Fancourt D, Finn S, Mak HW
… +2 more, Steptoe A, Bloomberg M
Ann N Y Acad Sci
· 2026 Mar · PMID 41842589
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Cultural engagement (e.g., going to live music events and theater performances, museums, galleries and exhibitions, and the cinema) is longitudinally associated in repeated epidemiological studies with age-related mental...Cultural engagement (e.g., going to live music events and theater performances, museums, galleries and exhibitions, and the cinema) is longitudinally associated in repeated epidemiological studies with age-related mental and physical health outcomes. However, it is unclear whether it also influences how fast older adults age physiologically-so-called age acceleration. This study aimed to ascertain whether regular cultural engagement among older adults is related to slower physiological aging using a previously derived physiological age index and a doubly robust estimation approach to account for confounders. Using older adults from the English Longitudinal Study of Ageing (n = 4467), we found that cultural engagement was related to lower physiological age cross-sectionally (average treatment effect -2.17; 95% CI -3.48 to -0.86) and 4 and 8 years later. The effect was seen consistently for all three types of cultural activity explored (cultural performances, museums/exhibitions, and the cinema). These analyses were robust to multiple sensitivity analyses, including considering alternative confounding structures, outliers, and treatment specification. Overall, these findings provide insight into how cultural engagement may be related to processes of aging.
Ann N Y Acad Sci
· 2026 Mar · PMID 41842587
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Accurate kidney tumor segmentation is critical for surgical planning but is challenged by indistinct boundaries and high morphological variability in computed tomography (CT) images. We propose the adaptive boundary-awar...Accurate kidney tumor segmentation is critical for surgical planning but is challenged by indistinct boundaries and high morphological variability in computed tomography (CT) images. We propose the adaptive boundary-aware network (MABS-Net). The architecture integrates three core innovations: (1) a boundary-aware multiscale feature extraction module using learnable boundary-enhancing convolutions and adaptive weight maps to capture subtle edge cues; (2) an adaptive three-stage cascaded strategy for progressive refinement from coarse localization to uncertainty-driven boundary optimization; and (3) a contrastive learning mechanism with online hard example mining to explicitly boost feature discrimination between tumor and normal tissues in ambiguous regions. Experiments on the KiTS19 and KiTS21 datasets demonstrate MABS-Net's superiority. On KiTS19, it achieved a Dice coefficient of 0.891 ± 0.034, significantly outperforming the nnU-Net baseline. Notably, the 95% Hausdorff distance (HD95) was reduced to 6.73 ± 2.28 mm, and the boundary Dice score improved by 5.8% compared to state-of-the-art methods, validating our boundary-aware design. Furthermore, the model provides pixel-wise uncertainty maps to support reliable clinical decision-making. MABS-Net balances high accuracy with computational efficiency (0.53 s/case), presenting a promising solution for automated renal tumor analysis.
Ann N Y Acad Sci
· 2026 Mar · PMID 41837587
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Sepsis-associated intestinal dysfunction (SAID) drives multiorgan failure through dysregulated autophagy-inflammation crosstalk, for which effective therapies remain limited. This review systematically delineates SAID pa...Sepsis-associated intestinal dysfunction (SAID) drives multiorgan failure through dysregulated autophagy-inflammation crosstalk, for which effective therapies remain limited. This review systematically delineates SAID pathophysiology, evaluates preclinical and clinical evidence for autophagy-targeted interventions, and explores emerging intestinal-specific therapeutic targets. Autophagy preserves intestinal barrier integrity by clearing damaged organelles and suppressing NLRP3 inflammasome activation, whereas inflammatory mediators such as TNF-α/IL-6 and reactive oxygen species impair autophagic flux via Beclin-1 destabilization and lysosomal dysfunction, establishing a pathogenic vicious cycle. Preclinical evidence demonstrates that rapamycin and TFEB agonists enhance autophagy, while ATG5 overexpression and NLRP3 siRNA restore epithelial homeostasis. Clinically, IL-1 receptor antagonists have demonstrated efficacy in specific sepsis subpopulations. Stage-specific therapeutic optimization is essential, as interventions must be tailored to the hyperinflammatory versus immunoparalysis phases. Novel intestinal-barrier-specific targets-including aquaporin-3 (AQP3), ghrelin, and Nur77-emerge as key regulators of the autophagy-inflammation axis and represent promising therapeutic candidates. Targeting autophagy-inflammation crosstalk holds significant therapeutic potential, though clinical translation requires human-relevant models and precision medicine approaches to address disease heterogeneity and stage-specific pathophysiology.
