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This work focuses on how the structural regulation of nonfullerene acceptors (NFAs) improves the power conversion efficiency (PCE) of organic solar cells through terminal substitution and central core extension. Three series of NFAs (DONAD-X, DPT-X, and DOYAD-NO2) are designed by introducing different strong electron-withdrawing terminal substituents (X) and extended conjugated central cores (Y). High-precision density functional theory (DFT) and time-dependent DFT calculations are employed to comprehensively investigate their ground-state and excited-state properties. The calculation results reveal that strong electron-withdrawing terminal substituents are beneficial for NFA to effectively reduce the molecular energy gap, broaden the absorption spectrum, and increase the electron mobility. Symmetric substitution is more effective than asymmetric substitution in achieving longer maximum absorption wavelength and smaller excitation energy. The introduction of symmetric terminal substitution and synergistic effect of both -CN and -NO2 groups (abbr -CNO2) enables NFA to achieve optimal performance. Furthermore, the extended conjugated central cores effectively enhance the chemical reactivity and intramolecular charge transfer (ICT) of the NFAs. Based on the selection of the optimal terminal substituent and central core, we construct the most promising acceptor DOIAD-CNO2 and find that the PM6/DOIAD-CNO2 interface possesses the largest short-circuit current density and PCE (16.39%). The CT mechanisms of the designed PM6/NFA interfaces involve the coexistence of hot exciton excitation, intermolecular electric field, and direct excitation, which can promote more exciton separation. PM6/DOIAD-CNO2 has the most CT and FE/CT states with larger oscillator strengths, thereby obtaining the largest PCE. This work can inspire the experimental synthesis and application of these acceptor candidates and provide guidance for further design and development of more efficient NFAs.

We aimed to evaluate the utility of 5-T Gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) by intraindividual comparison with 3-T MRI, with a focus on the image quality and diagnosis of hepatocellular carcinoma (HCC). We prospectively enrolled 41 patients with suspected HCC who underwent dynamic Gd-EOB-DTPA-enhanced MRI using both 5-T and 3-T scanners. Artificial intelligence-assisted compressed sensing (ACS) and parallel imaging (PI) were both used for hepatobiliary phase (HBP) imaging at 5-T. Two radiologists performed qualitative and quantitative assessments of image quality and evaluations of imaging features. Wilcoxon signed-rank, paired &#x3c7;2, and Cochran Q tests as well as intraclass correlation coefficients and the Cohen &#x3ba; value were used. All subjective image quality scores ranged from good to excellent. The subjective scores of contrast-enhanced phases for 5-T images were higher than those for 3-T images (all p&#x2009;<&#x2009;0.05), except for image artifacts. For diffusion-weighted imaging (DWI), the subjective scores of the clarity of the lesion margins on 5-T images were higher than those on 3-T images (p&#x2009;=&#x2009;0.021). Quantitative measures were also greater for 5-T images (all p&#x2009;<&#x2009;0.05). For DWI, the contrast ratio (CR) at 5-T was greater (p&#x2009;<&#x2009;0.05). Subjective and quantitative assessments of HBP imaging were higher with ACS (all p&#x2009;<&#x2009;0.05). The detection rate of enhancing capsule was greater for 5-T images (p&#x2009;=&#x2009;0.016), as was the rate of peritumoral hypointensity on the HBP images at 5-T using ACS (p&#x2009;=&#x2009;0.015). Compared with 3-T MRI, liver dynamic Gd-EOB-DTPA-enhanced 5-T MRI demonstrated superior image quality for contrast-enhanced phases and greater sensitivity in detecting enhancing capsule in HCC. The integration of 5-T MRI and ACS technology has the potential to further improve image quality and the assessment of imaging features. Gd-EOB-DTPA-enhanced 5-T MRI provides promising potential for accurate HCC evaluation.

