Wiley最新文献

{"title":"Adsorption Mechanism of Methyl Orange on MgAlCO3 Layered Double Hydroxide via Computational Modeling","authors":"S. Houmani,&nbsp;M. Khnifira,&nbsp;M. Elmouftari,&nbsp;F. Kzaiber,&nbsp;A. Oussama,&nbsp;N. Barka,&nbsp;M. Abdennouri,&nbsp;Gomaa A. M. Ali,&nbsp;F. Z. Mahjoubi","doi":"10.1002/slct.202502497","DOIUrl":"https://doi.org/10.1002/slct.202502497","url":null,"abstract":"<p>This study investigates the adsorption mechanism of methyl orange (MO) onto MgAlCO₃ layered double hydroxide (LDH) in an aqueous solution using density functional theory (DFT) computations. Chemical descriptors, including frontier molecular orbital energies (<i>E</i>_HOMO, <i>E</i>_LUMO), energy gap (<i>ΔE</i>_gap), electronegativity (<i>χ</i>), hardness (<i>η</i>), softness (S), and transferred electron fraction (<i>ΔN</i>) were analyzed. The low <i>E</i>_LUMO value (−2.456 eV) suggests high adsorption capacity, further supported by the small energy gap (4.421 eV), indicating potential covalent bond formation with LDH. Lower hardness and higher softness values suggest facile electron sharing by MO, leading to strong interaction with LDH. Elevated electronegativity and <i>ΔN</i> for neutral MO imply its ability to donate electrons to the LDH surface. Negative back–donation energy (<i>ΔE</i>_{back-donation}) indicates favorable electron back-donation from MO to LDH. DFT results suggest high MO reactivity, facilitating interaction with LDH. Molecular dynamics simulations reveal a parallel orientation of MO above the LDH surface. Adsorption energy calculations indicate stronger adsorption for neutral MO (−599.044 kcal/mol) compared to ionic MO (−369.913 kcal/mol), suggesting preferential adsorption of the neutral form. The adsorption process is identified as chemisorption and spontaneous.</p>","PeriodicalId":146,"journal":{"name":"ChemistrySelect","volume":"10 35","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Eating Window With Mortality Among US Adults: Insights From a Nationally Representative Study.","authors":"Ziling Mao, Haley Grant, Stephen B Kritchevsky, Anne B Newman, Samaneh Farsijani","doi":"10.1111/acel.70230","DOIUrl":"https://doi.org/10.1111/acel.70230","url":null,"abstract":"<p><p>Time-based diets have gained popularity for their health benefits, but their effects on human longevity remain unclear, with most evidence from short-term human trials and animal studies. We determined the associations between eating window and mortality among U.S. adults. We conducted a prospective cohort study using NHANES 2003-2018 data linked to mortality records through December 2019. The analytic sample included 33,052 adults (aged 20 and above) with two complete 24-h dietary recalls collected at baseline. Eating window was defined as the time between first and last consumption of any food/beverage containing > 0 kcal within 24 h. We used survey-weighted Cox regression with Restricted Cubic Splines (RCS) to model nonlinear associations, treating eating window as both a continuous and categorical variable (< 8.0-≥ 15.0 h/day). Models were adjusted for sociodemographic, lifestyle, health, and dietary factors. Subgroup analyses were conducted by age, sex, and race/ethnicity. Over a median follow-up of 8 years, there were 4158 all-cause, 1277 cardiovascular, and 989 cancer deaths. RCS models showed a U-shaped association between eating window and mortality, with the lowest risk at ~11-12 h/day (p = 0.004). Shorter windows (≤ 8 h) were linked to ≥ 30% higher all-cause mortality, especially in older adults, and > 50% higher cardiovascular mortality in older adults, men, and Whites. Longer eating window categories (≥ 15 h/day) were associated with 25% higher all-cause mortality (95% CI: 1.01-1.55). Moderate eating windows (~11-12 h/day) are linked to the lowest mortality risk, with deviations associated with higher risk. Differences across demographic groups highlight the need for personalized guidance.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70230"},"PeriodicalIF":7.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox-Active Nanozymes in Metabolic Modulation for Precision Therapeutics.","authors":"Wenying Zhang, Meifang Wang, Ping'an Ma, Jun Lin","doi":"10.1002/adhm.202502110","DOIUrl":"https://doi.org/10.1002/adhm.202502110","url":null,"abstract":"<p><p>Nanozyme metabolic therapy leverages the catalytic activity of artificial enzymes to reprogram dysregulated metabolic pathways at disease sites, offering a targeted approach to restore physiological homeostasis. This review uniquely focuses on redox-active nanozymes and their roles in modulating key metabolic circuits (e.g., glucose, lactate, lipid, and xanthine metabolism) across diverse pathological contexts. While cancer remains the most extensively explored domain, emerging uses of nanozymes in bacterial infections, cardiovascular diseases, diabetes, obesity, and inflammatory disorders, where mechanistic understanding is still evolving, are also highlighted. By selectively altering metabolite levels and enzymatic activities, nanozymes enable precise metabolic control with high catalytic specificity. Nanozymes are systematically categorized based on their redox mechanisms and the metabolic pathways they influence, and discuss representative examples across disease contexts. Finally, the review concludes by outlining current challenges and emphasizing the translational potential of nanozymes as programmable metabolic modulators, aiming to expand their impact beyond oncology into broader clinical applications.