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Transcriptomic insights into exercise-induced trabecular bone microarchitectural adaptations following combined aerobic and resistance training in mice

Abstract Osteoporosis is a prevalent musculoskeletal disorder, rising in incidence and impact as the global population ages. Peak bone mass (PBM), determined by bone mineral density (BMD) during adolescence, is a key determinant of skeletal health and later osteoporosis risk. Exercise enhances BMD, yet its molecular mechanisms remain unclear. This study examined combined exercise effects on bone health in early adult mice using RNA sequencing (RNA-seq) analysis. Nineteen-week-old mice were randomly assigned to control (CON, n=8) or combined exercise (EXE, n=8) groups. The 12-week intervention included aerobic and resistance training, with physical performance tests conducted before and after. Following intervention, tibial bone characteristics were assessed by dual-energy X-ray absorptiometry (DXA) and micro-computed tomography (μCT), while femoral gene expression was analyzed using transcriptomic analysis. EXE mice demonstrated significant increases in grip strength and exhaustion test performance, but not in the rotarod test. Proximal tibial trabecular bone microarchitecture was enhanced in the EXE group, with increased bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N), along with a trend toward reduced trabecular separation(Tb.Sp). Transcriptomic analysis revealed 109 upregulated and 551 downregulated differentially expressed genes. Gene ontology analysis highlighted enrichment of terms related to muscle cell differentiation, contraction, and ion regulation. Bone metabolism-related GO Biological Process terms were specifically enriched, with Pax1 and Dcstamp upregulated and Fgf18, Scx, and Scube2 downregulated. KEGG analysis identified eleven significantly enriched pathways, including Calcium signaling, ECM-receptor interaction, and PI3K-Akt signaling. These findings suggest that combined exercise enhances trabecular bone microarchitecture and induces transcriptomic changes involving genes associated with bone development, remodeling, and extracellular matrix organization, providing molecular-level evidence for exercise-induced skeletal adaptation.

A geometric criterion links HIV-1 capsid topography to its biophysical properties and function

Abstract Mathematical models of virus capsid structure are pillars of modern virology, aiding the understanding of viral mechanisms and the design of antiviral interventions. Traditionally, the HIV-1 capsid core geometry is represented as a fullerene lattice, akin to the icosahedral models of spherical viruses in Caspar-Klug theory. However, recent studies revealed that many viral capsids deviate from such idealised lattices, with important functional implication. Here we show that this is the case also for the conical HIV-1 core geometries, in which the hexamer and pentamer boundaries form a pseudo-tiling rather than a perfectly aligned fullerene network. We introduce a triangular geometric criterion that quantifies local deviations of an HIV-1 atomic model from its idealised fullerene backbone. Using this criterion, we present that this difference in geometric organisation between idealised (fullerene) and actual (data-derived) capsid model has implications for the capsid’s biophysical properties. We also discuss the use of the geometric criterion as a predictive tool regarding cofactor binding and implied geometric changes in the capsid surface coupled to the interfacial frustration response. Our results establish a quantitative framework linking capsid geometry, curvature, and biophysical function, offering new perspectives for assembly inhibitor design and lentiviral vector engineering.

Inside Front Cover: Stable Synapse‐Like Memory Switching in N‐Heterocyclic Carbene Monolayers (Angew. Chem. Int. Ed. 25/2026)

DNA-based identification uncovers the illegal trade of sea cucumbers from Brazil

Abstract The illegal trade of sea cucumbers is widespread, driven by high international demand, particularly in Asia, where they are valued as culinary delicacies and for use in traditional medicine. Although domestic consumption in Brazil is limited, illegal harvesting for export is a growing concern, with unregulated fisheries posing a threat to local populations. In 2023, the Brazilian Institute of Environment and Renewable Natural Resources (IBAMA) seized dried sea cucumber specimens at Guarulhos International Airport. Using DNA barcoding with the Cytochrome C Oxidase I (COI) gene, we identified 18 specimens as Holothuria grisea and 22 as Isostichopus badionotus . Although both species are currently listed as “Least Concern” by the IUCN globally, the unregulated nature of this trade raises concerns about potential overexploitation, especially given the ecosystems they inhabit are increasingly vulnerable to habitat degradation and unsustainable practices. Additionally, the absence of H. grisea sequences in public genetic databases required us to collect fresh specimens to complete the analysis, underscoring the need for expanded molecular repositories. Open access to molecular repositories is a cornerstone of modern scientific progress, serving as a critical infrastructure for collaborative research. By providing unrestricted availability of standardized molecular data, these repositories not only prevent redundant investigations and optimize the use of research resources but also reinforce the robustness and reproducibility of scientific findings through independent validation. Furthermore, this democratization of knowledge levels the scientific playing field, enabling institutions of varying sizes and from diverse geographical locations to contribute equitably to the global research endeavor. Consequently, open access to these databases maximizes the return on public investment in science and significantly accelerates the pace of discovery in critical fields such as drug development and materials science. Our findings highlight the effectiveness of molecular tools in identifying illegally traded species, even in degraded forms, and emphasize the importance of stricter monitoring to protect biodiversity.