Neuropsychiatric (NP) manifestations are common, heterogeneous and severe in systemic lupus erythematosus (SLE) patients, with attribution to SLE remaining diagnostically challenging. Traditional classification focuses on clinical syndromes, overlooking neuropsychiatric systemic lupus erythematosus (NPSLE) immunological heterogeneity. To address the heterogeneity of NPSLE, this study aimed to delineate distinct disease subgroups by clustering patients based on their antibody profiles. These subgroups were then evaluated for diferences in clinical presentation and prognosis, to better characterize disease subsets and support individualized approaches to diagnosis and management. This retrospective single-center study included hospitalized SLE patients with NP manifestations, collecting demographic, clinical and laboratory data. Patients were classified as NPSLE or non-NPSLE by clinical judgment after excluding alternative causes. Hierarchical cluster analysis explored autoantibody-clinical feature associations. Among the 167 patients analyzed, 152 had NP manifestations attributed to SLE. Central nervous system (CNS) involvement was predominant (89.1%), with seizures, cerebrovascular disease, acute confusional state (ACS), and demyelinating syndrome being most prevalent manifestations. Hierarchical clustering of 152 NPSLE patients identified two subgroups: Cluster 1 (23.7%) demonstrated cerebrovascular injury as the predominant manifestation, with higher positivity rates of antiphospholipid antibodies (APLs) (P < 0.01) and a higher incidence of cerebrovascular disease (P < 0.01). Cluster 2 (76.3%) showed immune-mediated inflammatory profile, with higher positivity of anti-SSA (P < 0.01), antidsDNA (P < 0.05), and anti-RiboP antibodies (P < 0.05). Neurological involvement predominantly manifesting as ACS (P < 0.05), accompanied by a higher frequency of fever and joint involvement. In this study, NPSLE exhibited distinct serological profiles and segregated into two immunologically defined clusters, reflecting its clinical and biological heterogeneity, and suggesting that immunological profiling may enhance precise classification and personalized management of affected patients.

The rational design of trifunctional electrocatalysts capable of driving the oxygen evolution reaction (OER), oxygen reduction reaction (ORR), and hydrogen evolution reaction (HER) remains a central challenge in renewable energy conversion. In particular, it remains insufficiently understood whether these reactions proceed on a universal active site or arise from reaction-dependent site specialization and multisite cooperation in single-atom catalysts. Herein, we perform a systematic density functional theory (DFT) screening of transition-metal (TM) single atoms anchored at oxygen vacancy sites of Nb2CO2 MXenes to identify stable and experimentally viable trifunctional SACs. Among the candidates, Pt-Nb2CO2 exhibits favorable conductivity, thermodynamic stability, and competitive trifunctional electrocatalytic activity, with overpotentials of 0.42 V for OER, 0.60 V for ORR, and -0.07 V for HER, comparable to benchmark catalysts such as Pt(111) and IrO2(110). Detailed electronic structure analyses reveal that the trifunctional activity originates from multisite cooperative catalysis. The d orbitals of the TM atoms dominate the activity of oxygen-related reactions (OER/ORR), where the d-band center, modulated by bandwidth effects, correlates well with the activity trends. In contrast, the HER activity is governed by TM-induced charge transfer and site-specific hydrogen binding characteristics. This work clarifies the electronic origin of multisite cooperative trifunctional electrocatalysis in TM-MXene SACs and provides a rational theoretical framework for the design of experimentally accessible multifunctional electrocatalysts.

Electropolymerization has emerged as a versatile electrochemical strategy for creating functional films of conjugated polymers, offering molecular-level tunability and spatial control. Beyond its simplicity and reagent-free nature, this approach provides a unique window into how interfacial environments, charge-transfer kinetics, and molecular coupling collectively dictate polymer growth and functionality. Because the resulting material properties are rooted in the delicate interplay between interfacial structure and reaction mechanism, unraveling these correlations remains central to both mechanistic understanding and rational material design. Recent efforts, including copolymerization, templated electropolymerization, and layer-by-layer strategies, have expanded the accessible structural and functional landscape, yet precise control of molecular architecture at electrochemical interfaces continues to pose significant challenges. This Outlook highlights emerging mechanistic insights and underscores the transformative role of advanced in situ and operando characterization techniques in bridging nanoscale structural evolution with macroscopic electrochemical behavior, ultimately pointing toward a mechanism-guided framework for designing next-generation conjugated polymers.

