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Olfactory dysfunction is a debilitating yet under-investigated sequela of ischemic stroke, for which no approved pharmacological intervention currently exists. Despite the documented ethnomedicinal use of Lantana camara L. in Cameroon for post-stroke impairments, its neuroprotective potential against ischemia-induced olfacto-mnemonic axis damage remains unexplored. To establish a reproducible rat model of post-stroke olfactory dysfunction and evaluate the neuroprotective effects of an aqueous extract of L. camara (AELC) against global cerebral ischemia-reperfusion-induced olfacto-cognitive deficits. A modified transient global cerebral ischemia-reperfusion model was developed in male Wistar rats via bilateral common and internal carotid artery occlusion. Animals were treated with AELC (140, 280, and 560&#x202f;mg/kg), minocycline (100&#x202f;mg/kg), or piracetam (250&#x202f;mg/kg) as reference compounds. Evaluations encompassed neurological recovery, thermoregulatory profiling, olfacto-cognitive behavioral testing, and biochemical and histological analyses of the olfactory bulb, piriform cortex, prefrontal cortex, and hippocampus. Mechanistic insights were sought through LC-MS phytochemical profiling, in silico ADMET analysis, and curvature-based blind molecular docking against the &#x3b1;7 nicotinic acetylcholine receptor (nAChR; PDB: 7KOX). Ischemia-reperfusion induced severe thermoregulatory failure, locomotor deficits, and significant olfactory dysfunction (Hedges' g > 2.00), correlating with acetylcholine depletion, oxidative stress (elevated MDA and nitrites; depleted GSH), and neuroinflammation (elevated IL-1&#x3b2; and TNF-&#x3b1;). Histological examination confirmed significant neuronal pyknosis, ghost cell formation, and architectural disorganization across the olfacto-mnemonic axis. AELC at 280 and 560&#x202f;mg/kg effectively reversed these deficits, restoring cholinergic tone (p&#x202f;<&#x202f;0.001) and preserving neuronal microarchitecture comparably to reference compounds. LC-MS and in silico analyses identified Salvigenin and Kigelinone as promising bioactive leads with favorable drug-likeness and high predicted membrane permeance. Kigelinone exhibited predicted binding interactions at a site topographically consistent with known allosteric modulators of &#x3b1;7 nAChR, forming a hydrogen bond with Ala262 of the M2 transmembrane helix, a mechanistic hypothesis warranting functional validation. These findings establish a reliable rat model of post-stroke olfactory dysfunction and demonstrate that L. camara confers significant neuroprotection by modulating the cholinergic-antioxidant-neuroinflammatory axis, validating its ethnomedicinal use and offering a promising natural scaffold for the development of targeted therapeutics against ischemic brain injury.

The current treatment of rheumatoid arthritis (RA) remains limited by severe drug-associated side effects and poor suppression of bone erosion. Herein, we report the development of biomimetic nanoparticles (CEC NPs) that co-deliver celecoxib (CXB) and the lysine-specific demethylase 1 (LSD1) inhibitor CC-90011 via M2 macrophage-derived exosomes (M2 Exos), thereby integrating targeted delivery with innovative multi-mechanistic therapeutic strategies. The M2 Exos enable innate homing to inflamed synovium and osteoclast-rich lesions, while ensuring efficient intracellular delivery. CEC NPs combined repolarize macrophages from the M1 to M2 phenotype, suppress fibroblast-like synoviocyte activation, and critically inhibit bone erosion by blocking the LSD1-NFATc1 signaling pathway in the osteoclast. Collectively, these effects result in potent anti-inflammatory and osteoprotective outcomes. Notably, we identified CC-90011 as a previously unrecognized anti-erosive agent to directly suppress bone erosion in RA treatment. In a collagen-induced arthritis (CIA) model, CEC NPs markedly outperform monotherapies, with pronounced reduction in joint swelling, cartilage degradation, and bone erosion, without systemic toxicity. This work introduces an M2 Exo-based dual-drug delivery system as a versatile strategy for multi-mechanistic modulation of inflammation and bone destruction, offering a promising paradigm that could be extended to other inflammatory and autoimmune bone disorders.