Alkhatatbeh T, Alkhatatbeh A, Liao Y
… +4 more, Zhang Z, Fang H, Chen W, Zhang R
Ann N Y Acad Sci
· 2026 Mar · PMID 41830909
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Deep learning models for Kellgren-Lawrence (KL) grading often report optimistic performance due to data leakage and fail to generalize across institutions because of domain shift. To address this reproducibility crisis,...Deep learning models for Kellgren-Lawrence (KL) grading often report optimistic performance due to data leakage and fail to generalize across institutions because of domain shift. To address this reproducibility crisis, we introduce KL-FuseNet, a multitask architecture fusing global (ConvNeXt-Base) and local (ResNet-50) features to predict ordinal grades, label distributions, and binary severity (KL≥2). Using strict patient-wise stratified splits on an internal osteoarthritis initiative dataset (n = 8260) and an independent Chinese cohort (n = 2295), we compared zero-shot transfer against selective fine-tuning. KL-FuseNet achieved robust internal agreement (quadratic Cohen's kappa [QWK]: 0.881; accuracy: 70.3%). While external zero-shot deployment revealed a domain gap, with accuracy dropping to 66.1%, our selective fine-tuning protocol significantly bridged this divide, boosting external accuracy to 80.0% and QWK to 0.950, with an AUC of 0.984 for clinically significant osteoarthritis (KL≥2). These results demonstrate that while KL-FuseNet achieves state-of-the-art performance under rigorous evaluation, domain-aware adaptation is essential for clinical utility. This study establishes a reproducible pathway for deploying automated grading models across heterogeneous medical centers.
Wang C, Xia J, Li P
… +4 more, Feng X, Yang L, Lu Z, Wang W
Ann N Y Acad Sci
· 2026 Mar · PMID 41824790
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Primary dysmenorrhea (PDM) is a prevalent gynecological disorder in young females, with limited treatment options despite its high prevalence and detrimental effects. Transcutaneous auricular vagus nerve stimulation (taV...Primary dysmenorrhea (PDM) is a prevalent gynecological disorder in young females, with limited treatment options despite its high prevalence and detrimental effects. Transcutaneous auricular vagus nerve stimulation (taVNS) has shown promise in alleviating PDM symptoms, but its long-term efficacy and individual variability remain uncertain. In this study, we utilized a single-blind, sham-controlled experimental design to investigate the long-term effects of taVNS on PDM. Sixty women with PDM were randomly assigned to receive either real or sham taVNS for 10 consecutive days, and 30 age-matched healthy controls were selected for baseline electroencephalography (EEG) comparison. The effects of taVNS were assessed at the first, second, and sixth menstrual periods post-treatment. Baseline resting-state EEG microstates were used to examine individual differences in taVNS efficacy. Our results demonstrated that taVNS effectively alleviates PDM symptoms, with benefits lasting at least 6 months. Additionally, menstrual pain may be associated with abnormal brain microstates related to saliency (class C) and the switching and reorientation of attention (class D). These neural alterations may mediate the relationship between baseline menstrual symptom severity and interindividual variability in taVNS efficacy. Our study highlights the effectiveness of taVNS for PDM treatment and underscores the importance of baseline microstates in influencing individual treatment responses.
Lyu F, Ma Y, Zhao L
… +6 more, Guo G, Zhao Z, Wang Q, Lu H, Li C, Cao C
Ann N Y Acad Sci
· 2026 Mar · PMID 41824770
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Mining pipeline transportation systems often operate under partially filled conditions. Filling level variations induce circumferential asymmetry, modifying the pipe mass distribution and dynamic characteristics and inva...Mining pipeline transportation systems often operate under partially filled conditions. Filling level variations induce circumferential asymmetry, modifying the pipe mass distribution and dynamic characteristics and invalidating conventional axisymmetric vibration models. In particular, the mechanism of circumferential modal wavenumber coupling under partially filled conditions remains unclear. To investigate the vibration behavior of partially filled pipes, a bidirectional acoustic-structural coupled dynamic model for partially filled pipes was developed. We introduce an acoustic-pressure integral work formulation accounting for filling volume variations to quantify the fluid-structure coupling. Based on this framework, wavenumber-frequency, harmonic response, and modal shape analyses are combined to investigate the effects of filling level on circumferential modal wavenumber coupling and frequency response characteristics. The model was validated through impact hammer experiments on water- and coal-slime-filled pipes. The results demonstrate that asymmetric mass distribution induced by partial filling is the primary mechanism responsible for circumferential modal wavenumber coupling. Under empty and fully filled conditions, the system remains approximately axisymmetric, and the vibration response is dominated by a single circumferential wavenumber. At intermediate filling levels, circumferential symmetry is broken, leading to multimodal wavenumber participation, splitting of degenerate modes, additional resonance peaks, and an upward shift in modal frequencies.