Pathological aggregation of &#x3b1;-synuclein is a hallmark of synucleinopathies such as Parkinson's disease, where fibrillar &#x3b1;-synuclein aggregates drive neurodegeneration. Here, we aimed to identify small molecules capable of disassembling fibrillar &#x3b1;-synuclein aggregates by screening a natural product library using a plasmonic nanoparticle amyloid corona platform. Candidates were further ranked based on key physicochemical properties (molecular weight, solubility, and lipophilicity) associated with cell permeability and potential central nervous system accessibility. Through this analysis, angelic acid emerged as the top candidate. Physicochemical characterization, including circular dichroism, Fourier-transform infrared spectroscopy, transmission electron microscopy, and atomic force microscopy, demonstrated that angelic acid disrupts &#x3b2;-sheet-rich conformations and fragments &#x3b1;-synuclein fibrils. Molecular docking analysis suggested potential interactions of angelic acid with &#x3b2;-sheet interface regions across multiple &#x3b1;-synuclein fibril polymorphs. In a bimolecular fluorescence complementation cell model, angelic acid reduced intracellular &#x3b1;-synuclein accumulation by up to 91.4% at 100 &#x3bc;M. In addition, angelic acid alleviated &#x3b1;-synuclein fibril-induced cytotoxicity by 34.1%, demonstrating both reduced cellular &#x3b1;-synuclein levels and attenuation of &#x3b1;-synuclein fibril-induced cytotoxicity. Collectively, these findings suggest that angelic acid is a pathological &#x3b1;-synuclein-targeting lead compound for synucleinopathies, highlighting the need for further in vivo evaluation in synucleinopathy models.

Stress granules (SGs) are cytoplasmic, membraneless assemblies of proteins and RNAs that transiently form in response to cellular stress. Dysregulation of SGs has been associated with cancer, neurodegeneration, and viral infection. GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a central SG component that regulates granule assembly and dynamics through protein-RNA and protein-protein interactions (PPIs). During viral infection, SGs can be hijacked to enhance viral replication and suppress host defense. In this study, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (N) binds G3BP1 and localizes to G3BP1-positive SGs in infected cells. We hypothesize that small-molecule ligands targeting G3BP1 can disrupt the G3BP1-N interaction and reduce viral replication. To test this, we developed a robust, miniaturized, 384-well time-resolved fluorescence resonance energy transfer (TR-FRET) assay for high-throughput screening (HTS). Screening a library of 2560 FDA-approved drugs yielded 17 hits. Subsequent counterscreening, validation, and biophysical binding studies identified 7 PPI inhibitors with IC50 values ranging from 0.8 to 31 &#x3bc;M. In cell-based assays, two compounds&#x2500;dexlansoprazole and citalopram&#x2500;disrupted the G3BP1-N interaction with minimal cytotoxicity. Both compounds showed antiviral activity in human lung epithelial cells infected with either the WA strain or an Omicron (BA.1) strain of SARS-CoV-2. This work establishes a strategy to modulate SGs by targeting a host-virus PPI, highlighting G3BP1 as a potential therapeutic node for antiviral intervention.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation, driven by immune dysregulation. One of the key contributors to this persistent inflammation is the dysregulation of dendritic cells (DCs) in the gut and mesenteric lymph nodes (MLNs), particularly through CD40 signaling, which plays a central role in modulating immune responses. Targeting CD40 in DCs therefore represents a promising approach for restoring immune balance and improving IBD. In this study, we developed maleimide (Mal)-modified PEG-PLGA nanoparticles for the targeted delivery of siCD40 to DCs in the gut and MLNs. In a TNBS-induced colitis mouse model, Mal-modified siCD40 nanoparticles significantly alleviated intestinal inflammation, improved colonic histopathology, and induced a marked increase in regulatory T cells (Tregs) within the gut and MLNs, promoting immune tolerance while preserving gut microbiota composition. Furthermore, Mal-modified nanoparticles effectively improved gut inflammation and maintained immune tolerance even at low doses. Our findings suggest that Mal-modified PEG-PLGA nanoparticles offer a promising strategy for targeted IBD treatment by modulating local immune responses, restoring immune tolerance, and maintaining gut homeostasis. Moreover, this nanoparticle-based localized and precise immune modulation approach may provide valuable insights into the treatment of organ-specific immune-mediated diseases.

