Metabolic dysregulation has been recognized as a crucial driver of tumorigenesis, particularly in metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC). However, the underlying mechanisms remain poorly understood. Here, we identify lysosome-localized insulin receptor tyrosine kinase substrate (IRTKS) as a key activator of the metabolic master regulator mTORC1 through phospho-antibody array screening. IRTKS forms membrane-associated condensates that selectively interact with the GTPase RRAGD, a key upstream regulator of mTORC1, thereby enhancing the sensitivity of mTORC1 to free amino acids. Notably, in hepatic knockin mice, Irtks-mediated mTORC1 hyperactivation promotes obesity, hepatic lipid accumulation, and the progression from MASLD to metabolic dysfunction-associated steatohepatitis and HCC. Conversely, pharmacological inhibition of mTORC1 or genetic ablation of Irtks ameliorates hepatic steatosis, inflammation, and metabolic dysfunction in mouse models. Our study establishes IRTKS as a central regulator of mTORC1-dependent metabolic reprogramming during hepatocarcinogenesis, providing potential therapeutic targets for MASLD-associated liver cancer.

Tumor is generally believed to originate from a single cell, which develops into a genetically heterogeneous population after continuous cell divisions under the principle of “survival of the fittest”. Tumor evolution is a dynamic process, and reconstruction of the disappeared history is challenging but crucial for both understanding the mechanism and personalized therapy. Genetic alterations can be used as molecular clues to tumor evolution, with somatic mutations as a key tracer. Although bulk-level sequencing of a large number of tumor specimens has provided useful information on the mutational landscape, it is not easy to utilize such data for evolutionary history study. This is because bulk-level mutation prevalence may be confounded by various factors, such as tumor purity, copy number alterations, and more severely, the overlapping of prevalence ranges for mutations from similarly sized subclones. Single-cell mutational profiling overcomes such challenges, enabling precise identification of co-mutation groups and tumor subclones. This further enables successful reconstruction of tumor evolution, even for a solid tumor sample collected at a single time point. Technical and analytical advancements in single-cell profiling, such as mutation calling from single-cell RNA-Seq or spatial transcriptomic data, will provide further insights into tumor evolution and cancer treatment.

BackgroundCystic fibrosis (CF) is a rare autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although relatively common in Caucasian populations, CF is rare in China, where it frequently presents with non-specific respiratory symptoms, leading to delayed diagnosis and frequent coinfections with multidrug-resistant pathogens.Case reportA 21-year-old man presented with a 6-year history of recurrent productive cough and intermittent fever over the past 6 months. Imaging revealed bronchiectasis with evidence of infection. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid identified Staphylococcus aureus and Mycobacterium abscessus. Further investigations revealed pancreatic lipomatosis, congenital absence of seminal vesicles, and fat-soluble vitamin deficiencies. CF diagnosis was confirmed by elevated sweat chloride concentration (88 mmol/L) and biallelic CFTR mutations. Clinical stability was achieved through a quadruple antimycobacterial regimen (linezolid, moxifloxacin, azithromycin, and minocycline) combined with systemic supportive care. CFTR modulator therapy was deferred due to limited access and financial constraints.ConclusionWe report a case of CF in a Chinese patient presenting with nontuberculous mycobacterial infection, a condition rarely documented in East Asian populations. We provide a review of the relevant literature, aiming to emphasize the importance of early recognition of CF, personalized antimicrobial strategies, and improved access to essential medications.

Bronchopleural fistula (BPF), defined as a pathological communication between the bronchial airways and the pleural space, carries high mortality (18%-50%) due to complications like infection and respiratory failure. Current treatments, including conservative management and invasive surgery, face limitations such as variable efficacy, high trauma, and inapplicability to high-risk patients. An innovative bronchoscopy-guided petrolatum gauze occlusion protocol provides a minimally invasive, cost-effective solution for patients with small to medium-sized bronchopleural fistulas (≤5 mm) who are not candidates for surgery. Key steps included precise fistula localization via. methylene blue dilution injection, tailored gauze sizing, and bronchoscopic placement under direct visualization. Stability was ensured through forceps-guided positioning or supplemental metal stents in anatomically challenging cases. Post-procedure monitoring included chest X-ray, CT imaging, and clinical assessments at 1 day, 1 week, and 1 month. In a retrospective study of 19 patients with peripheral BPFs ≤ 5 mm who met predefined inclusion criteria (e.g., failed prior conservative therapy, high surgical risk) and exclusion criteria (e.g., untreated empyema, fistulas involving central airways), petrolatum gauze occlusion achieved 94.7% efficacy (18/19) at one week, with a low infection rate (15.8%). The observed efficacy, while promising, should be interpreted within the context of the study's limitations, including its small sample size (n = 19), single-center retrospective design, and potential for selection bias. Consequently, the generalizability of these findings to broader patient populations or other institutional settings may be limited. This cost-effective, adaptable technique demonstrates high success in sealing small-to-medium fistulas (≤5 mm), offering a safe alternative for high-risk populations, particularly in resource-limited settings. This article describes in detail the indications for this method, preoperative evaluation, intraoperative manipulation, and postoperative testing.

