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Realizing the practical application of spinel LiNi0.5Mn1.5O4 (LNMO) cathodes requires electrolytes with fast-charging capability and wide-temperature adaptability, which conventional electrolytes lack due to insufficient high-voltage stability, sluggish ion transport, and unstable interphases. Herein, we propose a salt-in-salt mediated "strong-weak synergy" strategy for fluorinated weakly solvating electrolytes (WSEs), distinct from conventional ether-based or single-component WSEs. Harnessing the moderate Lewis acidity of Mg2+ from Mg(TFSI)2, we promote LiDFOB dissociation to enrich anion-rich contact ion pair/aggregate (CIP/AGG) solvation structures, while concurrently inducing a "drag" effect on Li+-coordinated solvents/anions to synergistically accelerate Li+ desolvation. Notably, Mg2+ from inorganic MgF2 dynamically captures interfacial anions, directing the formation of a thin, robust inorganic CEI. This dual-regulation mechanism simultaneously optimizes bulk electrolyte ion conduction and interfacial stability, overcoming the intrinsic limitations of poor oxidation resistance and sluggish kinetics in traditional WSEs. Consequently, LNMO||Li cells exhibit exceptional fast-charging capability and cycling stability across a wide temperature range (-30 to 70°C), with pouch cells retaining 88.9% capacity after 400 stable cycles. The developed electrolyte also exhibits non-flammability and broad compatibility for nickel-rich LiNi0.8Co0.1Mn0.1O2, LiNi0.92Co0.06Mn0.02O2 and olivine-type LiFePO4 cathodes. This work offers fundamental insights into solvation chemistry and interfacial engineering toward safe, high-performance lithium-ion batteries.

The present review article explores the emerging evidence on the use of autologous platelet concentrates (APCs) as sustained release vehicles for a variety of drugs, including antibiotics, antifungals, antidiabetic drugs, exosomes, and vitamins for localized delivery approaches. The incorporation of such bioactive agents into APCs could enhance their therapeutic efficacy, support antimicrobial effects, wound healing and regeneration, and potentially reduce the need for systemic therapy. Although platelet-rich plasma (PRP) has also been studied as a carrier of bioactive agents, the rapid degranulation of platelets and lack of a cohesive fibrin network in PRP lead to a short-lived burst-type release profile. On the other hand, platelet-rich fibrin (PRF) has a three-dimensional scaffold of fibrin in which the growth factors and drug agents are retained, characteristics which make PRF-based APCs advantageous over PRP in the field of drug-delivery systems. However, a major challenge remains to be the absence of standardized drug-loaded APCs preparation protocols, with variations in centrifugation parameters, tube composition, and biomolecules' loading techniques, thereby influencing the APCs' structural integrity and release kinetics. The present review further highlights key findings on optimal loading strategies and the interactions between incorporated agents and the carrying APCs. It further highlights the level of current evidence for each of these drug-loaded APCs under investigation, their strength of recommendation, and possible knowledge gaps. Future work should focus on further developing and standardizing preparation protocols, advancing controlled release technologies, and validating efficacy through large scale clinical trials. Overall, bioactive drug-loaded APCs could represent a promising platform for targeted antimicrobial, antifungal, and regenerative therapies, bridging infection management with precision-guided tissue healing.

Ischemic stroke is a fatal cerebrovascular disease, and reperfusion, the primary approach for restoring blood supply, can lead to significant oxidative stress and subsequent damage to the cerebrovascular system. Developing strong antioxidant agents could be a solution, but it remains a Herculean challenge. Herein, inspired by the three-dimensional coordination structures and active center of natural Mn-superoxide dismutase, coupled with the synergistic monoatom/cluster sites found in antioxidases, we propose the de novo design of Mn-organic complex-supported Ru clusters (MnCP-Ru) to function as an artificial metalloenzyme for cascade elimination of reactive oxygen species (ROS), aimed at protecting against cerebral ischemic-reperfusion injury. Our studies show that Mn-organic ligands increase the electron density of Ru clusters, thereby improving their binding to oxygen species and resulting in effective, cascade-like antioxidase activities. Accordingly, the MnCP-Ru can reduce the number of apoptotic neurons by attenuating ROS-induced cell damage and exert powerful anti-inflammatory effects by inhibiting lipid peroxidation, microglial and astrocyte activation in brain tissues, thus leading to powerful protection and repair of cerebral ischemia-reperfusion injury. We believe the MnCP-Ru biocatalyst, with its synergistic sites and cascade ROS elimination, offers effective antioxidative performance, paving the way for developing materials to treat ischemic-reperfusion injury and other oxidative stress-related diseases.