Diagnostic challenges and Gram-negative pathogen dominance in early- and late-onset neonatal infection in Manila, Philippines

Enantioselective C–H Functionalization Reactions Enabled by Cobalt(III)‐Centered Chiral Pockets

ABSTRACT Due to the difficulty in achieving stereoselective recognition of three‐dimensional functionalization reagents, desymmetrization and (dynamic) kinetic resolution of such complex architectures via transition‐metal‐catalyzed asymmetric C─H functionalization remains highly challenging. Herein, we develop a novel platform for enantioselective C─H functionalization enabled by trivalent‐cobalt‐centered chiral pockets. It achieves two formidable tasks in stereochemical control: (1) the desymmetrization of prochiral biaryls to access enantioenriched axially chiral molecules, and (2) the kinetic resolution of racemic [2.2]paracyclophanes to construct planar‐chiral architectures. Integrated mechanistic and computational studies allowed us to unravel the intricate details of how the cobalt(III)‐centered chiral pockets achieve precise, substrate‐specific recognition within congested 3D molecular frameworks.

Beyond calories: the role of media pressure and body appreciation in shaping time perception of food cues in female adolescents

Arene difunctionalization through an acyl-inserting Smiles rearrangement enabled by N-heterocyclic carbene catalysis

Abstract Arene difunctionalization offers a powerful strategy for the simultaneous installation of two functional groups in a single step. Despite recent advances, ipso / para -selective arene transformations remain underdeveloped. Herein, we report an N -heterocyclic carbene (NHC)-catalyzed radical protocol that addresses this challenge. The process features a unique generation of acyl-inserting Smiles rearrangement, wherein radical Meisenheimer intermediates are intercepted by NHC-bound radicals prior to rearomatization. Subsequent ketone deprotonation regenerates ionic Meisenheimer intermediates, thereby completing the rearrangement and affording 1,4-difunctionalized arenes. This organocatalytic protocol exhibits broad substrate scope, tolerates diverse functional groups, and delivers acylated aniline derivatives in excellent yields (96 examples, up to 98% yield). The synthetic potential is further showcased by a ring-expansion strategy to benzo[ b ]azepines and by late-stage functionalization of drug-like molecules. Mechanistic insights from combined experimental and computational studies shed light on the unique reactivity and the observed excellent site-selectivity.

Grain protein and yield stability study in rainfed durum wheat RILs

Active nitrogen mediated selective ruthenium migration on ceria for high pressure ammonia decomposition

Abstract Precise stabilization of atomic structures under reaction environments remains a central challenge in heterogeneous catalysis. Here, we demonstrate that ammonia (NH 3 ) serves as a chemically active nitrogen source to derive the selective migration of ruthenium (Ru) atoms onto ceria (CeO 2 ) domains, forming a durable atomically dispersed structure. During ammonia decomposition, nitrogen-containing intermediates promote atomic redistribution of Ru and anchor the atoms selectively at CeO 2 , yielding stable Ru-ceria interfaces. The resulting catalyst exhibits high activity in high-pressure ammonia decomposition for hydrogen production, attributed to its lowered activation energy and mitigated hydrogen poisoning. Furthermore, both the catalytic performance and the atomic Ru structure are preserved during long-term high-pressure operation, confirming the exceptional structural stability of the designed configuration. This study establishes active-nitrogen-driven migration as an effective strategy for constructing robust and reaction-friendly catalyst surface.

Boosting Cobalt Porphyrin for Selective Nitrate Electroreduction

ABSTRACT The electrocatalytic reduction of nitrate (NO 3 − ) to ammonia (NH 3 ) offers a sustainable pathway for NH 3 synthesis. Metal porphyrins are promising electrocatalysts for the NO 3 − reduction reactions (NO 3 RR) due to their tunable molecular structures, yet effective strategies for enhancing their performance are still lacking. Herein, we develop an efficient composite electrocatalyst based on cobalt tetraphenylporphyrin (CoTPP) for electrochemical NH 3 synthesis by mitigating hydroxide (OH − ) interference and optimizing active hydrogen supply. CoTPP is identified as a superior catalyst with a strong affinity for NO 3 − adsorption, and neutral condition is adopted to suppress the competitive OH − adsorption. Poly(benzodifurandione) (PBFDO) is further introduced as an active hydrogen support cocatalyst. The optimized composite catalyst of CoTPP+carbon nanotube (CNT)+PBFDO shows high Faradaic efficiencies (FEs) of NH 3 near 100% across a broad potential range, and a high NH 3 yield rate (5.3 mg h −1 cm −2 ) is achieved, increasing by fivefold when compared to the catalyst without PBFDO. This work provides mechanistic insights into enhancing the activity of molecular electrocatalysts for the conversion of NO 3 − to NH 3 .