Hepatic fibrosis, caused by liver damage from various sources, involves excessive ECM deposition, disrupting liver function and leading to cirrhosis and liver failure. Liver transplantation is the only definitive treatment but is limited by donor shortages, surgical risks, and high costs. There is an urgent need for alternative therapies that can halt fibrosis and improve targeted drug delivery. Electrochemical biosensors offer high sensitivity, selectivity, and portability for point-of-care testing. They detect biomarkers like liver enzymes, inflammatory markers, and fibrosis-related molecules, enabling early detection and monitoring of liver fibrosis. Preclinical studies show that NK cell-derived exosomes loaded with Galunisertib effectively target fibrotic cells, reducing collagen deposition and improving outcomes. Combining these nanotherapeutics with electrochemical sensors creates a precision medicine approach. Sensors guide treatment and monitor therapy responses in real time, enhancing diagnostic accuracy and personalization. This integration has significant potential to improve clinical outcomes in chronic liver disease, offering a transformative solution for diagnosing and managing liver fibrosis.

Background White matter hyperintensities (WMHs) represent a cardinal feature of cerebral small vessel disease (CSVD), yet iron dysregulation alterations within these lesions and their relationship to cognitive decline remains poorly understood. Objectives To characterize iron dysregulation in WMH using quantitative susceptibility mapping (QSM) and examine their relationship with CSVD severity and cognitive function. Design Cross-sectional study with longitudinal follow-up component. Setting Single-center study at Shandong Provincial Hospital Affiliated with Shandong First Medical University, China. Participants 299 participants recruited from January 2021 to September 2023, with 71 participants completing longitudinal follow-up (mean interval 20.6 months). Participants were categorized into early CSVD (0 points, n = 171), mild CSVD (1 point, n = 70), and severe CSVD (≥2 points, n = 58) groups based on total burden scoring. Intervention None (observational study). Measurements 3.0T MRI with quantitative susceptibility mapping and diffusion tensor imaging. Spatial analysis examined susceptibility values in WMH cores and perilesional zones (0–2 mm, 2–4 mm, 4–6 mm). Cognitive assessments included Montreal Cognitive Assessment (MoCA), Symbol Digit Modalities Test (SDMT), and other neuropsychological tests. Results WMH susceptibility values were significantly lower than normal-appearing white matter (-14.55 vs -7.77 ppb, P < 0.001) with progressive increases correlating with CSVD severity (P < 0.001). Cross-sectionally, higher WMH susceptibility values correlated with lower MoCA scores (r = -0.155, P = 0.045). Longitudinally, WMH susceptibility values predicted decline in information processing speed (SDMT: β = -0.247, P = 0.042). Spatial analysis revealed distinct patterns with perilesional regions showing intermediate susceptibility values. Conclusions Iron dysregulation alterations within WMH provide independent information about cognitive risk in CSVD. QSM emerges as a promising biomarker for monitoring cognitive trajectory and may facilitate early identification of patients at risk for cognitive decline.