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To assess current utilization of the Prosthodontic Diagnostic Index (PDI), identify perceived benefits and limitations, and evaluate support for future updates. A survey regarding the use of the PDI was made available through email invitations to 68 US dental school prosthodontic/restorative department chairs (PD), 48 graduate prosthodontic program directors (GP), and 1834 private practice prosthodontists (PP) from the American College of Prosthodontists (ACP) member database. The results of this initial survey were inconclusive due to low response rates. The survey was also administered during the 2024 ACP Annual Session with an improved response rate for educators. Descriptive statistics were used to analyze responses from predoctoral education programs and graduate prosthodontic programs. Responses were received from 43.8% (n = 21) graduate prosthodontic programs (GP) and 35.3% (n = 24) predoctoral programs (PD). The PDI was taught to graduate prosthodontic residents at 100% (n = 21) of the responding programs and at 58% (n = 14) of responding predoctoral programs. In contrast, the response rate for private practice prosthodontists, 2% (n = 43), was too low for statistical analysis. The PDI was used for new patient screening in 76.2% (n = 16) of GP and 41.7% (n = 10) of PD programs. The PDI was valued for enhancing diagnostic consistency (81.0%, n = 17 GP and 83.3%, n = 21 PD) and objective patient screening (90.5%, n = 19 GP and 87.5%, n = 21 PD). Common themes were observed in open-ended questions regarding the limitations of the PDI, including that the system was cumbersome, complicated, time-consuming to use, issues with calibration across all cohorts, and lacked recognition by general dentists and other dental specialists. The majority of respondents agreed that the PDI needs an update (76.2%, n = 16 GP and 66.7%, n = 16 PD), including the development of an ACP-endorsed classification system for implant-based treatment (81.0%, n = 17 GP and 91.7%, n = 22 PD). The PDI is viewed as a beneficial diagnostic and educational tool in academic settings. However, it is complex and has limited alignment with contemporary prosthodontic practice. A revision of the classification system could address current limitations and better support clinical decision-making.

Polysaccharides derived from Angelica dahurica exhibit potent wound healing activity, yet the pronounced structural heterogeneity of natural extracts has obscured the identity of the active motif and hindered clinical translation. Here we report a convergent, one-pot [22+22+22] glycosylation strategy based on glycosyl donor preactivation that enables the precise chemical synthesis of a 66-unit A. dahurica polysaccharide. This approach facilitates the efficient assembly of a comprehensive glycan library spanning tetrasaccharides to the full-length 66-mer polysaccharide, allowing for systematic biological evaluation. Functional screening identifies the reducing end hexasaccharide as the minimal active motif responsible for wound healing activity. Mechanistic analyses reveal that the synthetic hexa- and dodecasaccharides promote fibroblast and keratinocyte proliferation and migration, while concurrently reprogramming macrophage polarization. Crucially, gram-scale synthesis of both glycans enables definitive in vivo evaluation, demonstrating significantly accelerated wound closure through attenuation of excessive inflammation and promotion of organized collagen deposition. Collectively, these findings establish a general paradigm for deconvoluting heterogeneous natural polysaccharide extracts through de novo synthesis of structurally well-defined glycans as precision-engineered wound healing therapeutics.

This study aimed to provide a comprehensive comparison of inhibitory control performance among children with Attention-Deficit/Hyperactivity Disorder (ADHD), Specific Learning Disorder (SLD), and comorbid ADHD+SLD, relative to typically developing peers. It sought to clarify whether inhibitory control deficits are generalized across tasks or specific to distinct types of inhibition. A total of 120 children (30 per group; aged 9-11 years) participated. Three tasks assessed different facets of inhibitory control: the Stroop Color-Word Test (interference suppression), the Cued Go/No-Go Task (prepotent response inhibition), and the Stop-Signal Task (cancellation of ongoing responses). Analyses controlled for baseline processing speed. Findings revealed distinct inhibitory profiles. Children with ADHD showed broad deficits across all tasks, most pronounced in the Cued Go/No-Go Task, indicating a core weakness in prepotent response inhibition. The SLD group demonstrated slower reaction times, particularly in the Cued Go/No-Go Task in the initial analysis. Slower responses reflect both processing-speed deficits and potential differences in motor planning and execution. However, after statistically controlling for these general speed effects, the SLD group's profile revealed a specific and significant deficit only in interference suppression, with no core impairment in prepotent response inhibition or action cancellation. The comorbid ADHD+SLD group exhibited the most severe and pervasive deficits across all measures, exceeding single-diagnosis groups, suggesting a synergistic impairment. These results support the multidimensional nature of inhibitory control and highlight disorder-specific neurocognitive signatures. The findings underscore the need for differentiated assessment and intervention approaches targeting distinct inhibitory processes and processing-speed deficits, particularly in children with comorbid conditions.

