations, we uncover how Pr substitution modifies the low-energy electronic structure of YBCO. Contrary to the prevailing Fehrenbacher–Rice (FR) and Liechtenstein–Mazin (LM) models, the low-energy electronic structure contains no signature of any f -electron hybridization or additional f -state Fermi surface sheets. Yet, strong electron doping is observed primarily on the antibonding Fermi surface. Meanwhile, we reveal major electronic structure modifications to Cu-derived states with increasing Pr substitution: a pronounced CuO 2 bilayer decoupling and enhanced hopping along the CuO chain, implying indirect electron-release pathways beyond simple 4 f state ionization. Our results challenge the long-standing FR/LM mechanism, and establish Pr substituted YBCO as a potential platform for exploring correlation-driven phenomena in coupled 1D–2D systems.

Genomic insights into the medieval cultivation history of influential high-yielding Asian rice

Inside-out-engineered CuO _x /Ru sites for efficient electrochemical nitrate reduction to ammonia

Electrochemical nitrate reduction reaction (NO 3 − RR) provides a sustainable approach for both NO 3 − purification and NH 3 production. Ru-based catalysts hold great promise for NO 3 − RR, but are limited by competing hydrogen evolution reaction, insufficient electrochemical stability, and the sluggish thermodynamics and kinetics of the initial *NO 3 → *NO 2 reduction step. Here, we develop an inside-out strategy by integrating ultrasmall Ru nanoparticles on the outer surface of carbon nanotubes and confined amorphous CuO x nanowires inside (CuO x @CNT/Ru) to enhance NH 3 synthesis from NO 3 − RR. This catalyst achieves a leading NH 3 yield rate of 146.37±3.4 mg h −1 mg cat −1 at −0.7 V vs. reversible hydrogen electrode (vs. RHE), a Faradaic efficiency of 99.1 ± 0.9% at 0 V vs. RHE, and the highest energy efficiency of 43.5 ± 0.9% at 0 V vs. RHE. Moreover, as a Zn−NO 3 − battery cathode, CuO x @CNT/Ru delivers a maximum power density of 22.6 mW cm −2 along with high NH 3 production efficiency. In situ spectroscopic analysis and theoretical calculations reveal that Ru species serve as the main active centers, while high-valence CuO x not only stabilizes and activates Ru sites but also facilitates the conversion of *NO 3 to *NO 2 and promotes active hydrogen generation from water dissociation, thereby accelerating the hydrogenation kinetics of nitrogen-containing intermediates and reducing the energy barrier of the rate-determining step of *NO to *NOH, ultimately boosting NH 3 synthesis. This work provides an efficient strategy for modulating active site interactions to promote sustainable nitrate reduction processes.

Oncolytic vaccinia virus JX-594 shows subtype-specific activity and candidate biomarkers in gastric cancer cell lines

ICMT supports BRAF ^V600E -driven tumor growth by membrane targeting of the CAAX protein INPP5E

Isoprenylcysteine carboxyl methyltransferase (ICMT) catalyzes C-terminal methylation of prenylated CAAX proteins, a final processing step promoting membrane association and signaling. Although ICMT has been pursued to disrupt RAS membrane targeting, its role in BRAF V600E -driven cancers and critical substrates remains unclear. Here, genetic and pharmacologic (UCM-1336) ICMT inhibition suppressed proliferation and invasion in BRAF V600E -mutant melanoma cells and reduced tumor growth in xenografts and mice. ICMT knockdown inhibited proliferation of BRAF-inhibitor-resistant melanoma cells. We identify INPP5E as an ICMT-dependent substrate: ICMT inhibition reduced INPP5E methylation, displaced it from membranes, and increased PI(4,5)P 2 . Forced INPP5E membrane targeting partially rescued growth defects caused by ICMT inhibition. These findings implicate an ICMT-INPP5E-axis that supports BRAF V600E -driven tumor growth.

Climate resilience mechanisms of vernacular dwellings in China’s Yangtze River delta region: a study based on a multi-level analytical framework

Profile of Richard Robson, Susumu Kitagawa, and Omar M. Yaghi: 2025 Nobel laureates in Chemistry

The 2025 Nobel Prize in Chemistry honors Richard Robson, Susumu Kitagawa, and Omar M. Yaghi for establishing metal-organic frameworks (MOFs) as a new class of crystalline porous materials and, more broadly, for transforming how chemists design extended matter. Their work showed that solids could be built from well-defined inorganic and organic components with unusual control over structure, porosity, and function. This profile highlights the distinct and complementary contributions of the three laureates, from the conceptual foundations of network design to the demonstration of permanent porosity and the development of reticular chemistry. It also examines the broader scientific legacy of MOFs, including their impact on catalysis, separations, sustainability, and modern data-driven materials discovery.