Inflammation and oxidative stress are central mediators of acute and chronic diseases. Here, we present a chitosan-stabilized silver-nimesulide coordination complex engineered to enhance anti-inflammatory and redox-modulating performance while enabling controlled drug release. Spectroscopic and crystallographic analyses confirmed the formation of an Ag-NMS coordination core embedded within a polymeric chitosan matrix. The biocomposite significantly reduced carrageenan-induced edema, MPO activity, and lipid peroxidation, while modulating thiol-dependent redox responses. These findings demonstrate that coordination-driven polymeric stabilization improves the therapeutic profile of nimesulide and supports further preclinical investigation of this multifunctional biocomposite.

Ceramide is a central bioactive lipid that acts as both a membrane structural component and a crucial signaling molecule in the cells. In order to maintain cellular homeostasis, ceramide metabolism is tightly regulated by enzymes in the endolysosomal system such as acid ceramidase (AC) and acid sphingomyelinase (ASM). We investigate the biochemical consequence of ceramide accumulation within the endolysosomes of living animal cells by optical nanoprobing, using surface-enhanced Raman scattering (SERS) with gold nanoparticles. The ceramide level in 3T3 fibroblast cells was systematically increased by interfering with two key enzymatic pathways in sphingolipid metabolism as well as by adding exogenous ceramide. The modulation of enzyme activity occurred by the inhibition of AC using the inhibitor N-[(2S,3R)-1,3-dihydroxyoctadecan-2-yl]2-chloroacetamide (SACLAC) in different incubation schemes and supplementation of the cells with additional ASM, respectively, both were added through the culture medium. The analysis of SERS data from the endolysosomal compartment reveals changes in the structure and interaction of proteins alongside variations in membrane composition and organization that correspond to ceramide stress. Combined cryo soft-X-ray nanotomography data of the intact cells show that the biomolecular alterations transform the cellular ultrastructure to varying degrees depending on the specific route and extent of ceramide increase. The ultrastructural changes include severe membrane deformation and changed vesicular organization as a consequence of a high ceramide content. The results demonstrate the label-free optical monitoring of metabolic processes at the subcellular level, before their complex biochemical background, and refine the description of molecular and nanostructure changes associated with distorted sphingolipid metabolism.

Balamuthia mandrillaris is a free-living amoeba that causes granulomatous amoebic encephalitis, a rare but devastating central nervous system infection with mortality exceeding 95%. Treatment relies on empirical, multidrug regimens lasting several months, yet prognostic indicators and optimal dosing strategies remain undefined. Advances in computational biology now permit the creation of digital twins, data-driven and patient-specific virtual replicas that integrate clinical, imaging, molecular, and pharmacological data to simulate disease dynamics and therapeutic response. By incorporating molecular mechanisms of Balamuthia pathogenesis and host susceptibility into such a model, it becomes possible to forecast treatment trajectories, personalize drug dosing, and predict toxicity in real time. This paper outlines the molecular and immunological underpinnings of Balamuthia infection and proposes a digital twin framework that bridges mechanistic biology with predictive analytics to improve management and survival in this neglected infection.

Fibromyalgia (FM) is a chronic pain syndrome marked by widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive dysfunction. Despite extensive research, its pathophysiology remains unclear. Emerging evidence implicates the gut microbiome (GMB) in FM through mechanisms involving pain modulation, immune dysregulation, and neuroinflammation. This review explores the role of gut dysbiosis in FM pathogenesis, focusing on microbial alterations, immune interactions, intestinal permeability, and neurochemical pathways. A systematic search of PubMed, Scopus, and Web of Science was conducted to identify studies published in the last two decades examining the relationship between GMB and FM. Inclusion criteria encompassed original research, systematic reviews, and meta-analyses addressing microbial dysbiosis, immune modulation, and neurochemical alterations in FM. Studies focused solely on treatment interventions were excluded. A narrative synthesis approach was used to integrate findings and highlight mechanistic insights. FM patients exhibit significant gut microbial dysbiosis, including reduced butyrate-producing bacteria and increased pro-inflammatory species. These alterations are associated with compromised intestinal barrier integrity, systemic immune activation, and elevated pro-inflammatory cytokines. Neurochemical disruptions include serotonin deficiency, gamma-aminobutyric acid/glutamate imbalance, and reduced short-chain fatty acids, contributing to central sensitization and neuroinflammation. Dysregulation of the gut-brain axis and microbial metabolite pathways further exacerbate FM symptoms. GMB dysbiosis plays a pivotal role in FM pathogenesis through immune activation, intestinal permeability changes, and neurochemical modulation. Understanding these mechanisms may inform future research into microbiome-based biomarkers and therapeutic strategies. While treatment implications are beyond the scope of this review, the findings underscore the potential of targeting microbial pathways in FM management.