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02110"},"PeriodicalIF":9.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Millimetre-Wave Microstrip Patch Antenna With Stable Wide Beamwidth for Wide-Angle Scanning","authors":"Lei Wang,&nbsp;Guo Xing Xu,&nbsp;Hai Yang Yao,&nbsp;Zhao Feng Chen,&nbsp;Wei Bin Kong,&nbsp;Feng Zhou","doi":"10.1049/mia2.70047","DOIUrl":"https://doi.org/10.1049/mia2.70047","url":null,"abstract":"<p>A millimetre-wave (mm-wave) microstrip patch antenna with a stable wide beamwidth is proposed for a wide-angle scanning phased array. The proposed antenna element is achieved by loading four semi-open parasitic elements around the stacked patch. The four semi-open parasitic elements can generate two pairs of stable antiphase current radiation sources to achieve a stable rotated ‘8’-shaped pattern, which can obtain wide-beamwidth radiation patterns when it is synthesised with the broadside radiation pattern produced by the stacked patch. Further, the coupling between the parasitic elements and the driven patch producing the lower reflection zero is weaker than that between the parasitic patch producing the upper reflection zero. Therefore, the proposed antenna can achieve a stable wide beamwidth over wide frequency ranges. The generation of the rotated ‘8’-shaped pattern is theoretically analysed. An eight-element <i>E</i>-plane scanning linear antenna array based on the proposed antenna element is demonstrated for the potential application in a wide-angle scanning phased array. The simulated and measured results show that the main beam can scan from −75° to 75° with a gain fluctuation &lt; 3 dB under a 10-dB fractional bandwidth of 16.7%.</p>","PeriodicalId":13374,"journal":{"name":"Iet Microwaves Antennas & Propagation","volume":"19 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/mia2.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"计算机科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kisspeptin-10 Improves Gestational Diabetes Mellitus Symptoms in Rats by Suppressing Insulin Resistance in Placental Trophoblast Cells by Activating the Cyclic AMP/Protein Kinase A Pathway","authors":"Jianhua Li,&nbsp;Jinhuan Chen,&nbsp;Lin Lu,&nbsp;Bei Gan","doi":"10.1111/cbdd.70169","DOIUrl":"https://doi.org/10.1111/cbdd.70169","url":null,"abstract":"<div>\u0000 \u0000 <p>Gestational diabetes mellitus (GDM) is a common pregnancy complication that leads to insulin resistance (IR) and adversely affects both maternal and fetal health. Kisspeptin-10 (Kp-10), a peptide acting via G Protein-Coupled Receptor 54 (<i>Gpr54</i>), has shown potential in modulating insulin secretion, but its role in GDM remains unclear. This study explores Kp-10's therapeutic effects on GDM by targeting IR in placental tissues. We used GDM rat models (induced by a high-fat diet and streptozotocin) and high-glucose-treated HTR8/SVneo trophoblast cells to investigate Kp-10's effects on glucose metabolism, insulin signaling, and the cAMP/PKA pathway. Our results show that <i>Gpr54</i> expression was significantly downregulated in the placental tissues of GDM rats, which was associated with impaired glucose uptake and IR. Kp-10 treatment improved fasting blood glucose (FBG) levels, insulin sensitivity, and fetal outcomes, including increased fetal weight and decreased fetal blood glucose. Moreover, Kp-10 restored the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway and enhanced glucose uptake by upregulating <i>Glut</i>-<i>4</i>, <i>Insr</i>, and <i>Irs1</i> expression in both placental tissues and HTR8/SVneo cells. The effects of Kp-10 were reversed by the cAMP inhibitor SQ22536, confirming the involvement of the cAMP/PKA pathway in its anti-IR effects. Our findings suggest that Kp-10 has the potential as a therapeutic agent for alleviating IR in GDM and improving maternal–fetal outcomes.