Xiao Y, Jiang Q, Qian Y
… +6 more, Shi J, Zhang H, Kennedy CR, Li G, Jiang F, Rozelle S
Ann N Y Acad Sci
· 2026 Mar · PMID 41823477
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Mental health symptoms are common among caregivers of young children in low-resource settings, yet access to psychological care remains limited due to shortages of specialists, low awareness, and stigma. This qualitative...Mental health symptoms are common among caregivers of young children in low-resource settings, yet access to psychological care remains limited due to shortages of specialists, low awareness, and stigma. This qualitative study explored the acceptability and appropriateness of delivering a postnatal mental health intervention for mothers through community and township health centers (CTHCs) in Shanghai, China. We conducted in-depth interviews with 50 mothers of children under 3 years of age, recruited from nine CTHCs and one parenting center, including both those with and without depressive symptoms. Data were analyzed using a rapid analysis approach to identify themes related to perceived values, burdens, motivations, and barriers to participation. Mothers valued interventions that aligned with their personal needs, addressed both parenting knowledge and mental health, offered emotional and social support, and involved family members. Key barriers included time constraints, childcare responsibilities, stigma toward mental health, and accessibility of the location of the intervention. Flexible delivery formats and modes, integration with routine child health services, and nonstigmatizing framing were identified as potential strategies to enhance engagement.
Hou Z, Han J, Wu S
… +3 more, Wang Z, Zhang M, Xu D
Ann N Y Acad Sci
· 2026 Mar · PMID 41817512
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Self-supervised learning (SSL) can capture intrinsic features from extensive unlabeled data, significantly reducing dependence on labels and performing well in human activity recognition (HAR). However, existing SSL fram...Self-supervised learning (SSL) can capture intrinsic features from extensive unlabeled data, significantly reducing dependence on labels and performing well in human activity recognition (HAR). However, existing SSL frameworks depend excessively on data augmentation paradigms, and often mistakenly treat noise as learning objectives during mask reconstruction. Moreover, the data set scale often constrains accuracy and hinders real-world applicability. To address these issues, this paper proposes a new SSL objective that integrates an attention mechanism with an adaptive time series mixer. Without relying on data augmentation, the proposed model assigns lower weights to noise for capturing the global dependencies and extracting the local feature within inertial measurement unit (IMU) series. The proposed model was validated through comprehensive evaluations of three public data sets (UCI, Motion, and HHAR) and one self-collected data set (named CQJTU-FCE). The experimental results fully demonstrate that, on the self-collected data set, the proposed model achieves an average improvement of 6.54%, 8.55%, and 7.88% in accuracy, F1 score, and Cohen's kappa coefficient, respectively, compared with the baseline models. Similarly, on the public data sets, the average enhancements reached 10.63%, 11.77%, and 13.39% across the same evaluation metrics. These results confirm the generalizability of the model to various data sets, offering a more efficient and reliable solution for HAR tasks.
Ann N Y Acad Sci
· 2026 Mar · PMID 41817469
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Courtship is often viewed as a linear process where males display and female assessment of this display shapes her mating decisions. However, communication can be far more dynamic and interactive, particularly in species...Courtship is often viewed as a linear process where males display and female assessment of this display shapes her mating decisions. However, communication can be far more dynamic and interactive, particularly in species that develop long-term relationships. Interactional complexity is not well captured by traditional models of animal communication. Here, we tested whether interactional elements shape female preferences in the monogamous zebra finch. We used selective calling as a measure of female preference. First, we asked whether females' most-preferred song (based on passive song playback) matched her most-preferred male (based on a live interaction). We found a mismatch in the preferences for song versus live males, and female preferences for a live male did not appear to be linked to how much he sang. Next, to experimentally manipulate male responsiveness, we habituated females to the song of their most-preferred or least-preferred male. This song habituation caused females to change their preferences differently depending on whether they were habituated to their most- or least-preferred male. Together, these results highlight that additional interactional elements, beyond male song, impact female social preferences. More broadly, our results contribute to growing evidence that models of communication should incorporate interactional and distributed elements.