The determination of cultivated soil quality within a semi-humid climate using integrated quality index model and prediction with artificial neural network

Predicting rates of manganese oxide reduction from thermodynamic driving forces and structural properties

Manganese (oxyhydr)oxides are abundant redox-active minerals that influence diverse biogeochemical processes, yet their redox reactivity remains poorly understood due to variations in mineral structure and manganese oxidation state. We quantified the reduction kinetics of three geochemically relevant manganese oxides—birnessite, manganite, and hausmannite—using extracellular electron shuttles with varying redox potentials to systematically modulate the driving force for electron transfer. While the Gibbs free energy ( Δ r G ) described the kinetics of individual oxides well, the Pourbaix free-energy difference ( Δ Ψ ) offered a distinct advantage by predicting reactivity without requiring detailed knowledge on reaction pathways, making it especially valuable for systems where exact redox reactions are undefined. We further developed a coupled kinetic-mass transport model, which showed that electron-transfer rate constants varied among oxides, whereas mass-transfer coefficients were similar. Classical nucleation theory was applied to contextualize these differences, indicating that the balance between surface and bulk energies controls the dissolution barrier. Our findings not only demonstrate how reaction thermodynamics and phase differences jointly control manganese oxide reduction kinetics but also support a generalizable predictive framework for the reactivity of redox-active minerals across diverse environmental conditions.

Short-term vaginal prasterone therapy induces steroid receptor modulation and extracellular matrix remodeling in human vaginal mucosa

Abstract Prasterone (dehydroepiandrosterone, DHEA) is increasingly used in the treatment of genitourinary syndrome of menopause (GSM), although its molecular effects on vaginal tissue remain insufficiently characterized. This prospective study evaluated the short-term impact of vaginal prasterone on steroid receptor expression, epithelial morphology, extracellular matrix composition, and the proteomic profile of the vaginal mucosa. Ten women aged 41–67 years received intravaginal prasterone (6.5 mg daily) for eight weeks. Vaginal biopsies were obtained before and after treatment, and serum estradiol and DHEA-S levels were assessed. Immunohistochemical analysis demonstrated a significant increase in cumulative ERα expression across epithelial layers ( p  = 0.0379), with the most pronounced changes in the superficial epithelium and stromal compartment. Progesterone receptor expression showed stromal upregulation accompanied by epithelial downregulation. Epithelial thickness increased by 17.5 μm following therapy. Proteomic analysis using LC–MS/MS identified 87 proteins with altered abundance, including enrichment of extracellular matrix components and upregulation of collagen IV (COL4A1 and COL4A2). In contrast, several inflammation- and remodeling-related proteins, including IL18, LCN2, SERPINE2, and PRSS27, were downregulated. These findings indicate that short-term vaginal prasterone therapy promotes steroid receptor modulation and extracellular matrix remodeling in human vaginal mucosa while reducing inflammatory signaling pathways. Patient-reported outcomes assessed using the WHOQOL-BREF questionnaire indicated a trend toward improvement in quality of life following treatment, with the largest median increases observed in the physical (Domain 1) and environmental (Domain 4) domains. However, these changes did not reach statistical significance ( p  &gt; 0.05), and no significant differences were observed in overall quality of life or perceived health status.

Rapid sensing and relaying of cellular hyperosmotic stress signals via RAF–SnRK2 core condensates

Hyperosmolarity caused by drought, high salinity, or cold stress inhibits plant growth and crop productivity. A conserved protein-kinase cascade of cytosolic B-RAFs and SnRK2s is rapidly activated upon osmotic stresses to initiate downstream adaptive responses, which represents one of the fastest known responses to osmotic stress in plants. How the kinase cascade is activated by osmotic stress is unknown. Here, we show that Arabidopsis B4 subgroup RAFs have intrinsically disordered regions and directly sense both ionic and nonionic hyperosmolarity by reversible condensation. B4-RAFs recruit and cocondense with subclass-I SnRK2s to phosphorylate and turn on SnRK2s, evading the noncondensable inhibitory A-clade PP2C phosphatases. This straightforward osmosensing and relaying module can be fully reconstituted in Escherichia coli by coexpressing three components or in solution in a test tube using recombinant proteins. Our findings identify B-RAFs as the chief cellular osmosensors that detect low water potential by cocondensation, forming a signal hub with SnRK2s to orchestrate adaptive responses in plants, and represent an evolutionarily conserved osmosensing mechanism across kingdoms.

Wavelet-enhanced spatiotemporal connectivity-preserving network for intracranial artery segmentation in DSA sequences

Abstract Accurate intracranial artery segmentation from Digital Subtraction Angiography is critical for the diagnosis and interventional treatment of cerebrovascular diseases. However, traditional methods struggle to capture dynamic spatiotemporal dependencies, often leading to vascular discontinuity and the loss of fine distal vessels due to background interference and resolution loss. In this study, we propose the Wavelet-Enhanced Spatiotemporal Connectivity-Preserving Network (WESCP-Net), a novel framework designed to synergize physical priors with frequency-domain feature extraction. Specifically, we introduce a Physically-Guided Spatiotemporal Enhancement module that explicitly exploits hemodynamic flow variance to differentiate active vascular signals from static artifacts. To address the loss of high-frequency spatial details in standard downsampling, we incorporate a Wavelet-Integrated Encoder and a Topology-Aware Reconstruction module, which utilize discrete wavelet transforms to preserve sharp vessel boundaries and restore structural connectivity. Experimental results on the DIAS dataset demonstrate that WESCP-Net achieves state-of-the-art performance, yielding a Dice Similarity Coefficient of 0.7982 and an Intersection over Union score of 0.6422. Notably, its connectivity-preserving mechanism achieves a clDice metric of 0.7135, improving the continuity of vascular terminals. WESCP-Net provides a robust technological paradigm for precise cerebrovascular segmentation, facilitating reliable surgical navigation and quantitative diagnosis.

