Local extirpations and extreme bottlenecks can deplete genetic variation and obscure population dynamics, especially in highly mobile species. The gray whale (Eschrichtius robustus) undertakes some of the longest known migrations among mammals, and two stocks (eastern and western gray whales) were historically recognized in the Pacific. Commercial whaling depleted both stocks, and while the Eastern North Pacific (ENP) stock has rebounded, the western stock was feared extirpated. In the post-whaling era, the origin of a small summer aggregation near Sakhalin Island, Russia (which we refer to as the Western North Pacific (WNP) stock) is unclear; this group may include descendants from the original western stock, founders from the eastern stock, or some combination of the two. To clarify the genetic affinities of WNP gray whales, we analyzed whole genome resequencing data for 71 individuals sampled from both geographic regions. Surprisingly, WNP whales are more genetically varied than ENP whales according to principal components and admixture analyses. We present evidence that this structure reflects mixed ancestry in the WNP, where some contemporary whales retain ancestry from the feared-extirpated western population, detectable as "ghost" introgression, while others are of eastern ancestry. Genomic signals based on both single nucleotide polymorphisms and on copy number variants indicate that despite mixed ancestry, the influx of recent eastern gene flow has largely homogenized genomic diversity across the Pacific. These findings highlight the ability of whole-genome data to help resolve questions of extirpation and to clarify complex gene flow dynamics in highly mobile species.

Alzheimer's disease (AD), a progressive neurodegenerative disease with a rising global prevalence, is characterized by amyloid-β (Aβ) aggregation, tau hyperphosphorylation, inflammation, oxidative damage, and neuronal apoptosis. Studies have increasingly recognized epigenetic modifications as key regulators in the development of AD. Epigenetic modifications, particularly histone acetylation, are increasingly recognized as critical regulators of cell survival and AD pathogenesis. Although artemisinin (ART) exhibits potent anti-oxidative, anti-inflammatory, and neuroprotective properties, its impact on histone acetylation in AD remains uncharacterized. This study investigated whether ART regulates histone acetylation to confer neuroprotection and rescue behavioral deficits in Alzheimer's disease models. Using SH-SY5Y cells, primary neurons, and 3xTg-AD mice, we found that ART restores histone acetylation homeostasis by enhancing histone H4 acetylation. Mechanistically, this effect is driven by the activation of the CaMK IV/PKA-CREB signaling cascade. Treatment with ART reduced ROS, improved mitochondrial function, decreased Aβ1-42 deposition, and suppressed neuronal apoptosis. However, these beneficial effects were abolished by PKA or CaMK IV inhibitors. Consequently, ART treatment significantly reduced reactive oxygen species (ROS) generation, restored mitochondrial function, decreased Aβ1-42 deposition, suppressed neuronal apoptosis, and alleviated AD-like neuropathology and cognitive deficits. Crucially, the neuroprotective and epigenetic benefits of ART were entirely abolished by pharmacological inhibitors of PKA or CaMK IV. This study is the first to demonstrate that artemisinin ameliorates AD pathology and behavioral impairments via the CaMK IV/PKA-CREB-Ace-H4 axis, establishing ART as a promising therapeutic candidate for epigenetic intervention in AD.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Platelets, traditionally recognized for hemostatic functions, have emerged as critical modulators of the HCC tumor microenvironment, yet their complex roles remain incompletely understood. This review synthesizes current mechanistic and clinical evidence on platelet functions in HCC pathophysiology and translational applications. Platelets exert dual, context-dependent effects in HCC. Their pro-tumorigenic mechanisms include circulating tumor cell shielding, epithelial-mesenchymal transition induction via TGF-β1/AMPK/mTOR signaling, and immunosuppression through GARP-TGF-β and GITRL pathways. Conversely, P2Y12-mediated CD40L secretion confers anti-tumor immunity in metabolic dysfunction-associated steatohepatitis-driven HCC (MASLD-HCC). Platelet functions vary by etiology, differs significantly between viral hepatitis and metabolic liver disease, and shift dynamically from early to advanced disease stages. Platelets remodel the immune microenvironment through interactions with T cells, NK cells, and macrophages, with platelet-derived extracellular vesicles and non-coding RNAs serving as key mediators. This offers potential translational applications including platelet-based biomarkers, etiology-stratified antiplatelet strategies, platelet membrane-coated nanoparticles for targeted drug delivery, and management of platelet-drug interactions in systemic therapy. Bridging mechanistic insights and clinical observations offers a potential framework for developing platelet-targeted precision approaches to improve HCC management.