High water table and anoxic conditions are the major drivers of the development of tropical peatlands. However, land-use change and degradation have severely disrupted their greenhouse gas exchange dynamics. Here, we synthesized published evidence to compare methane (CH4), carbon dioxide (CO2), and nitrous oxide (N2O) fluxes between natural and degraded tropical peatlands and to evaluate their associations with hydrological, climatic, and soil variables. We found that degradation significantly reduced CH4 emissions and increased N2O emissions from peatlands. CO2 emissions did not differ between natural and degraded from tropical peatlands. Water table emerged as an important factor regulating N2O emission, while CH4 and CO2 emissions were significantly correlated with pH and soil carbon-to-nitrogen (C/N) ratio. These patterns represent synthesis-level associations, rather than direct mechanistic proof, because the datasets combine diverse land-use types and management histories. Our review highlights that greater attention should be directed toward the effect of drainage, fertilizer inputs, and fire events on tropical peatlands.

Breast cancer remains a significant clinical challenge, with treatment failure and patient mortality primarily attributable to tumor metastasis. Daucosterol linoleate (DL) was previously isolated from sweet potato (Ipomoea batatas). Using HPLC analysis of ten commercial dried sweet potato products from different regions of China, DL was detected in all samples, with concentrations ranging from 1.24&#xa0;mg to 6.05&#xa0;mg per 100&#xa0;g, confirming its widespread presence in commercially processed sweet potato products. Pharmacokinetic analysis showed that DL exhibited a peak plasma concentration (Cmax) of 1452.28&#xa0;ng/mL, an elimination half-life (t1/2) of 11.14&#xa0;h, and a mean residence time (MRT) of 9.62&#xa0;h, supporting its potential for oral administration. DL significantly suppressed proliferation and migration of MCF-7, 4T1, and MDA-MB-231 cells in vitro and reduced lung metastasis in vivo. Proteomic analysis identified SCD1 as a key molecule mediating the effects of DL. Mechanistically, DL downregulated SCD1 to inhibit epithelial-mesenchymal transition (EMT), as evidenced by decreased expression of N-Cadherin, MMP2, Vimentin, and Snail, alongside increased E-Cadherin expression. Collectively, DL inhibits breast cancer metastasis by downregulating SCD1 and suppressing EMT, supporting its dual potential as a functional food ingredient and adjuvant therapeutic.

Notoginseng Radix et Rhizoma (NRR), derived from Panax notoginseng, serves as both a functional food and a key medicinal material in traditional Chinese medicine. Its bioactivity is largely attributed to saponins, which undergo significant chemical transformations during processing (e.g., steaming), altering its pharmacological profile. This review aims to systematically consolidate experimentally verified metabolites from authenticated NRR, elucidate the chemical transformations induced by processing and clarify the resulting shift in pharmacological effects, thereby providing a scientific basis for its targeted application. A comprehensive literature search was conducted using CNKI, Wanfang Data, National Science and Technology Library, the Pharmacopoeia of the People's Republic of China, PubMed and Web of Science. Keywords included Panax notoginseng (Burk.) F. H. Chen; Pharmacological activities; Phytochemisity; Saponin transformation; Traditional processing; Traditional Chinese medicine. Data were also sourced from classic texts, dissertations and unpublished materials. Processing, particularly steaming, converts high-polarity saponins into less polar ones via deglycosylation, dehydration and hydroxylation. This chemical shift underlies a functional transition: raw NRR primarily promotes blood activation and stasis dispersion, while processed NRR exhibits enhanced blood-nourishing, antioxidant, anti-inflammatory and immunomodulatory activities. The integration of ethnopharmacological knowledge with modern scientific perspectives clarifies the metabolite pathways and mechanistic basis for processing-induced changes in NRR. This review provides a reliable foundation for the precise use and further development of NRR in functional foods, nutraceuticals and evidence-based therapy.