The role of extracellular acidity in regulating parathyroid hormone (PTH) secretion in cultured mouse parathyroid glands (PTGs) has not studied to date, largely due to the technical difficulty of isolating mouse PTGs. We hypothesized that acidic extracellular pH directly stimulates PTH secretion through activation of a proton-sensing receptor, specifically ovarian cancer G protein-coupled receptor 1 (OGR1, also known as GPR68). To test this, we developed a method to reliably identify and isolate PTGs from male mice by administering 5-aminolevulinic acid (5-ALA), which induced selective fluorescence in these glands. Using this model, we demonstrate that acidic extracellular pH significantly stimulates PTH secretion in cultured mouse PTGs. Mechanistically, we identify OGR1 as the primary proton sensor mediating this response, as PTGs from OGR1 knockout mice failed to increase PTH secretion under acidic conditions, with no evidence of compensatory upregulation of other proton-sensing receptors. In addition, we found that low extracellular Ca2+ not only stimulates PTH secretion but also promotes extracellular acidification. Notably, low Ca2+ and acidic pH act synergistically to enhance PTH secretion in wild-type PTGs, an effect markedly attenuated in OGR1-deficient glands. Together, these findings establish a direct, OGR1-dependent mechanism by which extracellular acidity regulates PTH secretion and reveal an interaction between calcium and pH signaling in this process. This work provides a robust ex vivo model for studying PTG physiology and offers new insight into how metabolic acidosis may contribute to secondary hyperparathyroidism in chronic kidney disease, highlighting OGR1 signaling as a potential therapeutic target.

Late diagnosis of colorectal cancer (CRC) remains a public health challenge due to limitations in screening programs. This study evaluated the fecal immunochemical test (FIT) as an alternative screening method for CRC detection. Colonoscopy and immunochemical analysis were used as standard diagnostics. A population-based survey in Kazakhstan assessed disease prevalence and screening outcomes. Diagnostic accuracy and prognostic value of haemoccult testing were analyzed, comparing quantitative and qualitative results. Among 6,000 participants, 9.76% (n&#x2009;=&#x2009;586) had positive FIT results. Elevated fecal hemoglobin concentrations (&#x2265;100&#x2009;&#xb5;g Hb/g stool) were found in 3.6% (n&#x2009;=&#x2009;217), while 96.4% (n&#x2009;=&#x2009;5786) had lower values. Of 150 clinically significant positive cases, 55 were confirmed, including 5 CRC cases and precancerous conditions. FIT facilitated large-scale screening. The Positive Predictive Value (PPV) for qualitative FIT was 10.4%, and for quantitative FIT (&#x2265;100&#x2009;&#xb5;g Hb/g), it was 15.7%. The Negative Predictive Value (NPV) for qualitative FIT was 100%, and for quantitative FIT, 99.5%. These results support FIT as a reliable, noninvasive tool for early CRC detection, particularly with proper triage. FIT demonstrates practical value as an efficient screening tool for early CRC detection, with a weak but significant correlation to histological findings (p&#x2009;<&#x2009;0.01).