Highlighting a science strategy for human exploration of Mars

Correction: The association between amyloid-beta deposition on dual-task gait performance is partially moderated by cognitive functions in healthy older adults

Dpp and immune response pathway factors mediate paracrine induction of senescent cells in <i>Drosophila</i>

Transition toward senescence is a cellular response to various forms of stress. This phenomenon is evolutionarily conserved across species, from insects to humans. Senescent cells (SCs) permanently withdraw from the cell cycle and undergo physiological changes, notably the acquisition of a robust secretory activity characterized by the release of numerous molecules, including cytokines, chemokines, and metalloproteinases. Through this program, termed Senescence-Associated Secretory Phenotype, SCs communicate with and influence their microenvironment. In mammalian tissues, the number of SCs increases with age and their accumulation has been proposed to contribute to age-associated pathologies. Studies in vertebrate systems have demonstrated that new SCs can arise through paracrine signaling from preexisting SCs, a process that requires the activity of the Transforming Growth Factor β (TGF-β). We have investigated the occurrence of paracrine recruitment of SCs in the fruitfly Drosophila . Our results show that an initial stress event induces a primary wave of SCs, comprising approximately 10% of the cell population. Subsequently, a second wave of SCs emerges through paracrine signaling from the initial cohort, increasing the overall proportion of SCs to about 24%. The formation of this second wave is mediated by the growth factor Decapentaplegic (Dpp), a Drosophila ortholog of the TGF-β superfamily. Dpp activates a noncanonical signaling route in non-SCs, driving their conversion to a senescent state. This branch of the Dpp pathway engages components of the innate immune response. Collectively, these findings underscore the evolutionary conservation of senescence-associated signaling networks and suggest that paracrine amplification of senescence may play a role in tumorigenesis.

Unlocking high-intensity performance thresholds through ventilatory signatures in the ECG

Abstract A ubiquitously available and accurate non-invasive ventilatory threshold assessment (NIVA) would substantially improve real-world performance assessment evaluation in both clinical and elite sports settings. We hypothesised that ECG-derived ventilatory phase analysis achieves reference-standard accuracy for second ventilatory threshold (VT2) determination. 74 healthy adults performed stepwise cardiopulmonary exercise testing with simultaneous lactate sampling to retrieve VT2 and lactate-based (Dmax; LT2) thresholds. Threshold agreement was evaluated for heart rate (HR) and exercise load (W) between VT2, LT2, age-estimated HR (HR-Est) and NIVA. In 66 assessable datasets, NIVA and VT2 yielded equivalent threshold estimates for HR (− 0.46 bpm; 90% CI [− 2.10;1.17]) and exercise load (0.46 W; 90% CI [− 2.35; 3.27]). VT2 and HR-Est diverged (HR − 7.22 bpm, p  &lt; 0.001; load − 6.26 W; p  &lt; 0.001). LT2 was available in 58 subjects and differed from both VT2 ( p  &lt; 0.001) and NIVA ( p  &lt; 0.001). Correlations supported these findings, with close associations between VT2 and NIVA (HR r  = 0.84; load r  = 0.96). NIVA derived a high-intensity performance threshold from ECG signals with reference-standard fidelity and showed close agreement with CPET-derived VT2. Its performance and accessibility make it attractive for frequent reassessment of a VT2-aligned threshold without the need for spiroergometry or lactate measurements. Validation across devices, protocols, populations, and real-world signal conditions is warranted.

Directly adopting inverse biosensors to image live cell enzyme activities in nanodomains

Many biochemical pathways can be monitored by outfitting molecular switches with reporting mechanisms such as fluorescence. The output of these biosensors can either increase or decrease upon target activation. Both types can report average relative changes in time. But a naïve imaging of inverse biosensors, which gives readout decrease, will form nonsensical images by giving low values to both the background and foreground. Thus, currently, superresolution enzyme activity imaging cannot follow the actions of those enzymes that require inverse biosensing. This is a significant obstacle for understanding the ways cells organize their signaling via nanodomains and compartments. We break this barrier and rationally develop a genetically encoded principle to quantify inverse biosensors at superresolution. We generate 3 distinct readout pairs and systematically illustrate previously hidden insights on 3 dynamic signaling hubs.

Tissue transcriptional programs stratify Crohn’s disease by therapeutic response and clinical outcomes