Ensuring signal fidelity and output stability against electrical noise is a central challenge for optoelectronic sensing-computing systems. However, conventional optoelectronic devices often suffer from output instability due to input voltage fluctuations. This limitation hinders the realization of multifunctional logic operations with high interference immunity in a single device. Here, we propose a photon-assisted Fowler-Nordheim tunneling regulator based on a SnS2/WSe2 van der Waals heterostructure. Through a gate-activated, light-programming strategy, the device achieves a voltage-immune constant current output. Leveraging these intrinsic physical properties, reconfigurable logic units were constructed. The NOT logic gate achieves a switching ratio of up to 104, while the robust NAND logic gate exhibits remarkable noise immunity (coefficient of variation, CV &#x223c; 1%), effectively filtering noise jitter from input signals to ensure precise logic output. This work applies the photon-assisted tunneling effect to both analog signal conditioning and digital logic operations, highlighting the immense potential of light as a programming tool for quantum transport processes and providing a distinct device prototype for the development of interference-resistant and multimodal integrated on-chip optoelectronic systems.

Abiotic stresses caused by climate change pose a serious threat to global crop productivity, making the early detection of plant stress responses crucial. Hydrogen sulfide (H2S) and hydrogen peroxide (H2O2), as key signaling molecules, their dynamic synergistic effects are central to understanding the mechanisms of plant stress adaptation. However, real-time tracking of the dynamic changes of these molecules remains challenging. This study developed a wearable plasmonic nanoarray sensor integrated with metal-organic frameworks (MOFs), which cleverly combines the high sensitivity of surface-enhanced Raman scattering (SERS) with the gas enrichment capacity of the MOF, incorporates 2D plasmonic membrane assembly technology and 4-mercaptophenylboronic acid (4-MPBA) conjugation strategy, and successfully achieves real-time and synchronous detection of H2S and H2O2 in plants. The 24 h dynamic monitoring results showed that under different stress conditions, H2S and H2O2 in tomatoes and rice both had specific dynamic change rules, and there was a complex cross-regulation mechanism between them. By combining sensor data with partial least squares discriminant analysis (PLS-DA), the classification accuracy of stress types exceeds 95%. This non-destructive and highly sensitive detection system can provide real-time dynamic data of stress signals, bringing a breakthrough to the in-situ monitoring of plant physiological states.

Understanding lattice dynamics is crucial for optimizing the process of creating functional structures, such as laser writing of color-center defects. However, existing structural probes have difficulty measuring structural dynamics with submicrometer depth sensitivity. Here, a depth-resolved ultrafast X-ray nanodiffraction technique is developed to track the lattice dynamics of silicon carbide (SiC) in three dimensions. Upon laser excitation of an aluminum layer that acts as a heat and strain transducer, a specular Bragg peak of SiC shows an overall increase in the X-ray diffraction intensity rather than a peak shift. The relaxation dynamics of the increased intensity are significantly different when probed on and off the Bragg peak. The fast subnanosecond relaxation probed at the maximum of the Bragg peak is a result of the propagation of a coherent strain wave along the depth direction, while a slow relaxation probed at the wings of the Bragg peak reflects a localized incoherent lattice heating. To further visualize these processes, spatiotemporal maps were obtained by scanning the relative position and delay between the laser pump and X-ray probe beams, which capture the propagation of the strain wave, as well as a stationary structural distortion close to the aluminum/SiC interface. These depth-resolved structural measurements disentangle energy dissipation mechanisms in laser-excited SiC, and they open opportunities for finer control of, for example, the formation of optically addressable defect complexes central to quantum information applications.