Stomatal conductance, which is crucial for plant carbon assimilation and water regulation, is modulated by Ca2+-binding proteins (CBPs). These proteins mediate Ca2+ signaling transduction, transport and homeostasis, influencing various physiological processes including stomatal movement, pollen tube growth and hypocotyl elongation. Despite their significance, the involvement of CBPs in dark-induced stomatal closure remains elusive. Here, we investigated the role of Arabidopsis cytosolic Ca2+-binding protein 1 (CCaP1) in dark-induced stomatal closure. &#x3b2;-glucuronidase (GUS) staining and in situ hybridization confirmed its predominant expression in guard cells. Yeast one-hybrid and transient expression assays demonstrated that CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) directly binds to the CCaP1 promoter to negatively regulate its expression. Genetic studies demonstrated that CCaP1 regulated dark-induced stomatal closure. Furthermore, the use of the Ca2+ probe R-GECO1 has shown that CCaP1 affected cytosolic free Ca2+ ([Ca2+]cyt) levels and potassium ion (K+) uptake in guard cells under dark conditions. Our findings indicate that CCA1-regulated CCaP1 is essential for maintaining Ca2+ dynamics and normal K+ flux in dark-induced stomatal closure.

To report a case of AA developing during golimumab and leflunomide treatment for seropositive rheumatoid arthritis, with subsequent improvement following initiation of selective Janus kinase 1 (JAK1) inhibition. A 55-year-old woman developed progressive, non-scarring alopecia while rheumatoid arthritis disease activity remained well controlled. Clinical and trichoscopic findings were consistent with AA, and laboratory investigations were unremarkable. The patient received serial intralesional triamcinolone at approximately 4-8&#x2009;week intervals over a 14-month period, with progression in Severity of Alopecia Tool (SALT) score from approximately 20 to 50. Alopecia developed and progressed despite ongoing TNF-&#x3b1; inhibitor therapy and serial intralesional corticosteroids. Upadacitinib was initiated for rheumatoid arthritis management and escalated from 15&#x2009;mg to 30&#x2009;mg. Hair regrowth was observed within six weeks, with SALT improving to approximately 15 by three months. Although spontaneous remission and delayed corticosteroid effects cannot be excluded, the timing and magnitude of improvement support a temporal association with JAK1 inhibition. This case highlights a pragmatic therapeutic consideration when alopecia arises during TNF-&#x3b1; inhibitor therapy.

There is broad consensus that successful repair of severe peripheral nerve injuries requires recreating key structural and cellular features of the natural regenerative process, particularly the action of Bands of B&#xfc;ngner (BoB), longitudinal Schwann cell (SC) structures that guide regenerating axons. Current biomaterial-based strategies have shown limited efficacy, in part because they do not sufficiently reproduce the anisotropic and cellular microenvironment established by BoB, resulting in disorganized axonal growth and reduced regenerative efficiency across long gaps. To address this limitation, a biohybrid scaffold designed to promote Schwann cell self-organization into B&#xfc;ngner-like structures through defined physical cues. Rather than relying solely on biochemical supplementation is developed, this system leverages anisotropic fiber architecture to induce SC alignment and early activation-associated phenotypic modulation. In this study, a self-organizing biohybrid BoB (BBoB) construct formed by Schwann cells within an aligned fiber-based scaffold is presented. It is demonstrated that these engineered structures recapitulate key morphological features of native BoB in vitro and promote enhanced axonal regeneration across a 11&#xa0;mm sciatic nerve defect in vivo. Together, these findings support the concept that physically programmed Schwann cell organization within biomaterial conduits can enhance peripheral nerve regeneration, using clinically accessible biomaterials and autologous Schwann cells.

Physiological palpation serves as a primary clinical modality for identifying pathological changes in tissue compliance. However, its diagnostic precision is inherently limited by the subjective nature of human haptic perception and the lack of quantifiable mechanical metrics. This work describes a bio-inspired, portable tactile interface engineered for the non-invasive and real-time characterization of tissue stiffness. The system incorporates multimodal piezoresistive sensing elements that emulate the specific mechanotransduction functions of cutaneous receptors, namely Merkel disks and Ruffini endings. By integrating Hertzian contact mechanics to decouple pressure and strain signals, the platform analytically derives the effective Young's modulus of heterogeneous soft tissues. The developed sensor architecture exhibits a functional range of 0-600 kPa and a gauge factor of 10.8, facilitating high-fidelity detection of subcutaneous anomalies. Validation against various nodule geometries and depths demonstrates that the system achieves a diagnostic resolution surpassing conventional manual assessments. Furthermore, the integration of wireless data processing enables instantaneous, on-site mechanical profiling. This platform provides a scalable framework for objective diagnostics, robotic haptics, and continuous physiological monitoring, establishing a robust bridge between qualitative clinical observation and quantitative biomechanical analysis.