Fusarium proliferatum TQN5T is an endophytic fungus isolated from Dysosma versipellis in Tuyen Quang, Vietnam. The genome assembly comprised 443 contigs totalling 47.7 Mb (46.26% GC content, N50: 509,240 bp) with a completeness score of 96.35%. The draft genome contained 14,299 predicted genes (average length 1516.61 bp), along with 339 tRNAs and 84 rRNAs. Genome annotation revealed 1224 CAZy genes with predominant glycoside hydrolases and 60 secondary metabolite biosynthetic clusters (smBGCs) enriched in T1PKS and terpene types, including bioactive compound clusters such as &#x3b1;-acorenol. This genomic dataset provides essential information to support future mechanistic studies of PTOX biosynthesis and cytotoxic activity in F. proliferatum TQN5T.

TBL1XR1 is frequently mutated in diffuse large B-cell lymphoma (DLBCL), yet its functional impact on tumor microenvironment remains poorly defined. In this study, we characterized TBL1XR1 mutations in a cohort of 1842 newly diagnosed DLBCL patients, identifying mutations in 9.4% of cases (n&#x2009;=&#x2009;173). These mutations correlated with clinically aggressive features, including older age (>&#x2009;60 years), high-risk International Prognostic Index, enrichment in non-GCB subtypes, as well as inferior progression-free and overall survival. Mechanistically, TBL1XR1 mutations enhanced H3K27ac levels at the MYC promoter, increased MYC expression and subsequently up-regulated its immune-regulatory targets CD47 and PD-L1. This axis impaired natural killer (NK) cytotoxicity, facilitating immune escape and tumor progression. In a murine A20 B-lymphoma model, tumors harboring Tbl1xr1 mutations exhibited up-regulated MYC, CD47, and PD-L1 expression, resulting in NK cell dysfunction and tumor growth acceleration via the MYC-CD47/PD-L1 axis. Dual blockade of CD47 and PD-L1 restored NK cell-mediated tumor immunity, triggering rapid regression of Tbl1xr1-mutated tumors. Taken together, our findings identified TBL1XR1 mutations as a microenvironment-related mechanism of DLBCL progression and provided clinical rationale of co-targeting CD47 and PD-L1 to treat this genetically defined subset.

The stratum corneum is the principal barrier limiting topical delivery of hydrophilic molecules. We hypothesized that high-pressure microjet (HPMJ) systems would enhance epidermal deposition without breaching the dermis. The efficacy of a handheld HPMJ device (K-Stream) for epidermal drug delivery was evaluated in: (i) Ex vivo human skin explants treated with Lucifer Yellow, with dye distribution quantified in the stratum corneum, suprabasal, and basal layers by fluorescence microscopy, (ii) Ex vivo caffeine penetration assessed by confocal Raman spectroscopy with depth-resolved mapping of caffeine-specific spectra, and (iii) A randomized, split-face, 14-day in vivo trial (n&#x202f;=&#x202f;23) comparing changes in stratum corneum hydration after twice-daily application of serum via HPMJ or manual massage. In the ex vivo fluorescence study, HPMJ application increased Lucifer Yellow in the suprabasal layers by up to approximately 4-fold versus manual application (e.g., +412% at 6&#x202f;h, p&#x202f;<&#x202f;0.01). Raman spectroscopy demonstrated at 4&#x202f;h caffeine signal was confined to the outermost &#x223c;20&#x202f;&#x3bc;m with manual application, whereas HPMJ produced detectable caffeine spectra down to 60&#x202f;&#x3bc;m without signal in the dermis. In vivo the HPMJ-treated side exhibited a significantly greater and faster hydration over 14 days. At day 14, hydration on the HPMJ side exceeded the manual side by &#x223c;6 units (p&#x202f;=&#x202f;0.003). No treatment-related adverse events were observed. HPMJ increases epidermal delivery depth and functional hydration relative to manual application of the same formulation. These data support HPMJ as a non-invasive platform for enhancing epidermal delivery of hydrophilic actives, while highlighting the need for larger, mechanistic studies.