This study aims to reveal the regulatory mechanism underlying the antagonistic effects of JDHY granules against ALF. The anti-inflammatory effect of JDHY granules was evaluated by observing hematoxylin-eosin staining of liver tissue sections and measuring serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) in rats. Label-free quantitative proteomics and untargeted metabolomics were employed to assess protein and metabolite changes in liver tissues before and after JDHY treatment in ALF rats. Differentially expressed proteins (DEPs) and metabolites (DEMs) were identified and analyzed bioinformatically. JDHY granules alleviate the pathological changes in liver tissue, reduce the levels of serum ALT, AST, and TBIL in ALF rats. Proteomic results suggested that there were 303 DEPs in model group and the JDHY granule group, which were enriched in pathways such as the PI3K-Akt signaling pathway, glycolysis, and gluconeogenesis. Metabolomic analysis identified 31 DEMs between the model and JDHY granule groups. These metabolites were enriched in pathways such as glycolysis and gluconeogenesis. Joint enrichment analysis of proteomics and metabolomics revealed significant enrichment of DEPs and metabolites DEMs in pathways such as glycolysis and gluconeogenesis. Moreover, parallel reaction monitoring validated the parallel changes of common DEPs in ALF liver, exhibiting consistent expression changes as observed in the proteomic analysis. The therapeutic efficacy of JDHY granules in ALF may involve PI3K-AKT pathway activation and inhibition of liver glycolysis, thereby alleviating hepatic inflammatory stress.

SCARA5 (Scavenger Receptor Class A Member 5), a member of scavenger receptor class A, is a type II transmembrane protein. Previous studies, including our own, have suggested that SCARA5 acts as a tumor suppressor in various cancers. Additionally, SCARA5 has been identified as a ferritin receptor that facilitates iron delivery independent of transferrin. However, it remains unclear whether ferroptosis is involved in the tumor-suppressive function of SCARA5 in hepatocellular carcinoma (HCC). In this study, we found that SCARA5-deficient cells, including mouse embryonic fibroblasts (MEFs) and HCC cells, exhibited reduced sensitivity to ferroptosis induced by erastin and RSL3. We measured the cell viability, cellular reactive oxygen species (ROS), lipid ROS, malondialdehyde (MDA) and ferrous iron concentration to assess the role of SCARA5 in ferroptosis. Mechanistically, we confirmed that SCARA5 might enhance the intracellular availability of bioactive ferrous iron by promoting autophagic degradation of the major iron storage protein ferritin. Furthermore, we found that SCARA5 deficiency contributed to the resistance of HCC cells to sorafenib, a therapeutic agent for HCC, possibly by inhibiting ferroptosis. Collectively, our study revealed the role of SCARA5 in regulating ferroptosis, providing a profound understanding of sorafenib resistance in HCC systemic therapy.

Bronchopleural fistulas (BPFs) are severe medical condition with high mortality. When the conventional surgical therapy failed, endobronchial intervention could function as the supplementary option. Several studies reported successful endobronchial managements of BPFs whereas the optimal strategies remain elusive. We retrospectively reviewed the medical records of patients with BPFs underwent endobronchial interventions with Vaseline gauze, shape-adjustable silicone plug, sutured silicone tube or covered metallic stent in our institution. From 2018 to 2024, a total of 30 patients (11 females VS. 19 males; mean age 48.03 ± 20.33 years) with primary etiology of tumor (n = 19), empyema (n = 6), gastro-bronchial fistula (n = 1), lung infection with immune suppressed status (n = 1) and spontaneous pneumothorax (n = 3) were treated. Different occlusive materials were placed including covered metallic stent (n = 6), shape-adjustable silicone plug (n = 4), sutured silicone tube (n = 1) and Vaseline gauze(s) (n = 21). The dislocation of devices occurred in two patients with covered metallic stent occlusion. On the first day post procedure, 17 patients (56.7