2'-5'-Oligoadenylate synthetases (OAS) are crucial innate immune sensors that activate antiviral responses upon detecting viral double-stranded RNA. Understanding the molecular mechanism of OAS is vital for advancing immunomodulatory therapies. This study provides a detailed enzymatic mechanism of the OAS, integrating structural, kinetic, and quantum chemical analyses. Crystallographic data of the OAS1 postreactive complexes shed light on the geometry of OAS1 following product formation and dissociation, the sequential order of product release, and the pivotal role of divalent metal ions in catalysis. Our data reveal the unanticipated involvement of a third metal ion, which may play a transient supporting role in the catalytic cycle. Moreover, they highlight the central role of quantum mechanisms in the OAS function. Strikingly, substituting catalytic Mg2+ with Mn2+ ions increases the substrate binding rate 9-fold and activates OAS for catalysis. The results of this study are pertinent to the OAS/cGAS family of innate immune sensors and offer insights that can be applied to a broader class of nucleotidyltransferases, which play key roles in various biological processes.

The application of mechanical force to drive selective chemical transformations represents a central goal in polymer mechanochemistry, with mechanocatalysis emerging as a key strategy for achieving reaction amplification. Existing systems, however, are confined to ionic or coordination-based pathways, leaving the vast landscape of radical-mediated catalysis largely unexplored. Although sophisticated mechanophores can generate specific radical species, these intermediates have been limited to stoichiometric roles&#x2500;as initiators, reporters, or reactants&#x2500;rather than as participants in catalytic cycles. Herein, we introduce the concept of mechanogated radical organocatalysis to bridge this fundamental gap. We report the rational design of an N-benzhydryloxyphthalimide (PINO-DPM) mechanophore that, under ultrasonic activation, undergoes selective C-O bond cleavage to directly release the stable, catalytically competent phthalimide N-oxyl (PINO) radical. This species functions as a hydrogen-atom transfer catalyst for the aerobic oxidation of aldehydes with a turnover number exceeding 600&#x2500;a direct quantitative measure of how a single bond-breaking event is amplified into sustained chemical output. This work thereby bridges the long-standing divide between force-activated radical generation and productive catalysis, opening new avenues for the development of force-responsive polymer materials with versatile functions.

Dental caries, the most common oral disease with a worldwide burden, causes structural damage to enamel and dentine. Considering the limitations of conventional restorative approaches and the dynamic nature of caries, biomimetic remineralization strategies offer a promising alternative for restoring tooth structure. Central to many of these strategies is the use of polymers to emulate the role of macromolecular templates in natural mineralization processes. This review summarizes the polymers applied for biomimetic mineralization of enamel and dentine according to their primary functions. Furthermore, perspectives on the trends and challenges for future research on polymeric biomaterials for enamel and dentine repair are also presented.

Treating central nervous system (CNS) disorders remains a major clinical challenge. The blood-brain barrier (BBB), systemic toxicity, and first-pass metabolism are key obstacles. These factors limit the effective drug delivery to the brain. Intranasal administration has emerged as a noninvasive strategy to bypass the BBB. This approach enables direct drug delivery to the brain through the olfactory and trigeminal nerve pathways, commonly referred to as nose-to-brain (N2B) delivery. In this context, chitosan (CS), a biocompatible and mucoadhesive polysaccharide with permeation-enhancing properties, has gained significant interest as a functional material for nanoparticle (NP) engineering. CS-based or CS-coated NP can prolong the residence time on the nasal mucosa and facilitate drug transport to the CNS. This review provides a comprehensive overview of recent advances in CS-based NP for N2B drug delivery across a range of CNS disorders, including neurodegenerative, neuropsychiatric, neoplastic, and infectious conditions. Particular attention is given to formulation strategies, mechanistic insights, and preclinical outcomes. Recent patent applications are surveyed to underscore the translational potential and commercial interest in this technology. Collectively, CS-based NPs effectively address major therapeutic barriers, establishing a transformative and innovative platform in CNS drug delivery.