The development of multifunctional luminescent nanomaterials for environmental monitoring and wastewater remediation has attracted considerable research interest. In this work, Eu3+-activated NaGd(MoO4)2, NaGd(WO4)2, and Na3Gd(VO4)2 nanophosphors were hydrothermally synthesised and subsequently functionalized with 4,4'-bipyridyl (4,4'-bipy) to establish dual-mode photoluminescent sensing and photocatalytic platforms. Structural and morphological analyses confirmed the formation of highly crystalline rod-like nanostructures with successful surface functionalization. Among the synthesised materials, Na3Gd(VO4)2:Eu3+@4,4'-bipy exhibited the highest emission intensity and longest decay lifetime (3.16 ms), indicating efficient energy transfer and suppressed non-radiative relaxation pathways. The functionalized nanophosphors demonstrated concentration-dependent turn-off photoluminescence sensing behaviour toward Cr3+ ions. Notably, Na3Gd(VO4)2:Eu3+@4,4'-bipy showed superior sensing performance with a Stern-Volmer constant of 8.2 &#xd7; 104 M-1 and a detection limit of 0.017 ppm. Furthermore, the quenched emission was effectively restored using chelating agents, particularly trisodium citrate, establishing a reversible dual-mode OFF-ON photoluminescent sensing system with a recovery efficiency of &#x223c;92.6%. Mechanistic investigations suggested that the turn-off sensing process is primarily governed by photoinduced electron transfer (PET) and luminescence resonance energy transfer (LRET) interactions, whereas the turn-on emission recovery process is associated with trisodium citrate-assisted chelation of Cr3+ ions. In addition, NaGd(WO4)2:Eu3+@4,4'-bipy exhibited superior photocatalytic activity toward Rhodamine B degradation under UV irradiation owing to its lower bandgap energy and enhanced light absorption capability. These findings highlight the potential of rare-earth-functionalized nanophosphors for selective ion sensing, emission recovery, and environmental remediation applications.

Osteoarthritis (OA) is a common degenerative joint disorder and there are currently no effective therapies to impede its destructive progression. Astragaloside IV (AS-IV), a natural compound, exhibits promising chondroprotective effects, yet its specific molecular mechanisms remain poorly clarified. Thus, this study employed transcriptomic profiling combined with bioinformatics analysis to identify OA-related characteristic genes, and further conducted experiments to verify the potential therapeutic mechanism of AS-IV. Analysis of the GSE114007 dataset was performed using False Discovery Rate (FDR)-adjusted p-values and quantile normalization to mitigate batch effects. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key modules. Nine OA-related feature genes were identified and validated in two external datasets (GSE129147 and GSE51588) using LASSO with 10-fold cross-validation and a random forest algorithm to minimize the risk of optimistic bias. Furthermore, gene set enrichment analysis (GSEA) was conducted. The underlying mechanisms were validated through molecular docking, cellular thermal shift assay (CETSA), as well as in vitro experiments using ATDC-5 cells and in vivo assays with OA mice. We identified 1548 differentially expressed genes (DEGs) primarily enriched in the extracellular matrix, with PI3K-Akt signaling closely related to OA. The MEBlack module was strongly associated with OA (cor = -0.79, p<0.0001). GSEA showed the feature genes were associated with the adipocytokine signaling pathway and glycosaminoglycan biosynthesis. Furthermore, molecular docking and CETSA indicated that ETS2 served as a potential interacting target of AS-IV. In the destabilization of the medial meniscus (DMM)-induced OA mice, the results of Safranin O/Fast Green staining confirmed that AS-IV alleviated cartilage loss and lowered OARSI scores. Mechanistically, AS-IV slowed OA progression by upregulating Col2a1 expression, suppressing MMP13 levels, and reducing inflammatory markers such as IL-1&#x3b2; and TNF-&#x3b1;. Importantly, AS-IV enhanced ETS2 expression in osteoarthritic chondrocytes. Consistently, in vitro functional assays revealed that knockdown of ETS2 in chondrogenic ATDC-5 cells partially reversed both the chondroprotective and anti-inflammatory effects of AS-IV, verifying the essential role of ETS2 in mediating the therapeutic effects of AS-IV against OA. Collectively, these findings point to the vital function of ETS2 in OA pathogenesis and demonstrate that AS-IV attenuates cartilage degradation and inflammatory responses by upregulating ETS2, thereby retarding OA development.