BACKGROUND:The susceptibility values of the basal ganglia reflect the health status of these nuclei. We aimed to explore the associations between various demographic characteristics, lifestyle factors, and biological factors that have the potential to contribute to magnetic susceptibility and investigate the comprehensive impact of these multiple factors on basal ganglia susceptibility values. METHODS:We included 25,980 participants from the UK Biobank. Linear regression analysis was employed to assess the relationship between basal ganglia susceptibility values and demographic characteristics (age, sex, ethnicity), lifestyle factors (tea consumption, coffee intake, smoking status, alcohol consumption, physical activity, insomnia status), and biological factors (C-reactive protein, blood cell counts, anthropometric measures, blood pressure parameters). RESULTS:Multiple factors demonstrated significant associations with basal ganglia iron deposition. Among biological factors, C-reactive protein showed significant positive correlations with susceptibility values in the caudate nucleus (β = 0.028, p < 0.001), globus pallidus (β = 0.046, p < 0.001), and substantia nigra (β = 0.031, p < 0.001). Waist circumference, another biological measure, had substantial positive effects on most basal ganglia regions (β = 0.115 in caudate, β = 0.122 in putamen, β = 0.058 in globus pallidus). Among lifestyle factors, current smoking status was significantly associated with increased susceptibility values across all four basal ganglia nuclei (β = 0.053-0.061, all p < 0.001). Tea consumption demonstrated dose-dependent protective effects, with daily consumption of ≥ 4 cups showing significant negative associations with all basal ganglia regions (-0.032 to -0.093 standard deviations). Age demonstrated significant positive associations with most basal ganglia regions. Gender differences were observed in tea consumption effects, with females showing stronger protective benefits (5.59 vs. 1.50 years of equivalent "rejuvenation" effect for 0-3 cups daily). CONCLUSIONS:We provide evidence for multiple demographic, lifestyle, and biological factors influencing brain iron deposition in healthy middle-aged and elderly individuals. Systemic inflammation, smoking, and increased adiposity were associated with greater iron deposition, while tea consumption showed protective effects. These findings highlight potential targets for interventions aimed at maintaining brain health. ETHICS APPROVAL AND CONSENT TO PARTICIPATE:The UK Biobank protocol was approved by the NHS North West Multicentre Research Ethics Committee (21/NW/0157). All participants provided informed consent at recruitment, allowing for follow-up using data linkage to health records.

BACKGROUND:Cerebral small vessel disease (CSVD) is associated with microstructural changes in subcortical gray matter linked to cognitive function. These changes may vary across different subregions. The aim of our study was to explore microstructural alterations in subcortical gray matter subregions associated with cognition in CSVD patients using magnetic resonance (MR) quantitative susceptibility mapping (QSM). METHODS:A total of 295 participants were included in the study, consisting of 112 healthy controls (HC), 85 with mild CSVD, and 98 with severe CSVD. All participants underwent MRI scans and cognitive function assessments. QSM images were segmented into 32 subcortical gray matter regions. Differences in susceptibility values across the three groups and their relationships with clinical and cognitive function were analyzed. RESULTS:After adjusting for potential confounders, the susceptibility values of the posterior part of the right hippocampus (pHIPr) (β = 1.209, P = 0.030) and the posterior part of the right caudate (pCAUr) (β = 4.373, P = 0.005) were positively correlated with CSVD severity. In the CSVD cohort, the mean susceptibility values of pCAUr were significantly associated with various cognitive functions. Furthermore, a simple mediation model demonstrated that the mean susceptibility value of pCAUr mediated the relationship between CSVD burden and SCWT score (indirect effect = 2.309, 95 % CI = 0.450-4.986, Pm = 21.5 %). CONCLUSION:Our study revealed a relationship between microstructural changes of subcortical gray matter in CSVD patients and cognitive function and highlighted the potential of QSM in detecting brain microstructural alterations associated with cognition.

ETHNOPHARMACOLOGY RELEVANCE:Jiedu Huayu Granules (JDHY), a compound formula of six traditional Chinese herbal medicines, has been used for nearly twenty years to treat acute liver failure (ALF) with good clinical efficacy. Its underlying drug mechanisms warrant in-depth exploration. AIM OF THE STUDY:This study aims to investigate the inhibitory effects and mechanisms of JDHY on D-Galactosamine + Lipopolysaccharides (D-GalN + LPS)-induced ALF cell and animal models in mice. MATERIALS AND METHODS:The 10 mg/mL D-GalN+1 μg/mL LPS-induced ALF cell model in mice was established according to previous methods, and 15 % JDHY-containing serum was used for intervention. Transcriptomics and proteomics analyses were employed to explore the effective mechanism of JDHY in treating ALF, and verification was carried out at the cell and animal levels based on the omics results. RESULTS:Transcriptomics revealed JDHY anti-ALF mechanism involves ferroptosis. Proteomics suggested 5-lipoxygenase (5-LOX) mediates JDHY anti-ferroptotic effects. Crucially, 5-LOX subcellular localization influences its activity: cytoplasmic retention exacerbates ALF oxidative stress and ferroptosis, which ferroptosis inhibitor Fer-1 significantly attenuated. Mechanistically, cAMP-PKA pathway activation promotes 5-LOX nuclear-to-cytoplasmic translocation. Conversely, JDHY inhibited cAMP-PKA expression, facilitated 5-LOX nuclear reflux, and alleviated ferroptosis-mimicking PKA siRNA effects. In addition, JDHY inhibition of ALF ferroptosis might be multifaceted, as we also found that it promoted the expression levels of Slc7a11, GSH, and GPX4, indirectly improving the antioxidant capacity of cells. CONCLUSION:JDHY suppresses 5-LOX-catalyzed lipid peroxidation via negative feedback regulation of the cAMP-PKA pathway, mitigating ALF-associated ferroptosis. Moreover, the data provided in this paper suggest that 5-LOX can serve as a potential target for inhibiting ALF ferroptosis, providing a scientific basis for the clinical prevention and treatment of ALF.