Machine learning empowered proactive content caching in O-RAN

Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis

Abstract Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death within this decade. Here, we show that its major driver oncogene KRAS activates the cGAS-STING-TBK1 axis, inducing a type I interferon (IFN) response that primes PDAC cells for necroptosis. Using genetically engineered mouse models, we find that cancer cell-specific deletion of caspase-8 is sufficient to trigger necroptotic cell death, eliminating most pancreatic precursor lesions. Mechanistically, KRAS-driven IFN signalling induces ISGF3-dependent expression of necroptosis-related interferon-stimulated genes, including MLKL. This renders PDAC cells selectively vulnerable to necroptosis upon caspase-8 inhibition. Therapeutically, pharmacologic caspase inhibition reduces tumour burden in aggressive PDAC models and human patient-derived organoids. A pan-cancer transcriptomic analysis links necroptosis gene expression with Ras pathway activity and IFN signatures across multiple tumour types. These findings reveal a KRAS-induced IFN program that sensitises tumour cells to necroptosis, highlighting a therapeutic vulnerability in PDAC with broader relevance across IFN-activated cancers.

Numerical investigation and assessment of the Langmuir–Hinshelwood–Hougen–Watson model for dry reforming of methane

Breaking continuity to prevent catastrophic building collapse

DRQuantum: a drug repurposing method by quantum walks on a multi-layered heterogeneous network

Abstract Traditional drug development poses significant financial and temporal costs, whereas drug repurposing emerges as a cost-effective and efficient alternative. As large-scale biological networks proliferate, computational drug repurposing has become feasible, yet accurately capturing intricate heterogeneous network structures remains a persistent challenge. To address this challenge, we introduced a novel approach, called DRQuantum: Drug Repurposing via Quantum walks. Unlike random walks, quantum walks dispense with independence and harness quantum entanglement to simultaneously explore multiple paths, enabling faster traversal of networks. Moreover, DRQuantum accounts for both the local and global network structures. In this study, we constructed a heterogeneous multi-layer network by integrating drug-drug, disease-disease and protein-protein interaction networks. We then employed quantum walks to learn low-dimensional feature representations of nodes in these heterogeneous networks, ultimately inferring candidate drugs for repurposing beyond their original indications. Consequently, we observed that DRQuantum outperforms traditional drug repurposing methods in terms of AUROC, AUPRC and accuracy. Additionally, case studies for several specific diseases further validate the practical utility of our proposed method.

Transition Radiation Field Enhanced Laser Proton Acceleration Employing Near-Critical-Density Foam

Abstract Laser-driven protons with ultrafast temporal properties attract great interest in fields ranging from flash radiation oncology to compact accelerators. High-efficiency energy coupling of protons from laser-induced accelerating fields is complex, hybrid acceleration mechanisms that combine multiple field contributions prove critical for optimizing proton energy. Here, we report a laser proton acceleration scheme in which proton energy can be enhanced by a transition radiation field (TRF) built by high-energy and large-charged electron bunches. Using near-critical-density plasmas, we experimentally produce electron beams with charges up to ~30 nC (>13 MeV). As these electrons exit the target, they emit intense TRF with energy up to 0.6 J in 0.1-15 THz range, corresponding to an acceleration field of 10 12–13 V m –1 . When superposed with the charge-separation field (CSF), proton cut-off energy is boosted by more than a factor of two, reaching 90 MeV. The resulting spectra exhibit a distinctive plateau-shaped feature in the high-energy regime. Multi-dimensional kinetic simulations confirm the synergistic role of the TRF and CSF in both enhancing the proton energy and shaping the spectral structure. This scheme provides new insights into the coupling between relativistic electron beams and acceleration fields and facilitates more efficient laser-driven proton acceleration.

Radical Anion‐Driven Electron‐Ion Coupled Repair Chemistry for Direct Regeneration of Degraded LiFePO ₄ Cathodes

ABSTRACT Direct regeneration of spent LiFePO 4 (LFP) cathodes is a sustainable alternative to conventional recycling methods. However, poor remediation efficiency and complex processes limit its application. Here, we develop a room‐temperature liquid‐phase strategy based on a deep green lithium naphthalenide (Li‐Naph) solution. This strategy utilizes radical anion‐driven electron‐ion coupling remediation chemistry to integrate electron donors, lithium transport, and surface reconstruction within a single solution‐phase platform. The strongly reducing naphthalene radical anion enables spontaneous electron transfer at ambient conditions, efficiently converting Fe 3+ back to Fe 2+ , while promoting surface lithium enrichment through coupled electron–ion interactions. Subsequent annealing allows the enriched lithium to diffuse into lithium vacancies, while the organic residues undergo in situ carbonization into a conformal conductive shell, achieving synergistic bulk repair and surface reconstruction. This chemistry fully restores the olivine framework, suppresses Fe–Li anti‐site defects, and markedly enhances Li + transport kinetics. The regenerated cathode delivers a high initial capacity of 140.1 mAh g −1 and retains 92% capacity after 650 cycles at 1C, even maintaining excellent stability at a high rate of 5C. Importantly, the strategy remains effective for severely degraded cathodes, highlighting the broad applicability of radical‐anion‐driven repair chemistry.

Boosting targeted adversarial transferability via fine-grained feature mixup perturbation and reference-based gradient refinement

Continuous solar-driven recycling of lithium-ion battery cathode materials enabled by a stable benzobisthiazole-linked polymeric photocatalyst