Ann N Y Acad Sci
· 2026 Mar · PMID 41817462
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Deep neural networks are driving the iterative advancement of magnetoencephalography (MEG) decoding models. While explainable artificial intelligence, particularly traditional post-hoc feature attribution approaches, has...Deep neural networks are driving the iterative advancement of magnetoencephalography (MEG) decoding models. While explainable artificial intelligence, particularly traditional post-hoc feature attribution approaches, has made significant progress in interpreting the prediction mechanisms of individual models, a critical gap remains in understanding the differences in decision logic between various models, known as model differencing. By facilitating model selection, optimization updates, and practical applications such as error pattern analysis and decision fusion, this approach demonstrates significant research and application potential. However, existing approaches face fundamental limitations: insufficient accuracy in differencing measurements, often relying on binary simplification, and deficient localization of differencing decision boundaries, typically constrained to low-dimensional spaces. To address these challenges, we propose a rule-based MEG model differencing approach called boundary-optimized rules via predict-probability difference (BO-RPPD). Key innovations include (1) a novel measurement based on predict-probability differences between dual models, enabling the direct learning of differencing rules, and (2) integrated counterfactual generation and feature reduction to guide the exploration of optimal predict-probability difference boundaries, especially within low-sample, high-dimensional MEG feature spaces. Experiments on two MEG datasets demonstrate the overall superiority of our proposed approach: prediction performance significantly outperforms all benchmarks, achieving up to a 24% improvement in F1-score and effectively covering broader samples. The number of generated rules matches the optimal benchmark, ensuring strong explainability. The approach shows practical value in error pattern analysis and decision fusion. Model-agnostic, our approach generalizes effectively to electroencephalography (EEG) and structured datasets.
Cable J, Giuli R, Fox MR
… +36 more, Rosen RL, Valdovinos-García LR, Siboni S, Clarke JO, Johnston N, Samuels TL, Scarpignato C, Stein EM, Fass R, Remes-Troche JM, Khan A, Rahman AK, Lynch K, Jodorkovsky D, Vela MF, Vandenberg A, Kuo B, Ergun P, Jirapinyo P, Asti E, Tolone S, Sheu EG, Salvador R, Sozzi M, Husain IA, Wu JC, Hobson A, Sharma NS, Lo WK, Duncan DR, Gyawali CP, Chan WW, Sifrim D, Savarino E, de Bortoli N, Rogers BD
Ann N Y Acad Sci
· 2026 Mar · PMID 41817458
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Recent advances in the diagnosis and management of reflux disease were the central focus of the inaugural Gatherings in Esophagology (GiE), which convened experts across gastroenterology, surgery, otolaryngology, pulmono...Recent advances in the diagnosis and management of reflux disease were the central focus of the inaugural Gatherings in Esophagology (GiE), which convened experts across gastroenterology, surgery, otolaryngology, pulmonology, and basic research. The sessions highlighted innovations in reflux monitoring-including high-resolution manometry, wireless pH monitoring, and novel salivary biomarkers-while critically evaluating their diagnostic accuracy and clinical utility. Presentations explored the limitations of traditional proton-pump inhibitor therapy, the emergence of potassium-competitive acid blockers as a new class of acid suppressants, and the evolving role of adjunctive treatments such as mucosal protectants, reflux reducers, and neuromodulators for refractory symptoms. The discourse extended to advanced interventional procedures, including transoral incisionless fundoplication, magnetic sphincter augmentation, and the RefluxStop device, with discussion of patient selection, efficacy, and complication management. Discussants emphasized the pathophysiology and management of extraesophageal manifestations of reflux, the interplay between reflux and pulmonary disease, and the diagnostic challenges in pediatric populations. The meeting also addressed the integration of behavioral therapies, the role of the microbiome, and the application of artificial intelligence in reflux diagnostics. Collectively, these insights underscore a shift toward precision medicine in reflux disease, emphasizing individualized diagnostic strategies and tailored therapeutic approaches to improve patient outcomes.