Pancreatic cancer remains one of the most treatment-refractory malignancies, displaying profound resistance to chemotherapy and radiotherapy. While the benefit of photon radiotherapy remains debated, heavy-ion modalities such as carbon ions show promise in overcoming radioresistance. Here, we extend this paradigm by evaluating oxygen-ion beam irradiation in pancreatic cancer cells and directly comparing its efficacy with carbon ions and photons. Oxygen ions induce higher clonogenic cell killing in human pancreatic cancer cells, with a relative biological effectiveness (RBE) around two times higher for oxygen ions than for carbon ions. Moreover, their growth-inhibitory effects are substantially less dependent on gemcitabine-mediated radiosensitization than those of carbon ions or photons. Mechanistically, oxygen-ion irradiation induces greater direct and complex DNA damage, slows down DNA repair kinetics, and augments apoptosis following combined gemcitabine treatment, accompanied by sustained activation of DNA damage response pathways. These findings delineate the distinct radiobiological advantages of oxygen ion beam irradiation in pancreatic cancer and highlight their potential as a powerful modality to overcome radioresistance, providing a compelling rationale for further translational and clinical exploration.

Primary cilia are highly specialized, solitary microtubule-based organelles widely present on the surface of mammalian cells. Acting as integrative platforms for membrane-associated signaling and intracellular pathways, primary cilia regulate Hedgehog (Hh), Wnt, G protein-coupled receptor (GPCR), and mTOR signaling and are closely implicated in metabolic dysregulation associated with type 2 diabetes (T2D). This review systematically summarizes current methodological approaches for studying primary cilia and delineates their pathogenic roles in T2D from multiple dimensions. In the central nervous system, hypothalamic primary cilia regulate appetite and energy expenditure through ADCY3/MC4R and BBSome modules. In peripheral metabolic organs, primary cilia in adipose tissue, liver, and bone influence cellular differentiation, lipid metabolism, and insulin sensitivity. In pancreatic islets, primary cilia on &#x3b1;, &#x3b2;, and &#x3b4; cells coordinate hormone secretion and vascular remodeling via GPCR-cAMP, Somatostatin-SSTR3-GLI2, and Eph/Ephrin signaling pathways. Ciliopathy-associated genetic disorders and defects in centrosomal proteins further substantiate the pathological association between primary ciliary dysfunction and T2D. In addition, the identification of primary cilia-related biomarkers, together with therapeutic explorations involving MC4R agonists, GLP-1 receptor agonists, and mutation-targeted repair strategies, provides a rationale for the clinical translation of cilium-targeted interventions. Collectively, primary cilia may function as central hubs for integrating metabolic signals, regulating intercellular communication, and maintaining energy homeostasis. Future studies should further elucidate cell type-specific differences in primary ciliary receptor localization, signal integration, and secretory regulation; clarify the temporal dynamics of primary ciliary function during development, metabolic stress, and disease progression; and evaluate the structural and functional plasticity of primary cilia, as well as potential therapeutic windows, to facilitate the translation of cilia biology from mechanistic insights to clinical applications in T2D.