Pathological deposition of endogenous material within tissues represents a central, unifying mechanism across a broad spectrum of prevalent human diseases. Atherosclerosis and Alzheimer's disease (AD) exemplify this paradigm: atherosclerosis is driven by subendothelial accumulation of apolipoprotein B-containing lipoproteins, cholesterol crystals, and hydroxyapatite, while AD is characterized by cerebral deposition of misfolded amyloid-β (Aβ) and/or hyperphosphorylated tau. Emerging evidence implicates substantial lipid dyshomeostasis in AD pathogenesis, including lipid-droplet-accumulating microglia and widespread lipidomic disruption, blurring the categorical boundary between "lipid" and "protein" deposition diseases. Apolipoprotein A-I (apoA-I) dysfunction bridges both domains: post-translational modifications and point mutations impair reverse cholesterol transport in atherosclerosis and simultaneously promote apoA-I amyloid fibril formation in systemic amyloidosis. Across atherosclerosis, AD, systemic amyloidoses, immune complex-mediated nephropathies, crystal arthropathies, and lysosomal storage disorders, shared pathophysiologic processes emerge: production-clearance imbalance, conformational transitions favoring aggregation or crystallization, microenvironmental modulation by extracellular matrix components, and chronic sterile inflammatory responses driven by NLRP3 inflammasome activation. In this review, we synthesize deposition biology using atherosclerosis and AD as primary paradigms, integrate mechanistic insights from related disorders, highlight convergent molecular pathways including NLRP3, proteostasis, and glymphatic clearance, and discuss diagnostic and therapeutic strategies. A conceptual framework unifying these conditions as variations on a common deposition theme is proposed to guide broadly applicable precision therapies.

This computational study investigates the molecular-level interaction between asphaltene (AO) nanoaggregates and the amphiphilic 1-(octylamino)propan-2-ol (OAP) inhibitor using density functional theory (DFT) calculations and complementary experimental analysis. Quantum theory of atoms in molecules (QTAIM) analysis indicates that OAP interacts with the AO surface through non-covalent interactions, with binding energies reaching - 24.67 kJ/mol and |VB|/GB ratios below unity. Electron localization function (ELF), localized orbital locator (LOL), non-covalent interaction (NCI), and highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO-LUMO) analyses suggest charge redistribution and electronic complementarity within the OAP-AO complex, supporting the proposed steric shielding mechanism. Complementary dynamic light scattering (DLS) measurements showed a reduction in the median aggregate size from 42.4 to 17.7 nm following OAP addition, which may indicate improved aggregate dispersion and enhanced colloidal stability. Collectively, the computational and experimental findings provide molecular-level insight into the proposed stabilization mechanism of the OAP-AO system and contribute to a better understanding of asphaltene inhibitor-aggregate interactions.

Interactions between food processing-derived components and food proteins can markedly alter protein conformation and functional properties. Among them, cooking oil fume particles (COFPs) are widespread contaminants from high-temperature Chinese cooking. This study first compared the effects of COFPs from four common edible oils (rapeseed, RCOFPs; soybean, SCOFPs; corn, CCOFPs; and lard, LCOFPs) on the OVA structure and function. Physicochemical assays showed that all COFPs triggered OVA aggregation (particle size increased from 0.48 to 896.86 nm) and reduced zeta potential, driving an ordered secondary structure remodeling with distinct component-specific patterns. RCOFPs enriched in polycyclic aromatic hydrocarbons (especially fluoranthene, stably binding OVA at -7.9 kcal mol[-1] through hydrophobic bonds) may be related to β-sheet enrichment, which directly promoted allergenic epitope exposure and resulted in enhanced IgE/IgG binding and KU812 cell degranulation. High-peroxide LCOFPs promoted disulfide bond formation and α-helix elevation, inducing compact conformational remodeling that enhanced OVA's gastrointestinal digestion resistance. Pearson analysis revealed a potential structure-function relationship. Soybean oil and corn oil exhibited weaker effects on the nutritional functionality of OVA than the other tested oils under the present experimental conditions. These findings clarify the regulatory effects of thermal processing contaminants on the health-related properties of food proteins, providing scientific guidance for the selection of edible oil in Chinese cooking and the nutritional and safety control of thermally processed egg products.