The prognostic impact of worsening renal function (WRF) during the vulnerable phase following discharge after hospitalization for acute decompensated heart failure (HF) remains unclear. This study investigated the determinants of WRF 1&#x2009;year after discharge (1Y-WRF) and its association with clinical outcomes in patients with acute decompensated HF. Data were analyzed for 1753 patients hospitalized with acute decompensated HF from WET-HF2 (West Tokyo Heart Failure 2), a multicenter registry. 1Y-WRF was defined as a &#x2265;25% decrease in estimated glomerular filtration rate (eGFR). The primary end point was a composite of all-cause mortality and HF rehospitalization beyond 1&#x2009;year after discharge. Exploratory subgroup analyses were conducted based on age, sex, left ventricular ejection fraction, diabetes, eGFR, HF rehospitalization, and loop diuretic intensification within 1&#x2009;year after discharge, anemia, and renin-angiotensin-aldosterone system inhibitors&#xa0;use. Of the 1753 patients (median age 76&#x2009;years, 39.9% female, median eGFR 50.7&#x2009;mL/min per 1.73&#x2009;m2 at discharge), 285 (16.3%) developed 1Y-WRF. Female sex, anemia, higher New York Heart Association class, and higher eGFR at discharge were associated with 1Y-WRF. Over a median follow-up of 1&#x2009;year, 1Y-WRF was associated with an increased risk of the composite end point (adjusted hazard ratio, 1.34 [95% CI, 1.02-1.75], P=0.035), primarily driven by HF rehospitalization. The adverse prognostic impact was notable in young patients and those with high eGFR and no HF rehospitalization within 1&#x2009;year after discharge. In a contemporary cohort of acute decompensated heart failure 1Y-WRF was relatively common and associated with subsequent worse clinical outcomes.

Cholangiocarcinoma (CCA) is a malignant neoplasm arising from the biliary epithelium and is associated with an exceptionally poor prognosis. Metastasis to long bones is particularly uncommon. A 66-year-old male patient developed femoral metastasis 2&#x202f;years following a pancreaticoduodenectomy for distal cholangiocarcinoma and subsequently underwent total knee arthroplasty. He experienced a satisfactory postoperative recovery, with a marked enhancement in mobility. This case suggests that radical surgical intervention may be a viable option for metastatic bone disease characterised by isolated lesions. As illustrated in this instance, this therapeutic approach can alleviate symptoms and enhance the quality of life for the remaining duration.

The bodies of animals host millions of microbial communities collectively known as the microbiome. The microbiome plays a crucial role in various processes related to the host's health and well-being. Although our understanding of the microbiome's importance to host functioning is growing rapidly, many aspects remain poorly understood. One such aspect is the role of the microbiome in chemical communication. To address this question, we used the sand lizard (Lacerta agilis), a reptile with well-developed chemosensory abilities and commonly distributed in Central Europe. Our first goal was to characterize the bacterial microbiome associated with different body parts potentially involved in chemical signalling (e.g., femoral glands, cloaca, and skin). Additionally, we examined sex-related differences in the microbiome that could be connected to intraspecific communication. Over two years, a total of 274 samples were collected. Amplicon sequencing of the 16S rRNA V3-V4 region revealed significant variation in microbial diversity across body parts, with the skin hosting the most diverse and balanced communities. In contrast, the cloaca and femoral glands contained less diverse but more specialised assemblages. No differences in microbial diversity between sexes were observed, but the year of sampling was an important factor, suggesting a highly dynamic microbiome in sand lizards. There was minimal overlap in the number of unique operational taxonomic units (OTUs) between body parts, indicating a small core microbiome (&#x223c;1% of shared taxa). Sex differences in tissue-specific bacteria were more pronounced in the cloaca, supporting the idea that the cloacal microbiome is highly specialised. Our findings suggest that microbial communities vary significantly among body parts, with strong tissue specificity, indicating that each region provides a distinct ecological niche. This study offers promising directions for future research into how host-associated microbiomes could influence chemical communication in vertebrates.