Cyclopropylamines have emerged as privileged substrates in photocatalysis owing to their propensity to undergo single&#x2011;electron oxidation followed by strain&#x2011;release &#x3b2;-scission, generating highly reactive distonic iminium radicals. These intermediates underpin a broad repertoire of light-driven transformations, including ring&#x2011;opening functionalization, formal [3 + 2] cycloadditions, radical cascade processes, and asymmetric bond-forming reactions. This Review highlights recent advances in the photochemical activation of cyclopropylamines, emphasizing mechanistic insights, catalyst design, and the synthetic potential of these reactions for accessing complex carbocycles, heterocycles, and medicinally relevant scaffolds. This review is organized to first summarize the preparation of cyclopropylamine derivatives, then to discuss their photoinduced rearrangements and ring&#x2011;opening pathways, followed by an overview of [3 + 2] cycloadditions, enantioselective strategies, and applications for constructing unconventional building blocks. Together, these developments underscore the growing impact of cyclopropylamine-derived radicals as versatile tools in modern synthetic methodology.

Intrinsically disordered proteins (IDPs) and regions (IDRs) challenge the classical structure-function paradigm by fulfilling essential biological roles in the absence of a stable three-dimensional fold. Rather than occupying fixed conformations, IDPs exist as dynamic ensembles that enable high-specificity, low-affinity interactions, multivalent regulatory functions, and context-dependent binding across diverse cellular environments. This conformational plasticity underlies their central roles in signaling, transcriptional regulation, chromatin organization, and the assembly of membrane-less organelles through liquid-liquid phase separation (LLPS). The present review offers several conceptual contributions. First, we develop a cross-kingdom synthesis of disorder-based chromatin regulation, demonstrating that bacterial nucleoid-associated proteins, plant transcription factors, and mammalian chromatin regulators share a conserved charge-regulatory logic, mediated by PTM-dependent mechanisms that dynamically couple environmental signals with genome organization. Second, we integrate mechanistically related but frequently siloed disease pathways, including mitophagy dysfunction, oxidative stress signaling, neuroinflammation, and aberrant phase separation, into a unified framework linking IDP conformational dysregulation to neurodegeneration and cancer. Third, we highlight underexplored regulatory dimensions of IDP biology, including proline isomerization and ubiquitylation-driven condensate formation, that influence conformational ensembles and signaling outputs in ways not captured by conventional structural approaches. Finally, we critically evaluate recent advances in AI-assisted disorder prediction and hybrid experimental-computational ensemble characterization, emphasizing both their transformative potential and current limitations. Dysregulation of IDPs underlies a broad spectrum of human pathologies, and we discuss the emerging opportunities and persistent challenges in targeting these conformationally dynamic proteins therapeutically, including through PROTAC-based degraders, condensate modulators, and ensemble-based drug screening strategies.

Dioxygen activation involving transition metal complexes, and its participation in substrate inert bond functionalizations, plays a crucial role in understanding the function of certain metalloenzymes as well as in the development of bioinspired catalysis. Here, we have described a unique module of side-on peroxo dicopper(II) formation using a tridentate alkyl amine ligand and its concomitant participation in benzylic hydroxylation of the internally tethered phenethyl moiety. Structural and spectroscopic characterization authenticates the unsymmetrical trinuclear copper (Cu3) complex as a final product. Moreover, the EPR data and the magnetic moment calculation (1.89&#xa0;B.M.) by the Evans method, together with spin density calculation (including broken symmetry treatments), collectively lead to the consideration of a spin 1/2 system for CuII 3 species. The spectroscopic studies conducted at low temperatures, along with a series of controlled experiments and DFT-calculated transition state analysis, offer valuable insights into the mechanistic details of hydroxylation reaction.