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UCLP: Unsupervised Classification of Key Aspects in Vulnerability Descriptions Through Label Profile","authors":"Linyi Han,&nbsp;Hang Li,&nbsp;Xiaowang Zhang,&nbsp;Youmeng Li,&nbsp;Zhiyong Feng","doi":"10.1002/smr.70052","DOIUrl":"https://doi.org/10.1002/smr.70052","url":null,"abstract":"<div>\u0000 \u0000 <p>Textual vulnerability descriptions (TVDs) in repositories like NVD and IBM X-Force Exchange are essential for security engineers managing vulnerabilities. Engineers typically search for key aspects in TVDs using specific phrases, but with multiple expressions for each aspect, retrieving all relevant records is challenging. We propose a label-based retrieval framework that classifies key aspects and retrieves TVDs by their broader categories. Given the large data volume, manual labeling is infeasible, making unsupervised classification critical. However, short labels and repeated words diminish semantic clarity, affecting classification accuracy. We introduce Unsupervised Classification through Label Profile (UCLP), which expands label semantics through label profiles inspired by recommendation systems. We construct profiles using neural network weights and apply TF-IDF to calculate similarities, smoothing distributions with an arctangent function. Results show that UCLP significantly outperforms four benchmarks, raising accuracy from 68.3% to 78.9% and improving three real-world applications.</p>\u0000 </div>","PeriodicalId":48898,"journal":{"name":"Journal of Software-Evolution and Process","volume":"37 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"计算机科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane Lipid Remodeling Strategies Regulate Fluidity for Acute Temperature Adaptation in Oysters","authors":"Mingyang Du,&nbsp;Jincheng Chen,&nbsp;Chaogang Wang,&nbsp;Zhuxiang Jiang,&nbsp;Min Wang,&nbsp;Meiqian Pang,&nbsp;Tian Bu,&nbsp;Rihao Cong,&nbsp;Wei Wang,&nbsp;Guofan Zhang,&nbsp;Li Li","doi":"10.1111/eva.70156","DOIUrl":"https://doi.org/10.1111/eva.70156","url":null,"abstract":"<p>Extreme climatic temperature stress induced by global warming poses a severe threat to the survival of marine invertebrates. The plasma membrane functions as a natural barrier and serves as the first responder to ambient temperature through dynamic modulation of its fluidity. However, the adaptive mechanisms of membrane lipid remodeling in response to temperature fluctuations remain poorly understood in marine organisms. Oysters, the most widely cultivated shellfish globally, hold significant economic and ecological importance. We characterized the changes in plasma membrane lipid composition of two congeneric oyster species—the northern/cold-adapted <i>Crassostrea gigas</i> and the southern/warm-adapted <i>Crassostrea angulata</i>—under short-term acute heat and cold stress, including changes in lipid subclass content, glycerophospholipid acyl chain length, and glycerophospholipid unsaturation. Our results revealed sphingolipids and sterol lipids content may play a more critical role in short-term temperature adaptation, while glycerophospholipid alterations may prioritize dynamic lipid modifications over abundance changes. Notably, the relatively cold tolerant <i>C. gigas</i> exhibited higher lipid unsaturation and shorter acyl chain lengths, with a preferential modulation of glycerophospholipid acyl chain length, while the heat tolerant <i>C. angulata</i> regulated fatty acid unsaturation to maintain membrane fluidity for temperature adaptation. Divergent membrane lipid remodeling strategies in two congeneric oysters provide new insights into the adaptation mechanisms of membrane fluidity in marine organisms, informing risk assessment for aquaculture industries under global warming. The identification of key components such as phosphatidylethanolamine, sphingosine, ceramide phosphates, and cold and heat adapted lipid molecules provides important biomarkers for predicting the adaptive potential of marine organisms to future extreme climate.</p>","PeriodicalId":168,"journal":{"name":"Evolutionary Applications","volume":"18 9","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eva.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Regression Grade as a Predictor of Adjuvant Therapy Benefits in Esophageal Squamous Cell Carcinoma Patients After Neoadjuvant Therapy","authors":"Yizhou Huang,&nbsp;Maohui Chen,&nbsp;Yuanpu Wei,&nbsp;Bingqiang Cai,&nbsp;Yongcong Zhang,&nbsp;Chuanquan Lin,&nbsp;Shuliang Zhang,&nbsp;Taidui Zeng,&nbsp;Chun Chen,&nbsp;Bin Zheng","doi":"10.1002/cam4.71166","DOIUrl":"https://doi.org/10.1002/cam4.71166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neoadjuvant therapy followed by surgery is preferred for locally advanced esophageal squamous cell carcinoma (ESCC), but the necessity of adjuvant therapy remains controversial. Tumor regression grade (TRG) reflects the response to neoadjuvant therapy and may predict patient prognosis, yet its role in guiding adjuvant therapy remains unexplored. This study aimed to explore the role of TRG and other clinical characteristics in predicting the efficacy of postoperative adjuvant therapy in ESCC patients receiving neoadjuvant therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included patients who underwent R0 