Beh&#xe7;et's disease (BD) is a rare, multisystem inflammatory disorder predominantly affecting women during their reproductive years. Its potential impact on pregnancy outcomes makes understanding optimal management strategies crucial. Given the complexity and variability of this disease during pregnancy, there is a compelling need to review current evidence to guide clinical practice and improve maternal and neonatal outcomes. This narrative review consolidates recent literature from database inception to June 2025, focusing on disease course, reproductive implications, and obstetric outcomes in women with BD. It evaluates the safety of immunosuppressive therapies during conception, pregnancy, and lactation. The review highlights key aspects such as preconception planning, disease monitoring, delivery considerations, and postpartum care, drawing from a broad spectrum of clinical research, guidelines, and expert opinions. The current evidence suggests that with personalized, multidisciplinary care and careful medication management, many women with BD can experience successful pregnancies. While existing data support the safety of several therapies and highlight the importance of preconception counseling, significant gaps remain due to limited high-quality prospective studies. Advancements in understanding disease mechanisms, developing standardized protocols, and establishing evidence-based guidelines are necessary to optimize care and further improve reproductive outcomes in this patient population.

Second harmonic generation (SHG) is a widely used nonlinear optical process for frequency conversion and quantum information processing. However, existing approaches to enhance SHG in metasurfaces that are based on quasi-bound state in the continuum (quasi-BIC) resonances are often constrained by the limited second-order nonlinear susceptibilities of materials and the practical challenge of achieving high quality (Q) factors. Here, an alternative strategy is proposed to enhance SHG by increasing the absorptance (A) at the quasi-BIC resonance. Using temporal coupled mode theory (TCMT), an analytical expression is derived to link SHG intensity with both the resonance Q factor and absorptance, showing that strong SHG can be achieved even with finite Q when absorptance is properly optimized. To validate this concept, a 3R phase of molybdenum disulfide (3R-MoS2) metasurface is designed and fabricated by spectrally aligning a reflective resonance with a transmitted quasi-BIC mode, thereby enhancing absorptance at the target wavelength. The metasurface exhibits an SHG conversion efficiency of &#x223c;3 &#xd7; 10-5 at 9 GW cm-2, corresponding to more than 40-fold enhancement over an unpatterned flake. Despite the reduced damage threshold, the experimental results agree well with the theoretical model and establish a general design framework for absorptance-engineered metasurfaces for SHG.

Acute ischemic stroke (AIS) triggers a complex systemic immune-inflammatory response. While proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provide significant lipid-lowering and pleiotropic anti-inflammatory effects, their impact on early peripheral inflammatory and immune responses in AIS patients due to large artery atherosclerosis (LAA) remains underexplored. A total of 72 AIS patients attributed to LAA were included in the final analysis of this prospective study (the standard treatment group, n = 24; the intensive treatment group, n = 48). Fasting blood samples were obtained at admission and the 2-week follow-up. A comprehensive panel of laboratory parameters was assessed at baseline and the 2-week follow-up, encompassing lipid profiles, a spectrum of inflammatory biomarkers (including but not limited to high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-&#x3b1; (TNF-&#x3b1;)), and lymphocyte subsets. The intensive treatment group achieved a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) compared to the standard treatment group (P < 0.001). Notably, the intensive treatment group also showed significant reductions in key pro-inflammatory cytokines IL-6 (P = 0.024) and TNF-&#x3b1; (P = 0.041). However, no significant between-group differences were observed in the changes of peripheral blood lymphocyte subsets (P > 0.050). In AIS patients, early adjunctive PCSK9 inhibitor therapy provides superior lipid-lowering and may modulate specific pro-inflammatory cytokines compared to statin monotherapy, without significantly altering peripheral lymphocyte subset distributions within 2 weeks. Further large-scale studies are warranted to validate its immunomodulatory role and long-term clinical outcomes. ClinicalTrials.gov NCT05410457. Registered May 24, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05410457; ClinicalTrials.gov NCT05397405. Registered May 23, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05397405. Acute ischemic stroke (AIS) triggers a complex systemic immune-inflammatory response. While proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provide significant lipid-lowering and pleiotropic anti-inflammatory effects, their impact on early peripheral inflammatory and immune responses in AIS patients due to large artery atherosclerosis (LAA) remains underexplored. Our study evaluated the early immunomodulatory effects of PCSK9 inhibitor add-on therapy versus statin monotherapy in acute ischemic stroke patients. The combination therapy achieved superior LDL-C reduction and significantly decreased key pro-inflammatory cytokines (IL-6 and TNF-&#x3b1;), while no significant impact on peripheral lymphocyte subset distributions was observed within 2 weeks.