BACKGROUND:White matter (WM) microstructural deterioration is associated with a higher total cerebral small vessel disease (CSVD) burden, as assessed by magnetic resonance imaging (MRI) markers, and with more pronounced cognitive decline in CSVD patients. However, the relationships among CSVD burden, cognitive impairment and WM changes remain unclear. We aimed to characterize WM microstructural abnormalities in patients with different CSVD burdens and investigate the mechanism linking different CSVD burdens to cognitive decline. METHODS:This study included 56 patients with severe CSVD burden (CSVD-s), 109 patients with mild CSVD burden (CSVD-m) and 81 healthy controls. We used diffusion tensor imaging (DTI) and tract-based spatial statistics to detect WM diffusion changes between groups and then explored the relationships between different CSVD burdens, WM diffusion changes and cognitive function, especially to quantitatively analyze the possible mediating effect of WM microstructural alterations on CSVD burden and cognitive function. RESULTS:The CSVD-s group presented significantly decreased FA and increased AD, RD and MD in the forceps minor, bilateral anterior thalamic radiation (ATR), superior longitudinal fasciculus (SLF), corticospinal tract (CST) and inferior fronto-occipital fasciculus (IFOF). The simple mediation model revealed that the mean MD value of forceps minor and right IFOF, the mean FA value of the left CST and right IFOF, and the mean RD value of the left CST, SLF and right IFOF partially mediated the correlations between the CSVD burden and multiple cognitive scores. CONCLUSIONS:Our findings offer potential neuroimaging targets for intervening in and improving cognitive dysfunction in patients with different CSVD burdens.

BACKGROUND:Cerebral small vessel disease (CSVD) causes cortical atrophy and motor decline, but the specific cortical regions involved and their mediating role remain unclear. We aimed to determine whether regional cortical thickness mediates the association between CSVD severity and motor function. METHODS AND MATERIALS:We recruited 354 participants with CSVD (mean age 57.2 ± 11.4 years), of whom 55 had 16-month follow-up. Participants underwent 3.0 T MRI with 3D T1-weighted MPRAGE (1 mm3 isotropic) and motor testing (TUG and 3-m walk test). Cortical thickness was quantified using FreeSurfer v6.0 with longitudinal processing for follow-up scans. General linear models tested cross-sectional associations, linear mixed-effects models examined longitudinal effects, and mediation analysis assessed indirect effects. RESULTS:Significant negative associations were observed between cortical thickness and CSVD severity in the right insula, left rostral anterior cingulate cortex, and left lateral occipital cortex. Additionally, significant associations were found between cortical thickness at multiple time points in the right insula (β = 0.594, P = 0.024) and TUG test scores. The thickness of the right insular cortex mediated the relationship between CSVD severity and TUG performance (mean [SE] indirect effect, 0.085 [0.045]; 95 % CI, 0.015-0.197). CONCLUSIONS:CSVD severity was associated with cortical thinning in specific cortical regions, and right insular cortical thickness levels were related to motor performance and partially mediated the association between CSVD severity and mobility impairment. ETHICS APPROVAL AND CONSENT TO PARTICIPATE:All study procedures were approved by the Ethical Committee of the Institutional Review Board (IRB) of the Shandong Institute of Medical Imaging (2019-002). The study was conducted in accordance with the Declaration of Helsinki. All participants signed an informed consent form before the commencement of the study.