esophagectomy for thoracic ESCC after neoadjuvant therapy between January 2016 and December 2021 across three high-volume centers. Patients were assessed by TRG and divided into good responders (TRG 0–1) and poor responders (TRG 2–3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 416 patients with a median follow-up of 52 months, adjuvant therapy extended median survival by 8 months, which was statistically insignificant (<i>p</i> = 0.28). In the TRG 0–1 subgroup, those receiving adjuvant therapy had 3-year and 5-year OS rates of 94.6% and 86.8%, compared to 78.8% and 71.6% for the observation group (<i>p</i> = 0.02). Multivariable Cox regression showed adjuvant therapy was associated with reduced mortality in the TRG 0–1 (HR 0.32; 95% CI 0.14–0.73; <i>p</i> = 0.006), positive lymph nodes (HR 0.53; 95% CI 0.36–0.78; <i>p</i> = 0.001), and ypT3-4 subgroups (HR 0.63; 95% CI 0.43–0.92; <i>p</i> = 0.017).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>TRG is a promising predictor of the prognostic value of adjuvant therapy in ESCC patients. Patients with a good TRG response, positive lymph nodes, and ypT3-4 stage benefit from adjuvant therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 18","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front Cover: Development and Recent Advances in SLIPT-PM: A Chemogenetic Platform for Manipulating Signaling at the Plasma Membrane (ChemBioChem 16/2025)","authors":"Shuya Ohira,&nbsp;Akinobu Nakamura,&nbsp;Kenta Terai,&nbsp;Shinya Tsukiji","doi":"10.1002/cbic.70016","DOIUrl":"https://doi.org/10.1002/cbic.70016","url":null,"abstract":"<p>SLIPT-PM is a chemogenetic technique that enables the inducible translocation of specific tag-fusion proteins to the plasma membrane (PM) in living cells by using a synthetic self-localizing ligand (SL). This user-friendly method allows researchers to manipulate a wide range of intracellular signaling molecules and pathways with controlled reversibility and repeatability. In 10.1002/cbic.202500327, Shinya Tsukiji and co-workers review the development, key features, current applications, and future challenges of SLIPT-PM as a unique tool in chemical and synthetic biology. Cover art by Hiroko Uchida.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Molecular Genetic Characterization of Landau Kleffner Syndrome: An Observational Cohort and Experimental Study.","authors":"Adeline Ngoh, Maria Clark, Rebecca Greenaway, Xiumin Chen, Kimberley M Reid, Katy Barwick, Esther Meyer, Dale Moulding, Natalie Trump, J Helen Cross, Sean D Fraser, Lachlan de Hayr, Dimitri M Kullmann, Joseph W Lynch, Robert J Harvey, Manju A Kurian","doi":"10.1002/ana.27306","DOIUrl":"https://doi.org/10.1002/ana.27306","url":null,"abstract":"<p><strong>Objective: </strong>Landau-Kleffner syndrome (LKS), is a rare, poorly-understood epileptic encephalopathy with spike-wave activation in sleep associated with mutations in GRIN2A, encoding the N-Methyl-D-Aspartate receptor (NMDAR) GluN2A subunit. Physicians rely on empirical treatments, with scarce information on treatment efficacy and outcomes. This study aims to improve the understanding and clinical management of LKS.</p><p><strong>Methods: </strong>Fifty-two patients with LKS were recruited via one quaternary referral center. Case-notes review delineated clinical features, long-term outcomes, and prognostic factors. Generalized estimating equations were used to determine the longitudinal association among electroencephalogram abnormalities, steroid therapy, and neuropsychological findings. After genetic screening, the impact of identified GRIN2A missense variants on NMDAR function was assessed using homology modeling, cell-surface trafficking assays, and electrophysiology in artificial synapses. Whole exome/genome sequencing was performed on GRIN2A-negative patients to identify novel gene associations.</p><p><strong>Results: </strong>LKS is complex with significant clinical and genetic heterogeneity. Besides speech and language impairment, many patients had other co-morbidities and almost half have long-term disability. Early age at disease onset was associated with worse outcomes. There was no reliable correlation between electroencephalogram findings and developmental scores. Steroid therapy improved language outcomes independently of electroencephalogram findings. GRIN2A mutations were identified in 15.5% of the cohort. Likely pathogenic variants in GABBR2, SCN1A, TRPC1, ERRFI1, CTXN3, IRX6, and IQCA1 were identified in 7 GRIN2A-negative individuals.</p><p><strong>Interpretation: </strong>For LKS, early intervention is important for long-term outcomes. Furthermore, management should not be based solely on electroencephalogram findings. Genetic and functional investigations offer insights into disease pathophysiology and facilitate development of future targeted therapies. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}