Transient receptor potential ankyrin 1 (TRPA1) is an evolutionarily conserved non-selective cation channel protein that converts diverse stimuli into intracellular Ca[2+] signals. Aquatic organisms provide valuable comparative systems for examining how environmental complexity shapes TRPA1 structure and function. In water, TRPA1 channels may be exposed to combined pressures from thermal stratification, hydrodynamic disturbance, chemical diffusion, salinity fluctuation, and redox changes. Although research on aquatic TRPA1 has expanded in recent years, most studies have focused on individual species, isolated stimuli, or behavioral phenotypes. A structure-function-oriented synthesis linking channel architecture, stimulus-dependent gating, Ca[2+] signaling, and physiological adaptation remains lacking. This review summarizes current knowledge of aquatic TRPA1 channels from a structure-function perspective. These channels generally retain a conserved architecture, including N-terminal ankyrin repeat domains, six transmembrane segments, and a central ion-conducting pore, while exhibiting lineage-specific variation in ankyrin repeat number, redox-sensitive cysteine residues, and transmembrane or regulatory amino acids. Such structural features may fine-tune conformational stability, ligand recognition, thermal responsiveness, redox sensitivity, and Ca[2+] signal output across aquatic taxa. Functionally, TRPA1 has been implicated in sensing or regulating responses to temperature, light/radiation, salinity, reactive chemicals, and mechanical cues. Emerging evidence further points to cross-modal integration of temperature-chemical, light-chemical, and mechanical-redox signals. Through Ca[2+]-dependent signaling pathways, TRPA1-mediated activation can be linked to stress defense, feeding metabolism, reproduction, neurogenesis, immunity, aggregation behavior, and host-symbiont interactions. Overall, aquatic organisms provide comparative models for understanding how TRPA1 channels link local structural plasticity to multimodal environmental sensing and adaptive physiological regulation.

In this work, red-fluorescent silver nanoclusters (MMTA@Ag NCs) with aggregation-induced emission (AIE) properties were synthesized via a facile one-pot strategy at room temperature using 2-mercapto-4-methyl-5-thiazoleacetic acid (MMTA) as the capping ligand. The as-prepared Ag NCs initially exhibited weak fluorescence in aqueous solution with a quantum yield of only 0.0037. Upon the introduction of Mn[2+], the metal ions acted as electrostatic bridges by coordinating with the carboxylate groups (-COO[-]) on the NCs surface, triggering significant aggregation of the nanoclusters. This aggregation effectively restricted intramolecular motion, leading to a remarkable "turn-on" fluorescence enhancement with a 100-fold increase in quantum yield to 0.38. Based on this AIE mechanism, a novel fluorescent sensing platform for Mn[2+] detection was established. The method exhibited a satisfactory linear response over the Mn[2+] concentration range of 0.01-0.50 µmol L[-1] with a low detection limit of 9.79 nmol L[-1] and excellent selectivity over other interfering ions. The proposed method was successfully applied to the determination of Mn[2+] in milk samples, with satisfactory recoveries ranging from 99.0% to 106.2% and RSD below 2.7%. Furthermore, a highly luminescent PVA composite film was fabricated using the MMTA@Ag NCs-Mn[2+] system, demonstrating promising potential in anti-counterfeiting applications.