Chai H, Liao W, Wu H
… +5 more, Han C, Chen J, Liu D, Dai B, Liu X
Ann N Y Acad Sci
· 2026 Mar · PMID 41806135
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In buildings, steel-concrete composite beams with web openings save service space but weaken structural performance. To address this issue, this study proposes the use of a perfobond strip (PBL) connector in the opening...In buildings, steel-concrete composite beams with web openings save service space but weaken structural performance. To address this issue, this study proposes the use of a perfobond strip (PBL) connector in the opening area to compensate for the loss of connection performance and composite action caused by the web openings. A total of 25 specimens were subjected to experimental testing and finite element simulation to investigate the effects of 11 varying parameters-including connector type, hole radius of the perforated plate, hole position, and the diameter of through reinforcement-on the mechanical performance and composite behavior of the specimens. The results indicate that, compared to traditional stud connectors, PBL connectors increase the shear force transferred into the concrete by 13.57%-18.33%, thereby enhancing the structure's shear resistance. Specimens with PBL connectors in the opening area exhibited favorable ductile failure characteristics and improved shear capacity, with failure modes transitioning to concrete flange splitting and rebar shearing. Among the parameters studied, increasing the hole radius of the PBL plate resulted in the greatest load-bearing capacity, while increasing the diameter of the penetrating rebars most effectively reduced the relative slip behavior of the specimens.
Chadda KR, Routh J, Ismail T
… +8 more, Amirthalingam SD, Angkurawaranon C, Boonyaratanakornkit V, Zuraina D, Norlida D, Lukas S, Said A, Jeevaratnam K
Ann N Y Acad Sci
· 2026 Mar · PMID 41793302
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This study investigated what value health professional students and staff place on employability and global mobility training. It investigated the most important employability and global mobility characteristics, and how...This study investigated what value health professional students and staff place on employability and global mobility training. It investigated the most important employability and global mobility characteristics, and how perceptions vary between students and academics. The study used an anonymous, online questionnaire distributed to health professional students and academic staff at the University of Surrey (UK) and the University of Malaysia, Sarawak (Malaysia). The outcomes of pairwise comparison questions were processed using the Elo algorithm to generate importance rankings of the employability and global mobility characteristics. One hundred and forty-two students and 42 academics were included. The most important employability and global mobility characteristics were an ability to get along with people from different cultural backgrounds, adaptability, openness to new experiences, an ability to read situations and respond to them, communication skills, and problem-solving. The characteristics that were ranked highly by academics were also likely to have high rankings by students. This study demonstrates that students and academics value employability and global mobility teaching and give similar ratings to specific characteristics. The next step is to investigate how these characteristics can be incorporated into higher education curricula and adapted over time in response to evolving workforce requirements.
Ann N Y Acad Sci
· 2026 Mar · PMID 41774414
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Group synchrony in the animal kingdom is usually associated with mating. Being in sync is likely advantageous, as it may help in luring the opposite sex. Yet there are also disadvantages-such as the homogenization of the...Group synchrony in the animal kingdom is usually associated with mating. Being in sync is likely advantageous, as it may help in luring the opposite sex. Yet there are also disadvantages-such as the homogenization of the group-which make it harder for individuals to stand-out. Here we address this trade-off, bringing together the Kuramoto model with concepts from evolutionary game theory. We focus on the existence of self-interested cheaters, which have been extensively studied in a variety of species. In our scenario, cheating individuals take part in the synchronous group display but position themselves (in terms of phase) slightly ahead of or behind the pack. This allows them to enjoy both the group benefit of advertisement and the individual benefit of being unique. But a group can only tolerate a limited number of such individuals while still achieving synchrony. We therefore incorporate a form of policing into our model: If an individual strays too far form the group's synchronous phase, they reveal themselves as dishonest and are punished. Our model offers testable predictions regarding natural population compositions, and will hopefully spur further investigation into not only how, but also why, natural systems synchronize.