INTRODUCTION:Cerebral small vessel disease (CSVD) is a common neurological disorder with limited pathology on conventional magnetic resonance imaging. This study uses quantitative susceptibility mapping (QSM) to investigate links among brain iron, plasma neurodegenerative proteins, and cognition in CSVD. METHODS:This study enrolled 319 CSVD patients, grouped into CSVD-M and CSVD-S. Plasma proteins were measured in 178 participants, with 80 being followed up after 2 years. QSM-based voxel-wise analysis assessed brain iron, CSVD severity, and protein correlations. A cross-lagged panel model was used to analyze the temporal association between plasma protein levels and brain iron levels. RESULTS:In CSVD-S, elevated QSM values in the right Rolandic operculum/superior temporal gyrus negatively correlated with plasma Aβ42 and executive function. Aβ42 also negatively correlated with QSM in cortical regions, tied to episodic memory decline. Higher baseline Aβ40 predicted increased QSM in the left putamen at follow-up. DISCUSSION:Plasma Aβ42 and Aβ40 may drive brain iron deposition and cognitive impairment in CSVD, serving as potential early biomarkers for disease progression. HIGHLIGHTS:QSM reveals brain iron links to Aβ42, cognition in CSVD. Plasma Aβ42 correlates with iron in motor and frontal areas. High Aβ40 predicts putamen iron increase in CSVD follow-up. Iron deposition is tied to executive, memory deficits in CSVD.

AIMS:We aimed to specify relationships among cerebral small vessel disease (CSVD) burden, cognitive dysfunction, and brain structure-function coupling changes. METHODS:A total of 108 patients with mild CSVD burden (CSVD-m), 53 patients with severe CSVD burden (CSVD-s), and 76 healthy controls (HC) were included in this study. The ratio of regional homogeneity (ReHo) or amplitude of low-frequency fluctuation (ALFF) to gray matter volume (GMV) was calculated as an indicator of voxel-wise structure-function coupling. RESULTS:Significantly decreased or increased ReHo-GMV and ALFF-GMV coupling values in patients with severe CSVD burden were primarily found in several brain regions, and the disrupted structure-function coupling in the right putamen mediated the relationship between CSVD burden and cognitive dysfunction. CONCLUSIONS:Brain structure-function coupling characterized by ReHo-GMV and ALFF-GMV mediated the cognitive dysfunction caused by CSVD and was an innovative and effective brain imaging indicator for exploring the association between CSVD burden and cognitive dysfunction.

NiFe LDHs/MXene composites are preliminarily prepared by the hydrothermal method. Then, Ni nanoparticles/ LDHs/MXene ternary composites are formed by in-situ reduction by NaBH4 in liquid phase. Interfacial morphology and structure of Ni/LDHs/MXene composites are investigated by SEM, XRD, and XPS. For catalytic hydrogenation of p-nitrophenol (4-NP), the catalytic apparent rate (Kapp) of Ni/LDHs/MXene-4 sample can reach to 175.5 s-1 center dot g-1 and the actual conversion rate is close to 100% after 9 min. As a recyclable catalyst, the stability of catalytic hydrogenation can remain about 94.1 % after 7 cycles. These ternary composites may be potentially applied in the pharmaceutical intermediates and catalytic conversion.

INTRODUCTION:Cerebral small vessel disease (CSVD) contributes to cognitive decline, yet the impact of white matter hyperintensity (WMH) distribution and plasma amyloid beta (Aβ) on thalamic subregions remains unclear. METHODS:In this prospective study, 175 patients with CSVD and matched controls underwent high-resolution magnetic resonance imaging (MRI), plasma biomarker assessment, and cognitive testing. WMHs were segmented and categorized by spatial patterns. Thalamic subregions were parcellated using the THalamus Optimized Multi-Atlas Segmentation (THOMAS) framework. Mixed-effects models evaluated the longitudinal effects of WMH progression and plasma Aβ on thalamic subregional volumes. RESULTS:CSVD patients exhibited selective atrophy in left medial geniculate nucleus (MGN), mediodorsal-parafascicular (MD-Pf), and lateral geniculate nucleus (LGN), with volumes associated with processing speed and attentional control. Thalamic and basal ganglia WMH burden significantly predicted subregional atrophy. In CSVD, WMH progression dominated longitudinal thalamic degeneration. DISCUSSION:Distinct WMH spatial patterns and vascular factors drive thalamic subregional atrophy in CSVD, contributing to cognitive decline. HIGHLIGHTS:Patients with cerebral small vessel disease (CSVD) exhibit selective atrophy in thalamic subregions compared to healthy controls (HCs). Thalamic white matter hyperintensity (WMH) burden strongly predicts mediodorsal-parafascicular and lateral geniculate nucleus atrophy in patients with CSVD. Plasma amyloid beta dynamics differentially influence thalamic integrity in CSVD compared to HCs.