BackgroundThis study aimed to systematically review randomized controlled trials (RCTs) comparing oral anticoagulant (OAC) monotherapy with combination therapy of OAC plus single antiplatelet therapy (SAPT) in patients with chronic coronary syndrome (CCS) and an indication for long-term anticoagulation.MethodsA systematic screening of the PubMed, EMBASE and Cochrane Central databases was conducted until 12 Mar 2026 to identify RCTs comparing OAC monotherapy with OAC plus SAPT in CCS patients. The primary endpoints were all-cause mortality and net adverse clinical events (NACE). Secondary endpoints included major bleeding, cardiovascular death, myocardial infarction, ischemic stroke and stroke. End point data were pooled using random-effect models, to generate hazard ratios (HR) and odds ratios (OR) and corresponding 95% confidence intervals (CI).ResultsSix RCTs involving 5048 patients were included. Pooled analysis showed that OAC monotherapy significantly reduced the risk of NACE compared to combination therapy (HR, 0.66; 95% CI, 0.44-0.77). There was no significant difference in all-cause mortality overall (HR, 0.75; 95% CI, 0.51-1.10). OAC monotherapy substantially decreased major bleeding (HR, 0.47; 95% CI, 0.32-0.70) and cardiovascular death (HR, 0.69; 95% CI 0.50-0.95) and there was no statistically significant difference in other secondary outcomes.ConclusionsCurrent evidence suggests that OAC monotherapy is a safer alternative to combination therapy in anticoagulated patients with CCS, without increasing ischemic risk.

Gas-phase aggregation of CO2 with organic compounds provides molecular-level benchmarks for understanding how weak interactions guide early cluster growth─a process relevant to CO2 recognition, uptake, and organization in chemically diverse environments. Here, clusters of maleic anhydride with one to three CO2 molecules were characterized by Fourier transform microwave spectroscopy in combination with quantum-chemical calculations. One isomer was identified in the pulsed jet for each cluster size. The dimer adopts a nearly coplanar structure in which CO2 binds at a carbonyl edge through a dominant C···O tetrel bond assisted by a weak cooperative C-H···O hydrogen bond. Growth to n = 2 and 3 is accompanied by pronounced structural reorganization rather than simple retention of the dimer geometry, with the initially bound CO2 substantially repositioned as distinct binding regions are sequentially occupied. These findings show that a compact, electronically differentiated host can redirect stepwise CO2 growth away from simple site-by-site addition, providing a molecular-level basis for understanding the early stages of CO2 recognition and uptake in organic host environments.

High-performance blue quantum-dot light-emitting diodes (QLEDs) typically employ poly(9,9-dioctylfluorene-co-N-(4-butylphenyl)diphenylamine) (TFB) as the hole transport layer (HTL). However, the insufficient energy barrier between the LUMO of TFB and the conduction band of blue QDs (BQDs) induces severe electron leakage, resulting in parasitic interfacial emission and compromised device stability. Herein, we investigate the structural evolution and optoelectronic degradation of TFB films during QLED aging via a charge functional layer peeling technique. We reveal that oxidation reactions occur both at the TFB/BQDs interface and within the bulk TFB film under operational stress. Driven by leaked electrons, the main and side chains of TFB molecules undergo scission and oxidation, generating abundant carrier traps associated with oxidation products (C2H3O+, C2H3O2+) and molecular fragments (C3H5+, C4H7+, C5H9+). Furthermore, this structural degradation downshifts the conduction band level of the TFB layer by 0.21 eV, thereby exacerbating electron leakage. Concurrently, the diminished hole mobility disrupts the carrier balance and increases exciton density in the emissive layer. This work elucidates the intrinsic HTL degradation mechanism in state-of-the-art QLEDs, providing critical insights for designing highly stable blue QLED devices.

Understanding and controlling the interplay between crystallinity and exciton dynamics is critical for developing more efficient organic thin films for semiconducting devices. In this work, in situ linear absorption and single-shot transient absorption measurements are used to characterize the molecular aggregation of copper phthalocyanine (CuPc) during film deposition, revealing an intermediate stage during deposition when the molecules have formed H-aggregates but have yet to agglomerate into a herringbone structure. Experiments with supersaturated solutions of CuPc showed that the steps of aggregation can be separated, with H-aggregates first forming in solution followed by columns of H-aggregates, of unknown length, coming together to form nanoribbons. Films cast from solutions of supersaturated CuPc have a more crystalline structure and fits to transient absorption spectra showed that exciton-exciton annihilation becomes more rapid compared to regular films. In addition to presenting a method to control exciton diffusion lengths in films that tend to adopt a herringbone packing structure, this study also provides a framework for how in situ spectroscopies can be used to design new aggregate structures and control exciton dynamics.