Wang YL, Lin HC, Chen JT
… +4 more, Chang HH, Hsieh TF, Hung HY, Wang SK
Ann N Y Acad Sci
· 2026 Mar · PMID 41774401
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DLX3 is a homeobox transcription factor essential for multiple organogenesis processes. Mutations in DLX3 cause trichodentoosseous syndrome (TDO), characterized by curly hair, sclerotic bone, enamel, and dentin defects a...DLX3 is a homeobox transcription factor essential for multiple organogenesis processes. Mutations in DLX3 cause trichodentoosseous syndrome (TDO), characterized by curly hair, sclerotic bone, enamel, and dentin defects as well as taurodontism. Phenotypic variability in TDO has been well documented, but its pathogenesis remains poorly understood. Here, we characterized three TDO families with distinct clinical features and identified a known DLX3 deletion (c.561_562del) and the first pathogenic splice-site variant (c.516+1_516+2insA). The proband with the splice-site mutation displayed a mesenchymal-dominant phenotype with severe dentin hypoplasia, enlarged pulp chambers, and hypertaurodontism but nearly normal enamel, whereas the mother and sister showed epithelial-dominant anomalies, including enamel hypoplasia and kinky hair. Minigene analysis demonstrated that c.516+1_516+2insA generated two aberrant transcripts encoding p.Val173Aspfs*28 and p.Arg120_Val173del. These mutant proteins localized mainly in the cytoplasm and showed markedly reduced transactivation activity. In cultured human dental pulp cells, DLX3 overexpression upregulated the odontoblastic markers DSPP, MMP20, and WNT10A. Chromatin immunoprecipitation and reporter assays further revealed that DLX3 directly activates WNT10A via a conserved enhancer (chr2:218,878,973_218,879,302) and three upstream binding sites. These findings expand the TDO mutational spectrum and suggest that differential mutant DLX3 expression may contribute to phenotypic variability, whereas disrupted regulation of WNT10A underlies dentin defects and taurodontism.
Ann N Y Acad Sci
· 2026 Mar · PMID 41774098
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We conducted a comprehensive first-principles investigation of the electronic structure, photoresponse, mechanical, and thermodynamic characteristics of the newly synthesized compound tetragonal-VN using density function...We conducted a comprehensive first-principles investigation of the electronic structure, photoresponse, mechanical, and thermodynamic characteristics of the newly synthesized compound tetragonal-VN using density functional theory. The calculated lattice parameters closely align with both experimental and theoretical data. Electronic structure analysis reveals that VN exhibits metallic conductivity, with significant hybridization between V-3d and N-2p states, indicating strong covalent bonding. VN demonstrates isotropic optical properties, with a high static dielectric constant (56.9), notable reflectivity (59% at 0 eV), and significant absorption in the ultraviolet-visible range. It is mechanically stable, exhibits a degree of elastic anisotropy, and possesses a brittle nature. VN has a Vickers hardness of 26.2 GPa, approximately three times greater than that of VN, suggesting that it is suitable for use in wear-resistant coatings and cutting tools. From a thermodynamic perspective, VN is characterized by a high Debye temperature (1023.5 K) and significant lattice thermal conductivity (59.8 W·m ·K ). Its melting temperature, which exceeds 3177 K, distinguishes it as a promising candidate for applications that require extreme temperatures. These findings establish a strong foundation for the future applications of VN in advanced materials science, particularly in high-performance coatings and photonic devices.
Sun R, Qin H, Zhang W
… +6 more, Guo X, Teng Y, Xu M, Liu J, Ning Z, Wang A
Ann N Y Acad Sci
· 2026 Mar · PMID 41774091
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Metabolic reprogramming, particularly the dysregulation of cholesterol metabolism, is a hallmark of pancreatic ductal adenocarcinoma (PDAC). However, the underlying molecular drivers remain largely elusive. In this study...Metabolic reprogramming, particularly the dysregulation of cholesterol metabolism, is a hallmark of pancreatic ductal adenocarcinoma (PDAC). However, the underlying molecular drivers remain largely elusive. In this study, we demonstrate that Tribbles homolog 1 (TRIB1) is elevated in PDAC tissues and is significantly associated with poor prognosis. Functionally, TRIB1 mRNA knockdown suppresses PDAC cell growth and tumor formation, while its overexpression promotes both. Mechanistically, TRIB1 protein binds to the DNA-binding domain of PPARγ and inhibits its transcriptional activity. This interaction relieves the PPARγ-mediated repression of HMGCR, the rate-limiting enzyme in the mevalonate pathway, thereby fueling de novo cholesterol biosynthesis. Furthermore, in vivo experiments indicate that PDAC tumors with high TRIB1 expression were more sensitive to the HMGCR inhibitor atorvastatin. Collectively, our findings highlight the critical role of the TRIB1-PPARγ-HMGCR axis in the metabolic rewiring of PDAC and suggest that TRIB1 may serve as a predictive biomarker for optimizing statin-based metabolic therapies.